Regenerative medicine and stem cells are often uttered within the same breath, for good reason.

In animal models, stem cells have reliably reversed brain damage from Parkinsons disease, repaired severed spinal cords, or restored damaged tissue from diabetes, stroke, blood cancers, heart disease, or aging-related tissue damage. With the discovery of induced pluripotent stem cells (iPSCs), in which skin and other tissue can be reversed into a stem cell-like state, the cells have further been adapted into bio-ink for 3D printing brand new organs.

Yet stem cells are hard to procure, manufacture, and grow. And unless theyre made from the patients own cell supplymassively upping production coststheyre at risk of immune rejection or turning cancerous inside their new hosts.

Thinking outside the stem cell box, two teams have now explored alternative paths towards repairing damaged tissue, both inside and outside the body. The first, published in Nature, found that a tiny genetic drug fully restored heart function in a pig after an experimental heart attack.

Pig hearts are remarkably similar to human hearts in size, structure, and physiology, to the point that they may eventually become candidates for pig-to-human xenotransplants. Although itll take some time before we can proceed to clinical trials, said lead author Dr. Mauro Giacca from Kings College London, the drugthe first of its kindis a promising move towards repairing heart damage directly inside patients.

The second study, outlined in Nature Communications, explores a radically different approach that restores damaged lungs, which can then be used for tissue transplantation. To address the pressing need for donor lungs, Dr. Matt Bachetta at Vanderbilt University and colleagues from Columbia University developed a new protocol that not only keeps donor pig lungs alive, but also repairs any damage sustained during the extraction process so that the organs meet every single criterion for transplantation.

Video Credit: Brandon Guenthart/Columbia Engineering

Both ideas are universal in that they can potentially be expanded to other organs. Unlike stem cell treatments, theyre also one size fits all in that the therapies will likely benefit most patients without individual tailoring.

To be clear, Giaccas new treatment isnt gene therapy, in that it doesnt fundamentally change a hearts genetic code.

Rather, it relies on weird little RNA fragments called microRNAs. Similar to RNA, which carries genetic code from DNA to our cells protein-making factories, these molecules are made up of four genetic letters and flow freely inside a cell.

Averaging just 22 letters, microRNAs powerfully control gene expression in that they can shut down a gene without changing its genetic code. Scientists dont yet fully understand how microRNAs work. But humans have up to 600 different types of these regulators floating around our cells, and theyve been linked to everything from cancer and kidney problems to brain development, transgenerational inheritanceand yesheart disease.

These mysterious genetic drugs could meet a critical clinical need. Although modern medicine has ways to reduce damage from heart attacks, surviving patients still often retain permanent damage to the hearts structure, Giacca explained. Unlike skin or liver cells, mature heart cells are stoic little buggers in that they dont usually replenish themselves. This causes the heart to lose its ability to properly contract and pump blood, which eventually leads to heart failure.

Giaccas team decided to see if they could kick mature heart cells back into dividing action, rather than forming scar tissue. Using a high-volume screen, they first looked through miRNAs that can stimulate mature heart cells to divide after a heart attack in mice. One promising candidate emerged: hsa-miRNA-199a-3p (yeah, catchy, I know).

Next, the team used a virus to deliver the microRNA candidate into the hearts of 25 pigs, which were subjected to an experimental heart attack that blocked blood flow to the heart for 90 minutes. The miRNA, restricted to only the heart, immediately worked its magic and shut down several genetic pathways. Although the heart still retained damage, measured two days following the heart attack, within a month it reduced scar tissue by 50 percent. The treated hearts were also far stronger in their ability to contract compared to non-treated hearts, and grew slightly in muscle size.

Under the microscope, the team found that the miRNA forced mature heart cells back into a younger state. The cells regained their ability to divide and supplement damaged tissue. Its not an easy surgery: the team directly jabbed the heart 20 times with the virus to ensure that the organ evenly received the genetic drug.

The therapy also comes with a potentially troubling consequence. The team followed 10 pigs after the one-month mark. Although their heart functions readily improved, seven suddenly died from heart tremors within three to four weeks without any warning. Subsequent detective work revealed that it could be due to overgrowth of new heart cells. The treatment needs careful dosing, they concluded.

Despite these hiccups, the miRNA therapy is a welcome new addition to the heart regeneration family. It is a very exciting moment for the field. After so many unsuccessful attempts at regenerating the heart using stem cells, which all have failed so far, for the first time we see real cardiac repair in a large animal, said Giacca.

Bacchettas lung recovery team took a different approach. Rather than trying to directly repair lungs inside the body, they tackled another clinical problem: the lack of transplantable donor lungs.

