Category Archives: Texas Stem Cells

Last week, the Mens Health Films video team descended upon my home in Spokane, Washington to film me on my home turf doing what I do.

So for your education and entertainment, below is the madness that ensued, along with helpful timestamps, descriptions and links below the video.

1:40: You see me screaming, grunting and groaning using a special force plate and isometric training bar setup(this is the same single set to failure style of training I mentioned on this Joe Rogan episode). Using this approach, you can get hella strong with a single 12-15 minute workout performed twice a week. For example:

A Workout is all pushes: -Bench Press-Tricep Press-Shoulder Press-Leg Press-Calf Press

B workout is all pulls:-Bicep Curl-Ab Crunch-Lat Pull Down-Deadlift-Shoulder Shrug

Have fun. This style of isometric training, which I perform on a machine called aPeakFitPro, is hard as hell but blasts strength, growth hormone and peak force production capacity through the roof, with extremely low risk of injury.If you want one of these bad boys for your own home gym, health club, etc. you can click here and use code greenfield to save $100.

2:39: Before one of my isometric sets, you see me taking a big whiff of smelling salts.Long story short is that one big sniff of these ammonia based salts makes you want to fight someone, kill something, punch your fist through the wall, never drink a cup of coffee again, or lift very heavy things.Along with the peppermint trick I mention here, its one of the more potent ways to jack up your sympathetic fight and flight nervous system for pennies on the dollar. The stuff I use isNose Tork Smelling Saltsand it is basically like smelling salts on steroids.

3:51: I begin to inject stem cells extracted from my own fat and grown atU.S. Stem Cell Clinic (that link gives you a $500 discount on the same procedure I did). As of current laws, the adipose procedures using in enzyme digestion of your own fat to concentrate stem cells are not illegal and do not require you to go out of the country (contrary to popular belief). Mesenchymal cells (MSCs) can be obtained from bone marrow or fat and those cells are similar from either source. The main difference is that the number of MSCs from fat is about 500x higher. Adipose also has a much higher population of CD34 protein and as a result is much more angiogenic (blood vessel growth inducing) compared to bone marrow. At the U.S. Stem Cell Clinic, they use an enzyme to break down the fat. The enzyme is collagenase and breaks collagen bonds in extracellular matrix outside all the cells. Basically the glue that holds the fat together gets broken down so you can spin fat in centrifuge. This allows the fat cells to go to the top because they are light in weight and stem cells and other cells go to bottom because they are heavy. Then voila! You inject (in this case, I self-injected but a physician friend, nurse practitioner, etc. could probably do it for you).

6:10: You see me doing my morning yoga, ELDOA, core foundation training, etc. inside my infrared sauna.If you have no clue about the difference between wet saunas, steam rooms, dry sauna, infrared sauna, niacin detox, how long to spend in the sauna, etc., etc., then Id highly recommend you read my article Three Ways To Biohack A Sauna For More Heat, A Better Detox & Enhanced Fitness. FranklyIm addicted to my sauna, as I delve into here on the science of saunas, I feel amazing when I wander out of daily, blood-building, nitric-oxide boosting sauna session. Then, once I follow up the sauna with a cold shower or a dip into the cold pool back behind my house in the forest, I feel freaking unstoppable the rest of the day. You can use code BEN to save $450 on the same massive walk-inClearlight Infrared SaunaI own.

6:45: I hold up my first work of fiction: a book called The Forest. The official version wont be released until this summer, but you can read a beta-version for free here.Upon stepping into a dark shed in the middle of the forest, twin brothers River and Terran are transported to a remote prison island in another world crawling with strong magic, hidden snares, and rogue creatures. Using their powers to control the elements of water and earth, they fight their way from the island, only to discover an entire world sieged by evil shramana and vile serpents. Can two human boys save this otherworld? Can the seafarers, elves, warrior princesses, healers and magisters they meet along the way help them in the battle? Will the chaotic struggles they encounter follow them back into their own world? Youll find out in this riveting adventure that includes harsh wilderness, epic battles, tangled romances, elemental sciences and hardcore survival. Like Lord Of The Rings or Chronicles Of Narnia, I wrote this fantasy fiction for all ages, and it is the first in a five-book series I plan to write over the next several years.

6:48: You see me breathing a special form of humidified air from a strange-looking blue, bubbling device called an Eng3 NanoVi. The video hereexplains how NanoVi generates a bio-identical signal mimics the good reactive oxygen species your body naturally produces and this assists a multi-step process of reinstalling protein functions that are essential to cellular activity. Basically, it repairs DNA as you simply sit there breathing the water in through a nasal cannula or through your mouth. It is based on the concept that breathing in good reactive oxygen species (ROSs) causing a steep upregulation of cellular repair. Its especially good to repair the damage from free radicals in athletes who exercise frequently.

6:58: I take one of my flagship supplements: essential amino acids.I am at the point now to where I take two doses of 10-20 grams of these essential amino acidsper daytostimulate faster muscle growth, recover more rapidly from exercise, become more resistant to fatigue during a grueling workout, or just benefit from additional amino acids in their most absorbable form to support calorie restriction, fasting and ketosis. Essential amino acids are just that: essential. Your body cant produce them on its own and yet they are crucial for supporting and maintaining the muscular, skeletal, enzymatic, nervous and hormonal systems of the body. Your body generally gets amino acids from the protein you consume as food. But your bodys amino acid utilization from common protein sources is often less than 50% of their content, with the rest being excess calories and waste. About 48% of egg protein is utilized by your body, less than 32% for meat, poultry and fish, less than 18% of whey and soy protein, and only 1% of branched chain amino acids are utilized by the body. The amino acid utilization of essential amino acids is a whopping 99%, meaning your body is actually absorbing and utilizing the essential amino acids it needs. Dont take me wrong: of course, Im all about eating high-quality, nutrient-dense, tasty foods like steak, eggs, and nuts, but when youre in a situation that requires you get your protein fast and you get it absorbed even faster,Kion Aminos is my go-to solution (and heres a list of the other supplements that I use).

7:00: I mentionNAD (nicotinamide adenine dinucleotide).As I discuss in this comprehensive podcast interview on NAD,Scientific American publishedthe article Beyond Resveratrol: The Anti-Aging NAD Fad, an article that proposes that recent research suggests it may be possible to reverse mitochondrial decay (e.g. achieve a pretty potent anti-aging effect) with dietary supplements that increase cellular levels of a molecule called NAD, and also that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of NAD injections. The NAD injection clinic in San Diego (I interview them here) can set you up with patches, IVs, intranasal spray and a host of other ways to mainline the stuff into your system, or, as I discuss here, you can make precursors to NAD for pennies on the dollar with Pau D Arco bark tea.

7:02: I take a shot of lignite extract one of the few supplements my entire family takes regularly. In the podcast Why You Cant Get Away From The Toxin Glyphosate (& What You Can Do About It). I explain how this relatively new compound extracted from soil (termed lignite) protects the lining of the gut from the ravages of glyphosate, a nasty molecule which you find just about everywhere these days, even if you eat organic. You can find it on Amazon here, or at theRestore website you can use code BEN15 to save 15%.

7:10: I snort intranasalintranasal oxytocin spray.Oxytocin has been on a joy ride for 20 years, ever since animal studies first linked this hormone to bonding between mother and newborn, as well as between mating adults (you release boatloads of the stuff when you orgasm, and smaller amounts when you hug, engage in physical affection, etc.). Dubbed the cuddle or love hormone, more recently it has earned attention for its role in promoting trust (hence it is often marketed as liquid trust). Research does link it to increased trust, social bonding and even a predisposition to donate to charity, but also to allay social anxiety disorder, address autism, and decrease inflammation. It puts you in a pretty good, trusting mood, so just dont snort it before you go negotiate to get a deal on a car or buy a house. 😉

7:18: You see me bathing in the glorious red light and infrared rays produced a massive infrared LEDlight panel in my office. How does red light therapy work? Once absorbed into your body, red light energy gets converted into cellular energy, which kicks of a series of metabolic events such as the formation of new capillaries, elevated production of collagen, and the release of ATP. Red light therapy has been approved by the FDA and its effectiveness has been studied throughout the world. The wavelength of your red light device matters greatly, so you must, must, must pay attention to wavelength and delivered energy (the bulk of evidence suggests that 660-680 nm is the most effective).To get a big ol red light for yourself, you can click here and use code BEN save $25 on the same one I use (called a JOOVV (and yes, to increase testosterone as I discuss here I really do get naked and bathe my balls in red light for about 5-20 minutes a day)

7:22: Ive got a Vielightnasal probe stuck up my nose. If youre not familiar with the term photomedicine, then you will be soon, because one of the most cutting-edge features of the future of medicine and performance-enhancing biohacking involves the use of light and lightwaves (also known as photobiomodulation) for everything from nitric oxide release for physical and mental performance, to amplifying blood flow to the brain, to enhancing cognitive, muscular and mental performance, to building new red blood cells and optimizing oxygenation and far, far more. Intranasal light therapy and cranial light therapy, which I covered in the podcast How To Use Low Level Light Therapy and Intranasal Light Therapy For Athletic Performance, Cognitive Enhancement & More is based on light stimulation of blood capillaries in the nasal cavity and head. It has been used for the past several years in the medical industry as a very non-invasive method to introduce therapeutic light energy into the human body, and theres actually a surprising amount of research on this form of non-ionizing radiation on biological systems, including effects on cognitive performance, fighting free radicals, combatting Alzheimers symptoms and more. If you want one of these sexy looking space helmets or nasal probes for yourself, you can click here and use code GREENFIELD to save 10%.

7:24: I mentionrosemary essential oil for a cognition boost. Rosemary (along with peppermint and cinnamon) oil is not only fantastic to diffuse in your office or gym for a mental pick-me-up, but is also great for memory and for training your brain to go into performance mode when it detects the unique scent. I currently use this diffuser, and because essential oil tends to be oxidized, impure, or watered down with cheap fillers or additional oils, Im also pretty careful about which brand I use. You can click here to peruse the oils I like.

7:34: My giant, cereal-box-esqueOura Ringappears. Because it contains a tiny, built-in computer, this ring, unlike other self-quantification devices like a Fitbit or Jawbone, can be placed into airplane mode so that any bluetooth or other irradiating signals are completely disabled. The ring measures everything Id ever want to know about my body, including temperature, heart rate, heart rate variability (HRV), steps, sleep cycles, sleep percentages, readiness to train, and a whole lot more. And yes, you can wear it while doing pull-ups, kettlebell swings, presses, etc. with no issues. You can use code GREENFIELDOURA to save $75 here on their newest models.

7:35: I am donning my ultra-stylishRe-Timer Glasses, which I use to deliver copious amounts of blue-green light to my eyes in the morning, which jumpstarts my circadian rhythm. Heres why: the information your body gets about existence or absence of light is received via light-sensitive receptor proteins in the eyes retina. These proteins are called opsins. Opsins convert the photonicenergy of light into electrical potential in neurons, and project signals from light to the brains biological clock, as well as to other brain areas. This then increases neurotransmitter signalling and influences hormone production. Theselight-sensitive receptors are not only found in the retina, but also in many locations in yourbrain and body, such as the cerebrum, the hypothalamus, inside your ears and on every inch of your skin (which is why, by the way, its very important when you sleep in darkness at night to not just limit light exposure to your eyes, but also to your skin). Exercise, food, air, etc. all affect your bodys clock, but nothing beats light. When your eye senses light, it sends a signal to your brain to be awake.As it becomes dark in the evening, your body produces melatonin, telling your body it is time to sleep.The combination of biological processes in response to light and darkness are crucial factors for your body to remain synchronized and sleep at the right time. Morning bright light therapy can adjust your body clock to an earlier schedule through repeated exposure to bright light appropriately timed in the morning and evening bright light therapy (should you decide to wear glasses like this at night) canre-time your body clock to a later time by exposing you tobright light visual stimulation in the evening. Again, this all worksbecause light exposure is your bodysprimary cue to regulate yourbody clock. Anyways, you can read more about this concept at The Re-Timer Effect: How To Re-Time Your Circadian Rhythms If You Wake Up Too Early Or Stay Up Too Late. and you can get the glasses here and use codeBGF30 to save $30.

7:56: You may notice myBioMatin the background. This is a medical device that uses a computer control panel with an advanced IC chip manufactured by Texas Instruments, a polarized plug for power source protection, EMF interception tourmaline rocks for a negative ion boost, and amethyst crystals covering the entire surface area (yeah, yeah, I know I just took a deep dive into woo-woo land). The mat also produces deep-penetrating, far infrared rays along with negative ions. In other words, laying on this thing for 10-60 minutes a day, whether for a nap, a massage, a reading session, or meditation, can drastically reduce joint pain, improve sleep, decrease inflammation in tissue, soothe back pain, increase blood circulation and cause a host of other effects. Its like an expensive, adult version of a soothing blankie.

8:56: Im hanging like a crazy monkey from my yoga trapeze, which I use to decompress my spine a few times a day when I happen to pass by it (and yes, my gracious and lovely wife allows me to hang my trapeze directly next to the dining room table, which has made for some entertaining dinner party moments). Two weeks ago, I challenged myself to perform a full hour-long workout on the trapeze without dropping from it, and felt about two inches taller after hanging from it, squatting on it, doing rows, dips, pull-ups and just about anything else youd do from gymnastics rings on it, and also including some very, very deep hip flexor and psoas stretches. The trapeze I use is made byYoga Body. It hasnt failed me yet, meaning Ive not yet busted my head open on the dining room floor, so Ill vouch for its safety and toughness.

9:14: I glance at my Timex watch. I havent really mentioned this to many folks but, along with continuing to race for the Spartan pro teamI will be racing in professional obstacle course racing and triathlon for the world famous Team Timex this year.In the year 2000, Team Sports, Inc., an established professional cycling team management firm, sat down with the marketing team at Timex to create a first-of-its-kind, world class, triathlon team, with the mission of supporting athletes who strive to push the limits of the mind and body, and the Timex Multisport Team was born. Over 17 years have gone by and the passion and strength of the Timex Team is greater than ever. I used to race for this team back in my Ironman triathlon days, and now Im back, baby. Follow the Ben Greenfield Fitness calendar to see which races Ill be at (which will include the Wildflower triathlon and Malibu triathlon).

9:22: You see me with a blue mask on my face while working out on theLiveO2 adaptive contrast unit (save $300 with code BEN), which allows me to rapidly switch between breathing oxygen enriched air and hypoxic, oxygen void air that simulates over 10,000 feet of elevation. In one 15 minute workout, I can pump anywhere between 200-400% more dissolved oxygen into your blood plasma and the net effect of this workout lasts for several days. Its the equivalent of spending nearly an entire day in a hyperbaric oxygen therapy chamber, a strategy many folks in the anti-aging community are now doing to heal the body faster and to increase mitochondrial density. A sample 15 minute workout on this would be, for example, a five minute warmup at hypoxia, ten 30 seconds efforts of 15 seconds of hypoxic sprints followed by 15 seconds of hyperoxic sprints with 30 seconds of recovery, and a final 2 minute hyperoxic sprint. Similar the isometric training I told you about earlier, this allows me to get in and get out of my workout quickly, getting the equivalent of several hours of endurance training in one fell swoop that does, admittedly, take me into a brief journey to a pretty intense pain cave.