Roughly 80 percent of donor lungs are too damaged for transplantation, said Bacchetta. Although there are many sources of trauma, including injuries from ventilators or fluid buildup inside the organ, the team focused on a major cause of damage: stomach contents.

Lungs are sensitive snowflakes. Theyre extremely easily scuffed up by stuff that comes out of our stomachs, such as food particles, bile, gastric juices, and enzymes. If youve ever had a horrific hangover over the toiletwell, you know it burns. Usually our lungs can heal; but in the case of transplantationright after deaththey often dont have the time to self-repair.

This lung shortage led Bacchettas team to look for alternative ideas. We were searching for a way to extend the ability to provide life-saving therapy to patients, he said, a search that took seven years of banging their heads against a wall.

Then came the winning lightbulb moment: if man-made devices arent enough to repair lungs outside the body, what about the eventual recipient? After all, lungs dont work alonethey thrive in a physiological milieu chock full of molecules that activate when the body senses injury.

I decided, look, weve got to use the whole body. The only way to do that was to use the potential donor recipient essentially as a bioreactor, said Bacchetta.

The team first poured gastric acid into the lungs of an unconscious donor pig to mimic injury. After six hours, they extracted the damaged lung and placed it carefully into a warm, humidified sterile bowlthe organ chamberand hooked the organ up to a ventilator. They then connected the lungs blood vessels to the recipients circulation. This essentially uses the recipient to help break down toxic molecules in the injured lungs while supplying them with fresh nutrients and healing factors.

It sounds pretty gruesome, but the trick worked. When supplemented with a wash that rinsed out stomach juices, the lungs regenerated in just three days. Compared to non-treated lungs, their functions improved six-fold. The technique restored and maintained the function of donor lungs for up to 36 hours, but Bacchetta expects to further expand the window to days or even weeks.

Our work has established a new benchmark in organ recovery, said Bacchetta. It has opened up new pathways for translational applications and basic science exploration.

Neither study is perfect, but they represent new pathways into regenerative medicine outside stem cells. And when it comes to saving lives, its never good to put all eggs inside one (stem cell) basket, especially when the need is large, pressing, and unmet.

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New Progress in Stem-Cell-Free Regenerative Medicine

LOS ANGELES, CA / ACCESSWIRE / May 22, 2019 / In 2019's current health and beauty focused climate, people are on a quest to fight the signs of aging (or prevent it altogether) and many have begun looking for alternative ways to roll back the clock. With advancements in stem cell and platelet-rich plasma (PRP) therapy, more people are ditching standard procedures like facelifts for newer, regenerative treatments to reverse aging starting at the cellular level. Even athletes are seeing the effects of stem cell therapy to heal injuries and stimulate growth factors. But are these treatments really worth the cost? Are they effective enough to ditch your Botox? Board-certified plastic surgeon Dr. Sean Kelishadi discusses new cell-based treatments, traditional fillers and fat transfers to tell us which might be right for you.

How do stem cells work, what is stem cell therapy and how are people using it in the cosmetics field now?

First, we should distinguish the difference between adult and embryonic stem cells. Embryonic stem cells are derived from an embryo and can become all types of cells within the body. They don't have a specific function other than to be a manufacturing plant to create other types of cells. As we develop into a child these cells become more specific, called adult stem cells or multipotent stem cells. We have many of these cells as youth, but slowly, over time,

lose them as we age. Because of this, we take longer to recover from a sports injury or a wound as quickly. Several years ago, it seemed like there was no way to turn the clock back, until now. Recent research has discovered methods in which we can turn these cells back on or take them from one part of the body and place them in another. We are currently able to take blood and prepare it in a way to concentrate the platelets and white blood cells to turn these cells on for a while to reverse or slow aging or speed up the healing cascade. There are also methods of taking your fat, which was recently discovered as a storehouse for adult stem cells, like bone marrow, where we can transfer prepared fat to other parts of the body, like the face, to slow or reverse the aging of the skin and restore lost volume.

Is it possible to isolate the functionality of what you want those stem cells to do? For example, using them to repair sun damage, is it possible to isolate their functions for a specific purpose in the body?

The scientific evidence being published of late has shown we can take adult stem cells and cause them to form certain types of cells. For instance, adult stem cells from your fat can be grown into bone, cartilage, muscle and skin. This is all groundbreaking for the field of reconstructive surgery. For example, our cancer patients would get mastectomies and have their whole breast tissue removed and have implant reconstruction. They would just have a bag of skin over an implant, which would look unnatural as there's really no fat and all you could see were the ripples and the deformities from the implant. Some surgeons really thought ahead and decided to take some fat from the patient and put fat where these ripples were to lessen the appearance of the deformity. They also noticed that by doing this, the patients recovered faster from the procedure.

In contrast, there were some doctors and scientists that thought we shouldn't inject fat in the breasts of breast cancer patients because the stem cells in the fat could potentially enable breast cancer to develop again. It was kind of taboo to talk about this for a while. Fortunately, recent clinical studies have proven otherwise. What they also discovered is that with fat transfer on breast cancer patients with radiation damage, the damaged skin would also become soft and get better largely due to the stem cells found in fat. Just picture people who had radiated skin that looked like leather, and it healed. They realized there was a serious correlation between fat transfers and inadvertent repair and reproduction of healthy cells via innate stem cells in the fat. That's where a lot of my interest started in this research.

Are there different types of stem cells, if so, what are their functions?

Yes, we discussed earlier the difference between embryonic and adult stem cells. There are different subtypes that separate and expand on this. After embryonic, which are totipotent cells and can become a new organism, there are pluripotent, which can become all cell types and multipotent which can become many cell types of a particular family of cells; for example hemopoietic stem cells can become all types of blood cells. Most cell therapies we talk of are of this type, multipotent, and are considered adult stem cells. There are also cell types below the adult stem cell that have value with tissue and cell graft therapies like progenitor cells which function to support a specific tissue or cell type. As science is learning about the regenerative potential about these cells, we are noticing it's not the stem cell making new cells that have as much regenerative value but it's the signals that these stem or progenitor cells send which promote regeneration and repair as well.

Can you talk about how you're working with fat and injectables?

With the discovery 17 years ago by UCLA scientists, fat has been looked at differently ever since. There's a lot of different ways of harvesting and purifying fat before transfer. Traditionally, on average, only 30-50% of your fat grafts survived post-surgery to the face, breast or butt. What we've found in our research board is that there are many things to consider when pulling and transferring fat that leads to improved outcomes and what we call "graft-take". Some steps we did not consider in the past were that negative pressure intensity played a role as well as the size of the fat particles and the way you inject can significantly increase viability and results; basically, the gentler you handler the fat and less trauma you put it through the better will be its chances for survival after transfer. One of the exciting parts of my career is that I have helped work with a team that has developed processing and harvesting kits recently to make it where virtually anyone can inject fat successfully and you don't need any expensive equipment to do it. This kit is called the IntelliFat Injection Kit. We've been able to achieve over 95% viability with our methods.

When you take this fat and inject it, it works like a filler. I've got a new procedure I've started called Hips to Lips where we suck out fat from the hips and put it in your lips for example! You can also take fat and break it down into smaller particles and inject under the eye near the tear trough; that's a thinner skin so you need finer fat there.

Moreover, what we found is that if you break down the fat into even smaller particles, what you're left with is something called Stromal Vascular Tissue or "SVT". The SVT is the supporting infrastructure of the fat. It has all the stem and progenitor cells, growth factors and extracellular matrix, like collagen, required to create volume and get a regenerative aesthetic result. But, when you inject that, it doesn't work like a filler as the results can be longer lasting and provide a solid foundation in reversing facial atrophy. The added benefit is that is can often be more cost effective as well.

Some other cell therapies, though not a real stem cell therapy you may have heard of is the vampire facial, which uses PRP (Platelet Rich Plasma). How this works is some of your blood is put into a syringe, then it is centrifuged, or spun down. By that, they're able to concentrate the platelets and good white blood cells and remove the red cells which can cause bad types of inflammation, and when injected, can stimulate by the release of growth factors, local cells to grow and repair the local tissue. If you remember, back in the day when Amar'e Stoudemire or Kobe Bryant had issues with their knees, they were going to Germany and getting PRP injections to stimulate and speed repair.

This can also be done in the skin. As we age or get sun damage our skin gets thin due to many factors, but one is the diminishing of the capillaries. PRP may promote the development of new capillaries more since these platelet-derived growth factors have been shown to increase angiogenesis or the formation of new blood vessels. I often see people with very fair skin might see more pink skin tone if it turns on those signals. I like PRP for areas where patients need more blood flow like if you have a tear in your cartilage or something. But the S.V.T. we're talking about with the intelliFat is cool because now you can inject these stem and progenitor cells with the ability to release a broader and more powerful growth factor profile than that of PRP under the skin. By this, you can potentially create further repair or reversing of the loss of volume and skin tone.