So thats it! Do you have questions, thoughts or feedback for me about this daily routine or the crazy stuff I get up to in the video that I may not have addressed above? Leave your comments below and I will reply!

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Shooting Up Stem Cells With Ben Greenfield The Down The ...

Stem Cell Doctor

Stem cells are the pinnacle of regenerative medicine. In comparison to prolotherapy and platelet-rich plasma therapy, stem cell therapy uses healthy adult stem cells harvested from the patients own tissues and takes advantage of the ability of these cells to replace injured or degenerated cells and promote regeneration.

Adult stem cells are harvested from bone marrow or adipose tissue. When injected into injured or degenerated tissue (tendons, ligaments, spinal discs, etc), stem cells release signaling molecules. If viable surrounding tissues are still present, these signaling molecules or growth factors stimulate repair and regeneration of these tissues in a natural way.

The most common condition we treat with stem cell therapy is low back pain from degenerative disc disease (discogenic lumbar pain). This is a chronic pain condition notorious for how hard it is treated through conventional treatments like epidural steroid injections or lumbar fusion surgery. Stem cell therapy offers a new and exciting alternative to this problem.

Other conditions treated with stem cell therapy are musculoskeletal injuries and degenerative conditions of the shoulder, knee, and hip.

At this time, stem cell therapy is considered an experimental treatment. Its success also hinges on establishing a correct diagnosis with our pain-mapping techniques, and on the chronicity and severity of the condition. When successful, stem cell therapy can replace older, invasive surgical procedures that are prone to complications and liable to create additional arthritic degeneration with time.

Stem cell injections are an office-based treatment. We collect bone marrow from the hip bone (iliac wing) or adipose tissue usually from the abdomen, harvest the stem cells through a minimal manipulation process like centrifugation, and concentrate them using our custom algorithms. The cells are then injected into the affected areas using precise live radiological guidance. The procedure may last anywhere from 1-3 hours, including mandatory rest and recovery time after our lumbar disc procedures. We offer office-based sedation when necessary and close follow-up after each procedure, tailored to the individual needs of each patient.

To find out more, and to learn if you are a candidate for autologous, point-of-care stem cell therapy, contact us for an appointment.

See more here:
Stem Cell Therapy Doctor | Westlake Austin Texas

Welcome to the Stem Cell Institute of Texas

The Stem Cell Institute of Texas provides the latest stem cell therapies using adult stem cells to treat a wide variety of health concerns. Our two main focuses cosmetics and orthopaedic conditions use adult stem cells to transform your appearance and function by stimulating the bodys repair mechanisms.

Cells derived from the Umbilical Cord of Live Healthy Birth Babies contains stem cells, growth factors, and proteins that stimulate YOUR body to regenerate damaged joints and tissue Just like in your youth!

Do you suffer from pain in your back or your joints, such as hip or knee, which prevents you from living life to the fullest? Is walking, cycling, gardening, fishing, or exercising, no longer possible with out pain? If you are missing out on your Golden Years, you need to see a regenerative medicine physician for a consultation. They can determine if the newest innovations in stem cell therapies are right for you.

The treatment is a simple non-surgical injection into the affected joint with no down time or lengthy recovery. You may maintain your normal lifestyle and allow the cells to create a balanced optimal environment in your joints so your body can repair itself. You should feel maximal results within 10 to 12 weeks at which time you can increase your activity levels to match your comfort, but understand that the regenerative process can continue for long periods of time.

Umbilical cord cells contain growth factors, proteins, and stem cells that continue to produce additional growth factors and proteins for a period of time. These components have the potential to positively affect the environment inside the joint and to stimulate your own tissue to aid in the regenerative process while ALSO stimulating your NATIVE STEM CELLS to aid in regeneration.

Go here to read the rest:
The Stem Cell Institute of Texas | San Antonio, TX

Why use microneedling with PRP?

A March 12, 2013 online article in the New York Daily News (http://www.nydailynews.com/life-style/health/kim-kardashian-vampire-facelift-bloody-mess-article-1.1285646. Accessed 15 Mar 2013.) highlighted the recent Vampire Facelift procedure undergone by celebrity socialite Kim Kardashian. Doctors facilitated the delivery of activated platelet-rich plasma (PRP) with the Dermapen micro needling device, which was portrayed as painful and bloodynot a pretty picture but apparently all the rage in Hollywood. Why on earth would anyone subject themselves?

Firstly, PRP is a powerful new technology that has the advantage of being derived from a patients own blood, quickly but carefully processed to concentrate the growth factors which stimulate the production of natural compounds that promote healthy, younger looking skin. The healthy glow is apparently astonishing andbecause its derived from the patientsafely obtained. Medical science has only begun to scratch the surface of whats possible with PRP.

Dermapen is the safest, least traumatic device among a class of medical devices known as micro needling devices which are growing in populatiry because theyre safe, affordable, effective, and easy to use. Dermal rollers are another example. Dermapen is ideal for PRP delivery for a number of reasons: 1) the sterile micro needling tips are disposable so theres no risk of cross contamination or need for pre-sterilization, 2) the device is easy to use and delivers wounds at a consistent depth, and 3) unlike dermal rollers the Dermapen wounds are pure punctures (not rolling tears) and thus less traumatic. Additionally, according to a recent issue of THE Aesthetic Guide [Nov/Dec 2012, pp. 3-9], the common technique of subdermal injection of PRP is not easily tolerated by patients in comparison. David Mozersky, M.D. (San Antonio, Tex.) chose Dermapen for his office precisely for that reason, as he stated in the article. Its hard to encourage the kind of multiple-treatment regimen necessary for long-term results, he said. Dermapen changed that for me.

So despite what appears to be a painful procedure for Ms. Kardashian, the Dermapen-assisted application of PRP is perhaps the ideal, explains Dr. Mozersky: Given the low cost, high patient tolerance, ease of use, safety and efficacy, Dermapen is a no-brainer. We dont often see this combination of simplicity and efficacy in this profession.

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Platelet-rich plasma, or PRP, is a term you may have heard of a lot lately. If not, then you will; PRP is growing in popularity among citizens and celebrities alike. PRP is the processing of harvested autologous blood into a concentration of growth factors and other beneficial compounds which are then re-introduced to stimulate the bodys natural regenerative mechanisms and restore or maintain a youthful appearance. Kim Kardashian herself recently underwent the touted Vampire Facelift on her reality TV show, and the footage was dramatic. That portion of her show was highlighted in a recent article in the online New York Daily News (http://www.nydailynews.com/life-style/health/kim-kardashian-vampire-facelift-bloody-mess-article-1.1285646. Accessed 15 Mar 2013.). The procedure looks bloody and painful, but doctors promise tremendous results for what is actually a fairly simple and safe procedure, and inexpensive in comparison to many aesthetic therapies.

Although it appeared quite painful on TV, the use of the Dermapen micro needling device to facilitate penetration of PRP is actually an ideal and tolerable method. In a recent issue of THE Aesthetic Guide David Mozersky, M.D., medical director of ContourLase Body Institute in San Antonio, Texas described why he uses Dermapen with his PRP procedures: By causing controlled micro-injuries with Dermapen, we can enhance the penetration of PRP without injection. While injection has been the common method of subdermal PRP delivery, it is much less tolerable than Dermapen-assisted PRP and was a hard sell. Its hard to encourage the kind of multiple-treatment regimen necessary for long-term results, he said. Dermapen changed that for me Given the low cost, high patient tolerance, ease of use, safety and efficacy, Dermapen is a no-brainer. We dont often see this combination of simplicity and efficacy in this profession.