Unfortunately, people are still going to age, Father Time is still undefeated - but this helps. Let's say you have somebody who's been having knee pain with arthritis, traditionally orthopedic surgeons were injecting cortisone in those areas because it's an anti-inflammatory, and that's great, but it weakens the tissue over time so you can't get those injections all the time. But what if you inject these stem cells there and it helps to heal arthritis? That might not be a cure but what if it makes the knee well enough to not bother you when you walk?

Is the board that you're focused on taking a responsible approach to studying the mechanisms that you are using?

Yes. What we're doing with the Intelligent Fat Advisory Board is kind of like building a bridge between aesthetic medicine and regenerative medicine. I'm proud to be part of the Intelligent Injectable Advisory Board because a lot of smart people from different disciplines are there and we're able to move these kinds of technologies forward with great thinking, science and studies. There are people who get excited about this and think, great we can isolate or grow adult stem cells from fat or bone marrow; why don't we just inject in an organ, eye, or the vein and put it through the whole body, and that's where it gets dangerous. Some clinics you might have heard of have had deaths or serious complications because you shouldn't be injecting your stem cells in this manner unless as part of a clinical study or without another safer option. There are certain limitations that you can't do with this stuff. You can't just infuse your body with stem cells intravenously and hope everything heals. It's more about how you apply this stuff. Some of these potential cell therapies are very powerful but we need the right people delivering the right type of cells doing these procedures.

In your opinion, who is the best candidate for fat transfer versus the best candidate for stem cell procedures?

We'll talk about fat transfers first. Let's say you have a woman who's gone through pregnancy and the hormones made them gain weight and they've worked out and dieted all they can after having the baby. They look great, they still have their tissue but they just can't get rid of their muffin top, so they have this lump of fat right over the love handles. That sometimes just becomes hormone resistant fat just because of what happens in their pregnancy. For those people, you can do liposuction and then you can take that fat and put it where they feel kind of saggy like in their buttocks or some other area. Basically, you could take that fat and inject it and use it as a filler. So that's a great candidate for fat transfer. Also, somebody who has aged, and they've lost volume in their face, but they have a little bit of fat that you can suck out and use for their face. Or for example, you have somebody who loves to get their lips filled with fillers, but they just don't want to come in every three to six months and they want them to last 3 or 4 years longer -- then I would put fat in their lips.

As a plastic surgeon when you do these procedures does it seem that fat transfers appear more natural than fillers for the face? Or is there any difference at all in appearance?

Part of the facial rejuvenation process is restoring volume, lifting the tissues underneath, getting rid of excess skin, and tightening things. I also have to put fat back where it belongs or is needed. I love doing fat grafts in my facelift patients and I think it's a great filler, but also what I've noticed is, when those stem cells kick in, their skin looks rejuvenated and the overall quality and texture feels better. Magical things happen that I'm not even controlling!

When it comes to fillers, I think they're amazing. I love fillers and a lot of the fillers now are made of Hyaluronic Acid which is still a natural product. This is a naturally occurring substance in the body and is what lubricates your joints, so when you inject it, it draws in water. The reason why some people look bad with filler is that they might have too much, but more importantly, I think they're being injected in the wrong places. If you're putting in filler trying to restore volume that's been lost and you don't know the anatomy, it looks bad. A lot of people get their nasolabial folds filled but the reality is they look deeper because their cheek has fallen. So if you don't fill the cheek and you just keep injecting a nasolabial fold, the patient is going to look like a monkey, the bottom line you have to know your anatomy.

Also if you're going to use filler, you have to figure out the thickness of the filler depending on the location, because the eyelid is different than the jawbone. So you've got to choose a filler that corresponds to the thickness you need. Fat is the same way; you could just take the fat that you suck out and inject it, but in areas near the eyelid you've got to break it down into smaller particles so it's not so easily seen under the skin. Please note that fat's great, but my only hesitation with fat transfer is that if you take fat, you want to do it in someone who is weight-stable. If it's somebody who yo-yo diets and just lost a bunch of weight and you suck out fat and you put it in their face when they gain weight that fat will still gain weight. That's an instance where people can look really bad with a fat transfer to the face if their diet is not stable. You don't want to do that with someone who has unstable weight because whatever fat you suck out and put in a new location will behave like where it came from. So when you lose weight you get smaller and when you gain weight you get bigger. The nice thing with fat though is if they're weight stable and they've had fillers before and they know the look they want, for example, they want their lips big or they want their cheeks to look fuller, you can make that happen with fat. I wouldn't inject somebody who's never had their lips filled with a bunch of fat if I don't know what look they really like. They can tell me they like something but I'm going to try it out with fillers first because fillers you can reverse if needed.