David J. Mozersky, M.D.Founder & Director ContourLase Body InstituteThis treatment is suggested by Dr.Mozersky and is not and approved Indication of use by the FDA. Dermapen LLC cannot suggest treatments in the United States other than the Indications for Use regulated by the FDA for 21 CFR 878.4820. We reprint white papers as requested by our

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Kim Kardashian Micro Needling PRP with Stem Cells - Dermapen

Harvard scientist Jon Tilly proposed a radical new idea about how eggs are produced that called for the existence of ovarian stem cells which could continually produce new eggs. Stem cells are accepted as essential to sperm production in males. In men, the sperm stem cells (called spermatogonia) produce daughter cells that either make the final end product (new sperm cells) or make more stem cells in a continuing cycle of renewal.

Although accepted as dogma in the male system, the dogma regarding the ovary denied the existence of a renewable stem cell that could continually produce new eggs. The existing dogma was that every baby girl is born with all the eggs she will ever have and her eggs continually die off with age and are lost monthly after puberty. The ovarian stem cells was believed to only produce a defined number of eggs for a short time during fetal development but then became dormant for the rest of the females lifespan.

The problem with this dogma was that Tillys accounting of eggs lost in his experimental systems always ended up with more eggs than expected. The only way he could reconcile this discrepancy was to allow for the existence of a small population of ovarian stem cells which were capable of reactivating and contributing some eggs to the total. Most of his science colleagues were sure that he was wrong. It took him four years to prove the existence of these reactivated stem cells in the ovary by showing that stem cells he recovered from an aging ovary could be induced to make eggs again.

Tilly used cells from aged mouse ovaries, exposing them to the cellular environment of younger mouse ovaries and reactivating or rejuvenating the old stem cells which then started to produce eggs again. If the same could be done in humans, old ovaries could be reawakened to produce eggs. This would be a huge advance in the treatment of infertility since ovarian aging is considered irreversible. The only current treatment option for old ovaries which no longer produce eggs is to do IVF using eggs from a younger donor.

Unfortunately, it will likely be years, if not decades, before these scientific findings in a mouse model are converted to clinical treatments for patients. The typical path for moving a scientific discovery from bench to bedside treatment is excruciatingly slow because the clinical treatment must be proven to be both effective and safe. For reproductive treatments which produce children, the safety and health of those children is the primary concern.

First, treatments must be shown to be safe for both mother and offspring in other animal models, especially other primates like rhesus monkeys and chimpanzees. In vitro experiments with rare donated human ovarian tissue would also be necessary. If all the animal research and in vitro human tissue work still looks promising, clinical trials might start in humans, if institutional review boards give approval for the proposed research in humans. Because in vitro fertilization research is not funded by NIH, and stem cell funding is subject to erratic funded by NIH or individual states, this research will be slower to yield new clinical treatments compared to other non-controversial areas like cancer research.

Although anyone reading this today is unlikely to benefit personally from this research, it still opens a small door to the possibility of new treatments for advanced maternal age that dont involve giving up the genetic link between mother and child.

You can read more about Tillys research in this BioTechniques article Where do babies come from?.

Another scientist, Karim Nayernia, professor of stem cell biology at Newcastle Universitys Institute of Human Genetics, is researching the use of spermatogonial stem cells to revive fertility in the male, after chemotherapy or disease. In mouse studies, he was able to use stem cells from bone marrow and coax it to become sperm stem cells called spermatogonia. Transplants of these new stem cells into mice whose testicles were depleted of stem cells allowed the mice to father offspring. In 2009, his research team reported that they successfully produced human sperm-like cells from embryonic stem cells in vitro. There remain questions about the health of the mice offspring so this research is a long way from clinical use, but offers the possibility of new treatments for male infertility.

Another researcher, Richard Behringer, professor of genetics at the University of Texas MD Anderson Cancer Center has been using stem cells to understand what makes us male or female. His research may one day allow same sex couples to have genetic children together. First, he took stem cells from male mice, cultured them in such a way to cause the X and Y chromosomes to separate in culture, creating some daughter cells that were XO, a genetic type that creates a female genotype due to lack of a Y chromosome. Genetic material from these XO cells was used to replace the genetic material inside a mouse blastocyst. A surrogate mother mouse carried the XO blastocyst and gave birth to a female pup. The ovary of the pup produced eggs that contained DNA from the feminized male stem cell. This female offspring mated naturally with male mice to produce offspring from (essentially) two males.

Dr. Behringer is also investigating techniques to introduce a second X chromosome into an XO cell, creating a female egg cell from a male stem cell. There are decades of basic biology research to be done here which will provide insights into how sex differentiation works. These preliminary experiments are decades away from clinical use and may never be implemented if society as a whole remains uncomfortable with using science to circumvent male-female procreation.

Reproductive research has always been controversial. IVF was considered amoral and possibly dangerous in the beginning and yet is widely accepted today. Public opinion tends to come around if a new medical intervention is effective and causes no harm. If nothing else, stem cell research is unlocking the most basic secrets nature has and although we cant predict what new fertility treatments, if any, might arise, it is certainly worth understanding reproduction at the cellular and molecular level. Stem cells are proving extremely useful for reproductive research.

2011, Carole. All rights reserved.

Posted on January 12, 2011 at 2:03 pmhttp://fertilitylabinsider.com/2011/01/rejuvenating-gonads-with-stem-cells/http://fertilitylabinsider.com/2011/01/rejuvenating-gonads-with-stem-cells/trackback/Categorised under : Ethical Issues , Fertility Preservation , Inside the Lab , Repro Bio 101Tagged with : eggs from stem cells , reproductive research , sperm from stem cells , stem cell research

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Rejuvenating gonads with stem cells - Fertility Lab Insider

by Thomas P. Zwaka*

Gene therapy is a novel therapeutic branch of modern medicine. Its emergence is a direct consequence of the revolution heralded by the introduction of recombinant DNA methodology in the 1970s. Gene therapy is still highly experimental, but has the potential to become an important treatment regimen. In principle, it allows the transfer of genetic information into patient tissues and organs. Consequently, diseased genes can be eliminated or their normal functions rescued. Furthermore, the procedure allows the addition of new functions to cells, such as the production of immune system mediator proteins that help to combat cancer and other diseases.

Originally, monogenic inherited diseases (those caused by inherited single gene defects), such as cystic fibrosis, were considered primary targets for gene therapy. For instance, in pioneering studies on the correction of adenosine deaminase deficiency, a lymphocyte-associated severe combined immunodeficiency (SCID), was attempted.1 Although no modulation of immune function was observed, data from this study, together with other early clinical trials, demonstrated the potential feasibility of gene transfer approaches as effective therapeutic strategies. The first successful clinical trials using gene therapy to treat a monogenic disorder involved a different type of SCID, caused by mutation of an X chromosome-linked lymphocyte growth factor receptor.2

Figure 4.1. Indications Addressed by Gene Therapy Clinical Trials.

* Center for Cell and Gene Therapy & Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, Email: tpzwaka@bcm.tmc.edu

While the positive therapeutic outcome was celebrated as a breakthrough for gene therapy, a serious drawback subsequently became evident. By February 2005, three children out of seventeen who had been successfully treated for X-linked SCID developed leukemia because the vector inserted near an oncogene (a cancer-causing gene), inadvertently causing it to be inappropriately expressed in the genetically-engineered lymphocyte target cell.3 On a more positive note, a small number of patients with adenosine deaminase-deficient SCID have been successfully treated by gene therapy without any adverse side effects.4

A small number of more recent gene therapy clinical trials, however, are concerned with monogenic disorders. Out of the approximately 1000 recorded clinical trials (January 2005), fewer than 10% target these diseases (see Figure 4.1). The majority of current clinical trials (66% of all trials) focus on polygenic diseases, particularly cancer.