What about the regenerative component of this new technology? When do we try to regenerate cells versus using a filler?

When you get to the regenerative medicine component of it you can have people who have pain due to arthritis or inflammation, or a torn structure that's not healing because it needs better blood flow (some people just need surgery and that's fine), you can inject stem cells to help. So in that sense, you're not going to need a filler, for example, to make someone's knee cap sexier but you're going to put stem cells there from fat to utilize those factors that are going to help them heal. So that's where you kind of make the differentiation. I like to use fillers for the face where people are deflated, but let's say someone just has horrible pigment changes, acne, red spots, hyperpigmentation. I can inject the stem cells isolated from fat and I don't need to use the whole fat particles because I'm not trying to make their face bigger, I just want the growth factor to turn on the magic. So to do that, you must first break the fat into smaller particles and isolate the SVT.

The stem cells are like little keys.

Exactly! It's a very exciting time in medicine and I'm lucky to be talking with several companies that are looking at stem cells, PRP, growth factors and also what we can do with fat. I'm in the middle of some big discussions with a couple of big companies that are leaders in regenerative medicine.

Do you think we will eventually start to move into genetically modified cosmetics to prevent the need for surgery with the advent of therapies like PRP and stem cell?

Well, I think we're trying to connect the dots with all this technology we have in the world of tissue engineering. We're trying to do things like make a kidney out of your own cells and give it back to you. Because if you think about it, with all of the people who are on dialysis -there are not enough kidneys available for them. We don't have donors, so we're trying to make kidneys out of tissue engineering scaffolds. That's really high-end stuff, to be able to make a heart for a baby that needs a heart and can't get a transplant. I think this is really cool! For my own patients I've got really skinny, fit, fitness models that come to me and they tell me, "I want a bigger butt" and I can make the best of it with breast implants to make their breasts larger and more attractive, but they don't want butt implants because they're hard to maintain (and they don't look as natural) but they don't have any fat for me to suck out. I want to see the day where we suck out somebody's fat and then we can grow their fat in a petri dish with their own genetics, and then we can put all the fat they want in their own butt. When somebody gets a bigger burn and they don't have enough skin to get skin grafting from, they take pieces of skin and they send it to a lab and they're able to grow skin. Why shouldn't we do the same with other tissue?

For long term benefits do you think it might be better in the future for people to go with fat transfers over implants if they can? For health purposes do you recommend one over the other?

I'm a big implant fan and I know there's been a lot of stuff in the news about implants and so forth but a lot of it's anecdotal. We're aware that there are people that have complaints out there but I think implants are very safe. Ever since 2006, the silicone implants were brought back on the market by the FDA. We do over 350,000 new breast augmentation cases a year in the U.S. That's a lot! That's over 5 million people who got breast implants (when you consider revisions, exchanges, and new implants) in the last 10 years. I think if safety was really an issue we'd know more about it. We'd be hearing about it a lot more than we sometimes hear about. So I think breast implants are very safe. I don't have any safety concerns about them if they're done right. The other thing is, from a safety standpoint, I can do breast augmentation in one hour. And I think they help provide shape and structure to the breast. People have often lost weight or they've got some deflation from pregnancy and breastfeeding or they're just born with small breasts and you need something sturdy that can push that tissue up. I've got women for example who have big breasts and I do a breast reduction and they don't like the way their breasts look because they feel kind of soft and saggy to them and they want an implant so they can get that cleavage.

I think fat's great but I don't think it does what implants do. And the other thing is I can do that breast augmentation in under an hour of surgery whereas fat transfers you've got to suck out fat, you've got to purify the fat and then you've got to inject the fact. That surgery takes longer and it's pretty hard to beat the shape of an implant. We have so many different implant sizes, shapes and profiles. We could make anybody look however they want but with fat you're limited because there are only so many places you can inject and you don't just get to pick what it's going to look like.

Is there one that is more cost-effective than the other?

I think breast augmentation is much more cost effective because you're paying for much less operating room time and anaesthesia fees. People worry about the 10-year rule with implants, but implants nowadays are so sturdy. They're almost built to last a lifetime and they all come with a lifetime warranty. For example one of the companies I work with called Sientra is based out of Santa Barbara and their implants come with a lifetime warranty, so if they rupture let's say between now and the rest of your life, they replace your implants for free. That's a two thousand dollar value! They also have something where they say if your implants rupture within 20 years after your surgery they'll also give you $5,000 for surgery. That's pretty amazing. If they thought their implants were going to break down, they'd never give a warranty like that. I think bang-for-the-buck, implants are better because they give you shape that you can customize, they provide structure and they allow less surgical time. I think it's the way to go.