Gene therapy relies on similar principles as traditional pharmacologic therapy; specifically, regional specificity for the targeted tissue, specificity of the introduced gene function in relation to disease, and stability and controllability of expression of the introduced gene. To integrate all these aspects into a successful therapy is an exceedingly complex process that requires expertise from many disciplines, including molecular and cell biology, genetics and virology, in addition to bioprocess manufacturing capability and clinical laboratory infrastructure.

Gene therapy can be performed either by direct transfer of genes into the patient or by using living cells as vehicles to transport the genes of interest. Both modes have certain advantages and disadvantages.

Direct gene transfer is particularly attractive because of its relative simplicity. In this scenario, genes are delivered directly into a patient's tissues or bloodstream by packaging into liposomes (spherical vessels composed of the molecules that form the membranes of cells) or other biological microparticles. Alternately, the genes are packaged into genetically-engineered viruses, such as retroviruses or adenoviruses. Because of biosafety concerns, the viruses are typically altered so that they are not toxic or infectious (that is, they are replication incompetent). These basic tools of gene therapists have been extensively optimized over the past 10 years.

However, their biggest strengthsimplicityis simultaneously their biggest weakness. In many cases, direct gene transfer does not allow very sophisticated control over the therapeutic gene. This is because the transferred gene either randomly integrates into the patient's chromosomes or persists unintegrated for a relatively short period of time in the targeted tissue. Additionally, the targeted organ or tissue is not always easily accessible for direct application of the therapeutic gene.

On the other hand, therapeutic genes can be delivered using living cells. This procedure is relatively complex in comparison to direct gene transfer, and can be divided into three major steps. In the first step, cells from the patient or other sources are isolated and propagated in the laboratory. Second, the therapeutic gene is introduced into these cells, applying methods similar to those used in direct gene transfer. Finally, the genetically-modified cells are returned to the patient. The use of cells as gene transfer vehicles has certain advantages. In the laboratory dish (in vitro), cells can be manipulated much more precisely than in the body (in vivo). Some of the cell types that continue to divide under laboratory conditions may be expanded significantly before reintroduction into the patient. Moreover, some cell types are able to localize to particular regions of the human body, such as hematopoietic (blood-forming) stem cells, which return to the bone marrow. This quot;homingquot; phenomenon may be useful for applying the therapeutic gene with regional specificity.

A major disadvantage, however, is the additional biological complexity brought into systems by living cells. Isolation of a specific cell type requires not only extensive knowledge of biological markers, but also insight into the requirements for that cell type to stay alive in vitro and continue to divide. Unfortunately, specific biological markers are not known for many cell types, and the majority of normal human cells cannot be maintained for long periods of time in vitro without acquiring deleterious mutations.

Stem cells can be classified as embryonic or adult, depending on their tissue of origin. The role of adult stem cells is to sustain an established repertoire of mature cell types in essentially steady-state numbers over the lifetime of the organism. Although adult tissues with a high turnover rate, such as blood, skin, and intestinal epithelium, are maintained by tissue-specific stem cells, the stem cells themselves rarely divide. However, in certain situations, such as during tissue repair after injury or following transplantation, stem cell divisions may become more frequent. The prototypic example of adult stem cells, the hematopoietic stem cell, has already been demonstrated to be of utility in gene therapy.4,5 Although they are relatively rare in the human body, these cells can be readily isolated from bone marrow or after mobilization into peripheral blood. Specific surface markers allow the identification and enrichment of hematopoietic stem cells from a mixed population of bone marrow or peripheral blood cells.

After in vitro manipulation, these cells may be retransplanted into patients by injection into the bloodstream, where they travel automatically to the place in the bone marrow in which they are functionally active. Hematopoietic stem cells that have been explanted, in vitro manipulated, and retransplanted into the same patient (autologous transplantation) or a different patient (allogeneic transplantation) retain the ability to contribute to all mature blood cell types of the recipient for an extended period of time (when patients' cells are temporarily grown quot;outside the bodyquot; before being returned to them, the in vitro process is typically referred to as an quot;ex vivoquot; approach).

Another adult bone marrow-derived stem cell type with potential use as a vehicle for gene transfer is the mesenchymal stem cell, which has the ability to form cartilage, bone, adipose (fat) tissue, and marrow stroma (the bone marrow microenvironment).6 Recently, a related stem cell type, the multipotent adult progenitor cell, has been isolated from bone marrow that can differentiate into multiple lineages, including neurons, hepatocytes (liver cells), endothelial cells (such as the cells that form the lining of blood vessels), and other cell types.7 Other adult stem cells have been identified, such as those in the central nervous system and heart, but these are less well characterized and not as easily accessible.8

The traditional method to introduce a therapeutic gene into hematopoietic stem cells from bone marrow or peripheral blood involves the use of a vector derived from a certain class of virus, called a retrovirus. One type of retroviral vector was initially employed to show proof-of-principle that a foreign gene (in that instance the gene was not therapeutic, but was used as a molecular tag to genetically mark the cells) introduced into bone marrow cells may be stably maintained for several months.9 However, these particular retroviral vectors were only capable of transferring the therapeutic gene into actively dividing cells. Since most adult stem cells divide at a relatively slow rate, efficiency was rather low. Vectors derived from other types of retroviruses (lentiviruses) and adenoviruses have the potential to overcome this limitation, since they also target non-dividing cells.

The major drawback of these methods is that the therapeutic gene frequently integrates more or less randomly into the chromosomes of the target cell. In principle, this is dangerous, because the gene therapy vector can potentially modify the activity of neighboring genes (positively or negatively) in close proximity to the insertion site or even inactivate host genes by integrating into them. These phenomena are referred to as quot;insertional mutagenesis.quot; In extreme cases, such as in the X-linked SCID gene therapy trials, these mutations contribute to the malignant transformation of the targeted cells, ultimately resulting in cancer.

Another major limitation of using adult stem cells is that it is relatively difficult to maintain the stem cell state during ex vivo manipulations. Under current suboptimal conditions, adult stem cells tend to lose their stem cell properties and become more specialized, giving rise to mature cell types through a process termed quot;differentiation.quot; Recent advances in supportive culture conditions for mouse hematopoietic stem cells may ultimately facilitate more effective use of human hematopoietic stem cells in gene therapy applications.10,11

Embryonic stem cells are capable of unlimited self-renewal while maintaining the potential to differentiate into derivatives of all three germ layers. Even after months and years of growth in the laboratory, they retain the ability to form any cell type in the body. These properties reflect their origin from cells of the early embryo at a stage during which the cellular machinery is geared toward the rapid expansion and diversification of cell types.

Murine (mouse) embryonic stem cells were isolated over 20 years ago,12,13 and paved the way for the isolation of nonhuman primate, and finally human embryonic stem cells.14 Much of the anticipated potential surrounding human embryonic stem cells is an extrapolation from pioneering experiments in the mouse system. Experiments performed with human embryonic stem cells in the last couple of years indicate that these cells have the potential to make an important impact on medical science, at least in certain fields. In particular, this impact includes: a) differentiation of human embryonic stem cells into various cell types, such as neurons, cardiac, vascular, hematopoietic, pancreatic, hepatic, and placental cells, b) the derivation of new cell lines under alternative conditions, c) and the establishment of protocols that allow the genetic modification of these cells.

Following derivation, human embryonic stem cells are easily accessible for controlled and specific genetic manipulation. When this facility is combined with their rapid growth, remarkable stability, and ability to mature in vitro into multiple cell types of the body, human embryonic stem cells are attractive potential tools for gene therapy. Two possible scenarios whereby human embryonic stem cells may benefit the gene therapy field are discussed below.

First, human embryonic stem cells could be genetically manipulated to introduce the therapeutic gene. This gene may either be active or awaiting later activation, once the modified embryonic stem cell has differentiated into the desired cell type. Recently published reports establish the feasibility of such an approach.15 Skin cells from an immunodeficient mouse were used to generate cellular therapy that partially restored immune function in the mouse. In these experiments, embryonic stem cells were generated from an immunodeficient mouse by nuclear transfer technology. The nucleus of an egg cell was replaced with that from a skin cell of an adult mouse with the genetic immunodeficiency. The egg was developed to the blastula stage at which embryonic stem cells were derived. The genetic defect was corrected by a genetic modification strategy designated quot;gene targeting.quot; These quot;curedquot; embryonic stem cells were differentiated into hematopoietic quot;stemquot; cells and transplanted into immunodeficient mice. Interestingly, the immune function in these animals was partially restored. In principle, this approach may be employed for treating human patients with immunodeficiency or other diseases that may be corrected by cell transplantation.

However, significant advances must first be made. The levels of immune system reconstitution observed in the mice were quite modest (

Embryonic stem cells may additionally be indirectly beneficial for cellular gene therapy. Since these cells can be differentiated in vitro into many cell types, including presumably tissue-specific stem cells, they may provide a constant in vitro source of cellular material. Such quot;adultquot; stem cells derived from embryonic stem cells may thus be utilized to optimize protocols for propagation and genetic manipulation techniques.16 To acquire optimal cellular material from clinical samples in larger quantities for experimental and optimization purposes is usually rather difficult since access to these samples is limited.

The therapeutic gene needs to be introduced into the cell type used for therapy. Genes may be introduced into cells by transfection or transduction. Transfection utilizes chemical or physical methods to introduce new genes into cells. Usually, small molecules, such as liposomes, as well as other cationic-lipid based particles are employed to facilitate the entry of DNA encoding the gene of interest into the cells. Brief electric shocks are additionally used to facilitate DNA entry into living cells. All of these techniques have been applied to various stem cells, including human embryonic stem cells. However, the destiny of the introduced DNA is relatively poorly controlled using these procedures. In most cells, the DNA disappears after days or weeks, and in rare cases, integrates randomly into host chromosomal DNA. in vitro drug selection strategies allow the isolation and expansion of cells that are stably transfected, as long as they significantly express the newly introduced gene.

Transduction utilizes viral vectors for DNA transfer. Viruses, by nature, introduce DNA or RNA into cells very efficiently. Engineered viruses can be used to introduce almost any genetic information into cells. However, there are usually limitations in the size of the introduced gene. Additionally, some viruses (particularly retroviruses) only infect dividing cells effectively, whereas others (lentiviruses) do not require actively dividing cells. In most cases, the genetic information carried by the viral vector is stably integrated into the host cell genome (the total complement of chromosomes in the cell).

An important parameter that must be carefully monitored is the random integration into the host genome, since this process can induce mutations that lead to malignant transformation or serious gene dysfunction. However, several copies of the therapeutic gene may also be integrated into the genome, helping to bypass positional effects and gene silencing. Positional effects are caused by certain areas within the genome and directly influence the activity of the introduced gene. Gene silencing refers to the phenomenon whereby over time, most artificially introduced active genes are turned off by the host cell, a mechanism that is not currently well understood. In these cases, integration of several copies may help to achieve stable gene expression, since a subset of the introduced genes may integrate into favorable sites. In the past, gene silencing and positional effects were a particular problem in mouse hematopoietic stem cells.17 These problems led to the optimization of retroviral and lentiviral vector systems by the addition of genetic control elements (referred to as chromatin domain insulators and scaffold/matrix attachment regions) into the vectors, resulting in more robust expression in differentiating cell systems, including human embryonic stem cells.18

In some gene transfer systems, the foreign transgene does not integrate at a high rate and remains separate from the host genomic DNA, a status denoted quot;episomalquot;. Specific proteins stabilizing these episomal DNA molecules have been identified as well as viruses (adenovirus) that persist stably for some time in an episomal condition. Recently, episomal systems have been applied to embryonic stem cells.19

An elegant way to circumvent positional effects and gene silencing is to introduce the gene of interest specifically into a defined region of the genome by the gene targeting technique referred to previously.20 The gene targeting technique takes advantage of a cellular DNA repair process known as homologous recombination.21 Homologous recombination provides a precise mechanism for defined modifications of genomes in living cells, and has been used extensively with mouse embryonic stem cells to investigate gene function and create mouse models of human diseases. Recombinant DNA is altered in vitro, and the therapeutic gene is introduced into a copy of the genomic DNA that is targeted during this process. Next, recombinant DNA is introduced by transfection into the cell, where it recombines with the homologous part of the cell genome. This in turn results in the replacement of normal genomic DNA with recombinant DNA containing genetic modifications.

Homologous recombination is a very rare event in cells, and thus a powerful selection strategy is necessary to identify the cells in which it occurs. Usually, the introduced construct has an additional gene coding for antibiotic resistance (referred to as a selectable marker), allowing cells that have incorporated the recombinant DNA to be positively selected in culture. However, antibiotic resistance only reveals that the cells have taken up recombinant DNA and incorporated it somewhere in the genome. To select for cells in which homologous recombination has occurred, the end of the recombination construct often includes the thymidine kinase gene from the herpes simplex virus. Cells that randomly incorporate recombinant DNA usually retain the entire DNA construct, including the herpes virus thymidine kinase gene. In cells that display homologous recombination between the recombinant construct and cellular DNA, an exchange of homologous DNA sequences is involved, and the non-homologous thymidine kinase gene at the end of the construct is eliminated. Cells expressing the thymidine kinase gene are killed by the antiviral drug ganciclovir in a process known as negative selection. Therefore, those cells undergoing homologous recombination are unique in that they are resistant to both the antibiotic and ganciclovir, allowing effective selection with these drugs (see Figure 4.2).

Figure 4.2. Gene targeting by homologous recombination.

Gene targeting by homologous recombination has recently been applied to human embryonic stem cells.22 This is important for studying gene functions in vitro for lineage selection and marking. For therapeutic applications in transplantation medicine, the controlled modification of specific genes should be useful for purifying specific embryonic stem cell-derived, differentiated cell types from a mixed population, altering the antigenicity of embryonic stem cell derivatives, and adding defined markers that allow the identification of transplanted cells. Additionally, since the therapeutic gene can now be introduced into defined regions of the human genome, better controlled expression of the therapeutic gene should be possible. This also significantly reduces the risk of insertional mutagenesis.

Despite promising scientific results with genetically modified stem cells, some major problems remain to be overcome. The more specific and extensive the genetic modification, the longer the stem cells have to remain in vitro. Although human embryonic stem cells in the culture dish remain remarkably stable, the cells may accumulate genetic and epigenetic changes that might harm the patient (epigenetic changes regulate gene activity without altering the genetic blueprint of the cell). Indeed, sporadic chromosomal abnormalities in human embryonic stem cell culture have been reported, and these may occur more frequently when the cells are passaged as bulk populations. This observation reinforces the necessity to optimize culture conditions further, to explore new human embryonic stem cell lines, and to monitor the existing cell lines.23,24 Additionally undifferentiated embryonic stem cells have the potential to form a type of cancer called a teratocarcinoma. Safety precautions are therefore necessary, and currently, protocols are being developed to allow the complete depletion of any remaining undifferentiated embryonic stem cells.25 This may be achieved by rigorous purification of embryonic stem cell derivatives or introducing suicide genes that can be externally controlled.