I recommend fat more for somebody who is skinny and you can see their underlying skeleton. I'll have somebody come to me and their rib sticks out more on one side than the other and even when you put a breast implant in you can see that rib that sticks out more on one side because they're so boney. For someone like that we can fat graft over the bone and make it look like the other side that doesn't stick out. So in essence, I like to use fat grafting to complement the work we do with implants, like icing on a cake.

If you need to fluff your lips is fat the right way to go?

It's a great way to go. But again I'm going to first start with a filler just so I can figure out exactly what look they want and then, later on, I can inject it with fat to make it exactly what they want. With respect to the breasts, I think of fat as icing on a cake. I think it's great but the reality is that you still need the cake. The implants are the cake, the fat's the icing if you need it.

What procedures are you offering right now in terms of fat transfer and stem cell therapy?

We're still doing Brazilian Butt Lifts (liposuction with fat transferred to the buttocks and hips) also doing facelifts and neck lifts. I am using fat for my facial rejuvenation but for in-office procedures, I am offering micro-needling and using some of their fat, processing it and bringing out the stem cells, growth factors and what we call the Stromal Vascular Tissues or "SVT" and putting that through the channels that are drilled. I think I'm going to be working in collaboration with some other specialities where we will isolate this fat and inject it as stem cells for arthritic joints or areas that are not healing for my patients with sports injuries that don't need surgery. They have to be a non-surgical candidate. And I do a lot of filler if somebody wants that. It's totally cool.

Visit Dr. Kelishadi at http://www.sskplasticsurgery.com

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How Stem Cell Therapy Is Transforming Cosmetic Surgery

By Chelsea Toledo, NIH/NIGMS | July 18, 2012 08:06pm ET

Credit: NIH

But scientists supported by the National Institutes of Health are learning more and more about the basic biology of stem cells. They are pinpointing the unique properties and potential of each type: embryonic stem cells that can become just about any cell, adult stem cells that can become specialized tissue or organ cells, and induced pluripotent stem cells that are mature adult cells reprogrammed to act like embryonic ones.

Here are five findings that illustrate the substantial strides researchers have made in understanding all the stem cell characters and their future fates.

Credit: From The Romance of King Arthur and His Knights of the Round Table illustrated by Alfred Pollard, 1917.

Up until a few years ago, scientists thought that genes specific to types of tissue were dormant until stem cells differentiated into heart, bone, skin or other kinds of cells. But then researchers at the University of California, Los Angeles, discovered that proteins mark these genes early on, during the pluripotent stage when cells have the potential for a wide range of future functions. The scientists now think that stem cells ability to differentiate into their different destinies may depend on the presence of these marks. The insight could help researchers better understand the nature of pluripotency and make sure that stem cells are fully functioning and competent to fulfill the desired destiny before being tested as treatments.

Credit: From The Three Little Pigs by L. Leslie Brooke, 1904.

Not all stem cells start out the same: Like the houses of the Three Little Pigs, some seem to be built from straw and others from bricks. Scientists at Brown University determined that the physical properties of stem cells can predict the type of tissue for which the cells are most suited. They found that bone cells were best developed from stiff stem cells; that fat could most easily form from soft, squishy stem cells; and that cartilage cells could best be created from stem cells with a high viscosityor resistance to tensile stress. For the distant future, the researchers envision stem cell retrieval, sorting and therapy occurring in the same procedure; surgeons repairing a bone could, for example, extract excess fat from the patient and choose the stiffest stem cells to inject at the surgical site.

Credit: From Cinderella; or, the little glass slipper, edited by Andrew Lang, 1889.

When Cinderellas fairy godmother made a pumpkin into a carriage, she had to use the right spell. Similarly, to coax stem cells to form only the type of cells that they want, scientists have learned that it takes the right formula. Researchers at the McEwen Centre for Regenerative Medicine in Toronto, Canada, created a concoction of nutrients and proteins that spurred human embryonic stem cells to become heart progenitor cells, or adult heart cells in their beginning stages. Those cells then grew into the three different types that make up functioning heart muscle. This work advances our understanding of how the heart develops and brings scientists one step closer to being able to create heart tissue for therapeutic purposes. It also provides an opportunity for researchers to test treatments on functioning heart cells in a lab dish.

Credit: From From Mjallhvt (Snow White), 1852.