Another issue is the patient's immune system response. Transgenic genes, as well as vectors introducing these genes (such as those derived from viruses), potentially trigger immune system responses. If stem cells are not autologous, they eventually cause immuno-rejection of the transplanted cell type. Strategies to circumvent these problems, such as the expression of immune system-modulating genes by stem cells, creation of chimeric, immunotolerable bone marrow or suppression of HLA genes have been suggested.25 In this context, nuclear transfer technology has been recently extended to human embryonic stem cells.26* Notably, immune-matched human embryonic stem cells have now been established from patients, including an individual with an immunodeficiency disease, congenital hypogammaglobulinemia.27* Strategies that combine gene targeting with embryonic stem cell-based therapy are thus potential novel therapeutic options.

Figure 4.3. Strategies for Delivering Therapeutic Transgenes into Patients.

2006 Terese Winslow

The addition of human embryonic stem cells to the experimental gene therapy arsenal offers great promise in overcoming many of the existing problems of cellular based gene therapy that have been encountered in clinic trials (see Figure 4.3). Further research is essential to determine the full potential of both adult and embryonic stem cells in this exciting new field.

* Editor's note: Both papers referenced in 26 and 27 were later retracted. See Science 20 January 2006: Vol. 311. no. 5759, p. 335.

Chapter 3|Table of Contents|Chapter 5

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Use of Genetically Modified Stem Cells in Experimental ...

WASHINGTON, D.C. Sgt. 1st Class Benjamin Heimstead, 25th Sustainment Brigade surgeon cell noncommissioned officer in charge, poses for a photo during his donation of bone marrow August 15 at the Georgetown University Medical Center. Only one in 430 people who have registered in the National Marrow Donor Program will go on to donate. (Photo by Capt. Aaron Moshier)

Staff Sgt. Heather Denby 25th Sustainment Brigade 25th Infantry Division

SCHOFIELD BARRACKS Sgt. 1st Class Benjamin Heimstead had only been in Hawaii for a few weeks before he received an email that would change the odds of survival for one special person.

My lab results showed that I was an excellent match, said Heimstead, the 25th Sustainment Brigade surgeon cell noncommissioned officer in charge. I had done a lot of research on bone marrow transplants, and it turns out that only 38 percent of those in need are able to find someone suitable to donate, so I knew this was something very special.

Heimstead participated in a bone marrow sample drive at Fort Bliss, Texas, in 2010 while he was stationed there. He went on to Fort Benning, Georgia, where he served as a drill sergeant for a couple years, and later as a senior operations NCO.

I really hadnt given the sample donation much thought after I did it, he said.

Seven years had passed before the match was found.

There are several steps toward ensuring a bone marrow match is made, according to the National Marrow Donor Program website. The steps are spread over several weeks and ensure an optimal match is made through medical evaluation.

Only 1 in 430 people who have registered in the NMDP will go on to donate; as of August, Heimstead is now one of them.

I thought I was ready for what was to come, he said. But nothing can prepare you for what the medicine is going to do to your body. The side effects were a lot of pain, insomnia and you cant take anything that is nonsteroidal or anti-inflammatory, because it will affect your platelets. But you know what? Id do it again in a heartbeat.

Heimsteads supervisor, Maj. Paula E. Young, 25th Sust. Bde. surgeon, said she will never forget the sacrifice her Soldier made.

I remember the disgruntled look on his face every time he would go to sit down or stand up from his desk, she said. The medicine that the donors are given build up their bone density, especially in your hips, and it can be quite painful.

Heimsteads final step in his bone marrow donation was coordinated through the C.W. Bill Young Department of Defense Marrow Donor Recruitment and Research Program, which flew him to Washington, D.C., where his stem cells were collected and prepared for transplant.

As a medic, Ive gotten used to being in the field, treating a patient and loading them up for transport, Heimstead said. Very rarely do you find out whether that patient survived, what happened or if you did the right thing on the spot, but this time I knew I had done the right thing.

This was one of those times where I could do what I had to do and actually have a really good chance of saving someones life, he continued.Heimstead will have to wait up to a year to find out if the transplant was successful through the MDRR program.

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Army medic donates bone marrow to stranger in need - Hawaii Army Weekly

In developing fetuses, infection by the Zika virus can result in devastating neurological damage, most notably microcephaly and other brain malformations. In a new study, published today in The Journal of Experimental Medicine, researchers at the University of California San Diego School of Medicine and Washington University School of Medicine in St. Louis report the virus specifically targets and kills brain cancer stem cells.

The findings suggest the lethal power of the virus notorious for causing infected babies to be born with under-sized, misshapen heads could be directed at malignant cells in adult brains. Doing so might potentially improve survival rates for patients diagnosed with glioblastomas, the most common and aggressive form of brain cancer, with a median survival rate of just over 14 months after diagnosis.

The Zika virus specifically targets neuroprogenitor cells in fetal and adult brains. Our research shows it also selectively targets and kills cancer stem cells, which tend to be resistant to standard treatments and a big reason why glioblastomas recur after surgery and result in shorter patient survival rates, said Jeremy Rich, MD, professor of medicine at UC San Diego School of Medicine. Rich is co-senior author of the study with Michael S. Diamond, MD, PhD, professor, and Milan G. Chheda, MD, assistant professor, both at Washington University School of Medicine in St. Louis.

Transmission electron microscope image of negative-stained, Fortaleza-strain Zika virus (red), isolated from a microcephaly case in Brazil. Image courtesy of NIAID.

This year, more than 12,000 Americans will be diagnosed with glioblastomas, according to the American Brain Tumor Association. Among them: U.S. Senator John McCain, who announced his diagnosis in July. They are highly malignant. The two-year survival rate is 30 percent.

Standard treatment is aggressive: surgery, followed by chemotherapy and radiation. Yet most tumors recur within six months, fueled by a small population of glioblastoma stem cells that resist and survive treatment, continuing to divide and produce new tumor cells to replace those killed by cancer drugs.

For Zhe Zhu, MD, PhD, a postdoctoral scholar in Richs lab and first author of the study, the hyper-reproductive capabilities of glioblastoma stem cells reminded him of neuroprogenitor cells, which fuel the explosive growth of developing brains. Zika virus specifically targets and kills neuroprogenitor cells.

So Zhu, with Rich, Diamond, Chheda and other collaborators, investigated whether the Zika virus might also target and kill cultured glioblastoma stem cells derived from patients being treated for the disease. They infected cultured tumors with one of two strains of the virus. Both strains spread through the tumors, infecting and killing stem cells while largely avoiding other tumor cells.

The findings, the authors said, suggest that chemotherapy-radiation treatment and a Zika infection appear to produce complementary results. Standard treatment kills most tumor cells but typically leaves stem cells intact. The Zika virus attacks stem cells but bypasses ordinary tumor cells.

We see Zika one day being used in combination with current therapies to eradicate the whole tumor, said Chheda, an assistant professor of medicine and of neurology at Washington University School of Medicine.

To find out whether the virus could boost treatment efficacy in a live animal, researchers injected either the Zika virus or a saltwater placebo directly into glioblastoma tumors in 18 and 15 mice, respectively. Two weeks after injection, tumors were significantly smaller in the Zika-treated mice, who survived significantly longer than those given the placebo.

The scientists note that the idea of injecting a virus notorious for causing brain damage into patients brains seems alarming, but they say Zika may prove a safe therapy with further testing because its primary target neuroprogenitor cells are rare in adult brains. The opposite is true of fetal brains, which is part of the reason why a Zika infection before birth produces widespread and severe brain damage while a normal Zika infection in adults typically causes mild symptoms or none at all.