Sometimes the best thing a stem cell can become is nothing at all. If their DNA is harmed at a critical stage by exposure to chemicals, radiation, viruses or other factors, embryonic stem cells quickly kill themselves to prevent the damage from spreading as the cells divide. Researchers from the University of North Carolina at Chapel Hill have just described how. Unlike their adult counterparts, human embryonic stem cells have an active version of the protein Bax, which can shut the cells down by communicating with other key proteins. To prevent accidental cell suicide, each stem cell stores its poison apple in the Golgi apparatus, where it is less likely to interact with those proteins. This new understanding could aid the development of stem cell therapies, perhaps to replace cells lost in conditions like Parkinsons disease.

Credit: Swan princess by Mikhail Vrubel, 1900.

Learn more:

Mastering Stem Cells: Profile of a Stem Cell Biologist

All-in-One Stem Cells from Inside the Cell

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Inside Life Science: Once Upon a Stem Cell

Your body has many different types of cells (more than 200 to be more exact) each geared toward specific functions. You have skin cells and blood cells, and you have bone cells and brain cells. All your organs comprise specific cells, too, from kidney cells to heart cells.

Your cells didnt start out knowing how to come together to form your bones, heart or blood; they begun with more of a blank slate. These completely undifferentiated cells can be found during gestation, or the time the baby is in the womb, and are called embryonic stem cells. These early stage stem cells are master cells that have the potential to become any type of cell in the body.

First isolated in 1998, there is a lot of controversy around acquiring embryonic stem cells. Thankfully, we can also acquire stem cells that form just a little bit later down the road, like in the umbillical cord. These stem cells, known as adult stem cells, stay with us for life. (Later, we will learn why not all adult stem cells are equal.) Adult stem cells are more limited in the types of cells they can become, something known as being tissue-specific, but share many of the same qualities. Hematopoietic stem cells (Greek to make blood and pronounced he-mah-toe-po-ee-tic) found in the umbilical cord's blood, for instance, can become any of the different types of blood cells found in the body and are the foundation of our immune systems. Another example is mesenchymal (meh-sen-ki-mal) stem cells, which can be found in the umbilical cord tissue and can become a host of cells including those found in your nervous system, sensory organs, circulatory tissues, skin, bone, cartilage, and more.

To recap, we have certain types of stem cells that can become a variety of different cellsthey are like the renaissance men of cellsbut there is one more thing that makes stem cells special. This has to do with how they replicate themselves.

The body has two ways to create more cells. The first is usually taught in middle school science. Known as cell division, its where a cell replicates within its membrane before dividing into two identical cells. Cells do this as needed for regeneration, which we will touch on in a second.

The other way the body creates more cells is through its stem cells, and stem cells do things a little differently. They undergo what is called asymmetric division, forming not one but two daughter cells: one cell often an exact replica of itself, a new stem cell with a relatively clean slate, and another stem cell that is ready to turn into a specific type of cell. This trait is known as self-renewal and allows stem cells to proliferate, or reproduce rapidly.

Through these two means, we are always producing more cells. In fact, much of your body is in a state of constant renewal because many cells can live for only certain period of time. The lifespan for a cell in the stomach lining is about two days. Red blood cells, about four months. Nerve and brain cells are supposed to live forever. This is why these cells rarely regenerate and take a long time if they do.

Different cells have different life cycles, and many are constantly regenerating, but when damage occurs and the body needs to come up with a new supply of cells to heal itself, it relies on the stem cells ability to quickly create more cells to repair the wound. Herein lays the potential for the introduction of new stem cells to enhance or be the driving factor in the healing process.

Scientists first found ways to use stem cells in bone marrow, and following this discovery, the first stem cell transplant was performed in 1956 via bone marrow between identical twins. It resulted in the complete remission of the one twins leukemia.

This and all other stem cell therapies since involve introducing new stem cells into the area to encourage the healing process. Often, the stem cell will create a particular type of cell simply because it is in proximity to other cells of that type. Unfortunately, researchers still had a ways to go before they could use stem cells from unrelated persons.

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Stem Cells Explained | What are Stem Cells?

The moral status of the embryo is a controversial and complex issue. The main viewpoints are outlined below.

1. The embryo has full moral status from fertilization onwardsEither the embryo is viewed as a person whilst it is still an embryo, or it is seen as a potential person. The criteria for personhood are notoriously unclear; different people define what makes a person in different ways.

Development from a fertilized egg into to baby is a continuous process and any attempt to pinpoint when personhood begins is arbitrary. A human embryo is a human being in the embryonic stage, just as an infant is a human being in the infant stage. Although an embryo does not currently have the characteristics of a person, it will become a person and should be given the respect and dignity of a person.