The researchers also conducted studies of the virus using brain tissue from epilepsy patients that showed the virus does not infect non-cancerous brain cells.

As an additional safety feature, the research team introduced two mutations that weakened the viruss ability to combat natural cellular defenses against infection, reasoning that while the mutated virus would still be able to grow in tumor cells, which have a poor anti-viral defense system, it would be quickly eliminated in healthy cells with a robust anti-viral response.

When they tested the mutated viral strain and the original parental strain in glioblastoma stem cells, they found that the original strain was more potent, but that the mutant strain also succeeded in killing the cancerous cells.

Were going to introduce additional mutations to sensitize the virus even more to the innate immune response and prevent the infection from spreading, said Diamond, a professor of molecular microbiology, pathology and immunology. Once we add a couple more, I think its going to be impossible for the virus to overcome them and cause disease.

Co-authors of the study include: Matthew Gorman, Estefania Fernandez, Lisa McKenzie, Jiani Chai, Justin M. Richner, and Rong Zhang, Washington University, St. Louis; Christopher Hubert, and Briana Prager, Cleveland Clinic; Chao Shan, and Pei-Yong Shi, University of Texas Medical Branch; and Xiuxing Wang, UC San Diego.

Funding for this research came, in part, from the National Institutes of Health (R01 AI073755, R01 AI104972, CA197718, CA154130, CA169117, CA171652, NS087913, NS089272), the Pardee Foundation, the Concern Foundation, the Cancer Research Foundation and the McDonnell Center for Cellular and Molecular Neurobiology of Washington University.

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Zika Virus Targets and Kills Brain Cancer Stem Cells - UC San Diego Health

A new therapy changes the balance of osteoblasts (pictured here) and fat cells in the bone marrow, leading to stronger bones.

Science Picture Co/Science Source

By Emma YasinskiSep. 5, 2017 , 2:59 PM

A drug that can reverse diabetes and obesity in mice may have an unexpected benefit: strengthening bones. Experiments with a compound called TNP (2,4,6-trinitrophenol, which is also known as picric acid), which researchers often use to study obesity and diabetes, show that in mice the therapy can promote the formation of new bone. Thats in contrast to many diabetes drugs currently in wide use that leave patients bones weaker. If TNP has similar effects in humans, it may even be able to stimulate bone growth after fractures or prevent bone loss due to aging or disuse.

As more and more patients successfully manage diabetes with drugs that increase their insulin sensitivity, doctors and researchers have observed a serious problem: Thedrugs seem to decrease the activity of cells that produce bone, leaving patients prone to fractures and osteoporosis.

There are millions and millions of people that have osteoporosis [with or without diabetes], and it's not something we can cure, says Sean Morrison, a stem cell researcher at University of Texas Southwestern in Dallas. We need new agents that promote bone formation.

Morrison and his colleagues have shown that a high-fat diet causes mice to develop bones that contain more fat and less bone. The diet increased the levels of leptina hormone produced by fat cells that usually signals satiety in the brainin the bone marrow, which promoted the development of fat cells instead of bone cells. That suggests that nutrition has a direct effect on the balance of bone and fat in the bone marrow.

After reading Morrisons work, Siddaraju Boregowda, a stem cell researcher at the Scripps Research Institute in Jupiter, Florida, was reminded of genetically altered mice that dont gain body fat or develop diabetes, even when fed high-fat diets. He and his boss, stem cell researcher Donald Phinney, wondered whetherthose mice were also protected from the fattening of the bone marrow that accompanies a high-fat diet.

They contacted Anutosh Chakraborty, a molecular biologist who was studying such mice down the hall at Scripps at the time. The animals lack the gene for an enzyme called inositol hexakisphosphate kinase 1 (IP6K1), which is known to play a role in fat accumulation and insulin sensitivity. The scientists suspected that the lost enzyme might affect the animals' mesenchymal stem cells (MSCs)stem cells found in the bone marrow that are capable of developing into both thebone cells and fat cells that make up our skeletons. If too many fat cells develop, they take the place of bone cells, weakening the bone.

The researchers fed genetically altered and normal mice a high-fat diet for 8weeks. Not only did the genetically altered mice develop fewer fat cells than their normal counterparts, but their production of bone cells was higher than that of the normal mice, the team reported last month in Stem Cells.

The scientists then set out to see whetherthey could use a drug to achieve the same effect in normal mice. For 8weeks, they fed normal mice a high-fat diet and gave them daily injections of either TNP, a well-known IP6K1 inhibitor, or a placebo. When they analyzed the animals bones and marrow, they found that mice that had received TNP had significantly more bone cells, fewer fat cells, and greater overall bone area. The IP6K1 inhibitor apparently protected the mice from the detrimental effects of the high-fat diet.

The study provided thesurprising result that one new therapy currently being explored to lower insulin resistance promotes, rather than decreases, the formation of bone in mice, says DarwinProckop,a stem cell researcher at Texas A&M College of Medicine in Temple, who was not involved in the work.

The researchers still need to figure out how to deliver TNPs effects only to MSCs, instead of the entire body, given that it sometimes blocks other enzymes along with IP6K1. Inhibition of IP6K1 is a promising target for patients with both diabetes and obesity, Boregowda says. He says he and his colleagues are now enthusiastic about testing their findings in a wide range of bone-related diseases and disorders. It might even help heal broken bones, he speculates.

Phinney, on the other hand, is aiming even higher. He wonders whetherthe therapy could also be useful for space travel, because bones are especially vulnerable to deterioration in zero gravity. Its a whole new field of science and drug discovery.

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New therapy could protect diabetic bones - Science Magazine

Stem cells are essential building blocks for survival.A stem cellis responsible for acting as the foundation for every living being. They are capable of forming any tissue or organ in the body, which is unique from other cells. They can self-renew and replicate constantly. Their plasticity acts as another differentiator from other cells because their ability to create tissue for an organ different than their originating organ is essential to their benefit in regenerative medicine.

Stem celltreatments at the Lung Institute have continued to improve the functionality of lungs affected by chronic lung disease. The Lung Institute in Dallas, Texas, offers stem cell treatments with adult autologous stem cells. The cells come directly from an adult patients body only to be administered to the same patient. Using a patients own stem cells decreases the potential risk of rejection and undermines any possible controversy about stem cell therapy.

The Lung Institute in Texas provides twounique stem cell treatments: venous (blood-derived) and bone marrow. During a physician consultation, the recommended stem cell treatment will be determined based on patients health history and their current condition. Once the patient has the stem cell treatment, the stem cells target the damaged tissue or organ to promote healing, improve lung function and hopefully offer a better quality of life.

Receiving stem cell treatment at the Lung Institute in Dallas, Texas gives patients and their family members the opportunity to visit local historical, cultural and other tourist destinations. For example, on hot days, theMorton H. Meyerson Symphony Centeris a great way to beat the heat. Sit back, relax and let the Dallas Symphony Orchestra take you on a musical journey.

You can also find delicious local foods. To try some of the local Dallas flavors, check outFamous Smokey Johns Bar-B-Que, whichis known for its signature hickory smoked BBQ. If you are a seafood lover, Trulucks Seafood, Steak, and Crab Houseoffers a fresh seafood menu and great wine selection.

The Lung Institute in Texas is happy to answer your questions. With clinics nationwide, including in Dallas, Texas, we are here to help you. For more information about howstem cell treatment in Texascan be used to battlelung diseaseand improve your life or the life of a loved one,please feel free to contact usor call us at (800) 729-3065.

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Lung Institute | Stem Cell Treatment in Texas