An early embryo that has not yet been implanted into the uterus does not have the psychological, emotional or physical properties that we associate with being a person. It therefore does not have any interests to be protected and we can use it for the benefit of patients (who ARE persons).

The embryo cannot develop into a child without being transferred to a womans uterus. It needs external help to develop. Even then, the probability that embryos used for in vitro fertilization will develop into full-term successful births is low. Something that could potentially become a person should not be treated as if it actually were a person. A candidate for president is a potential president, but he or she does not have the rights of a president and should not be treated as a president.

2. There is a cut-off point at 14 days after fertilizationSome people argue that a human embryo deserves special protection from around day 14 after fertilization because:

3. The embryo has increasing status as it developsAn embryo deserves some protection from the moment the sperm fertilizes the egg, and its moral status increases as it becomes more human-like.

There are several stages of development that could be given increasing moral status:

1. Implantation of the embryo into the uterus wall around six days after fertilization.2. Appearance of the primitive streak the beginnings of the nervous system at around 14 days.3. The phase when the baby could survive if born prematurely.4. Birth.

If a life is lost, we tend to feel differently about it depending on the stage of the lost life. A fertilized egg before implantation in the uterus could be granted a lesser degree of respect than a human fetus or a born baby.

More than half of all fertilized eggs are lost due to natural causes. If the natural process involves such loss, then using some embryos in stem cell research should not worry us either.

We protect a persons life and interests not because they are valuable from the point of view of the universe, but because they are important to the person concerned. Whatever moral status the human embryo has for us, the life that it lives has a value to the embryo itself.

If we judge the moral status of the embryo from its age, then we are making arbitrary decisions about who is human. For example, even if we say formation of the nervous system marks the start of personhood, we still would not say a patient who has lost nerve cells in a stroke has become less human. (But there is a difference between losing some nerve cells and losing the complete nervous system - or never having had a nervous system).

If we are not sure whether a fertilized egg should be considered a human being, then we should not destroy it. A hunter does not shoot if he is not sure whether his target is a deer or a man.

4. The embryo has no moral status at allAn embryo is organic material with a status no different from other body parts.

Fertilized human eggs are just parts of other peoples bodies until they have developed enough to survive independently. The only respect due to blastocysts is the respect that should be shown to other peoples property. If we destroy a blastocyst before implantation into the uterus we do not harm it because it has no beliefs, desires, expectations, aims or purposes to be harmed.

By taking embryonic stem cells out of an early embryo, we prevent the embryo from developing in its normal way. This means it is prevented from becoming what it was programmed to become a human being.

Excerpt from:
Embryonic Stem Cell Research: An Ethical Dilemma

A stem cell transplant is a procedure that replaces defective or damaged cells in patients whose normal blood cells have been affected by cancer.Stem cell transplants commonly are used to treat leukemia and lymphoma, cancers that affect the blood and lymphatic system. They also can help patients recover from or better tolerate cancer treatment.

In addition, these stem cell transplants are used to treat hereditary blood disorders, such as sickle cell anemia, and autoimmune diseases, such as multiple sclerosis.

Stem cell transplants use hematopoieticstem cells. These immature cells begin life in the bone marrow and eventually develop into the various types of mature blood cells, including:

There are two types of stem cell transplantation:

Cells are harvested from the patient's own bone marrow before chemotherapy and are replaced after cancer treatment. These are used most often to treat diseases like lymphoma and myeloma. They have little to no risk of rejection or graft versus host disease (GVHD) and are therefore safer than allogeneictransplants.

Stem cells come from a donor whose tissue most closely matches the patient.These cells can also come from umbilical cord blood extracted from the placenta after birth and saved in special cord blood banks for future use. MDAnderson's Cord Blood Bank actively seeks donations of umbilical cords.

Allogeneic transplants are often used to treat diseases that involve bone marrow, such as leukemia. Unlike autologous transplants, they generate a new immune system response to fight cancer. Their downside is an increased risk of rejection or GVHD.

Stem cell transplant patients are matched with eligible donors by human leukocyte antigen (HLA) typing. HLA are proteins that exist on the surface of most cells in the body. HLA markers help the body distinguish normal cells from foreign cells, such as cancer cells.

HLA typing is done with a patient blood sample, which is then compared with samples from a family member or a donor registry. It can sometimes take several weeks or longer to find a suitable donor.

The closest possible match between the HLA markers of the donor and the patient reduces the risk of the body rejecting the new stem cells (graft versus host disease).

The best match is usually a first degree relative (children, siblings or parents). These can be full matches or half-match related transplants, also known as haploidentical transplants.However, about 75% of patients do not have a suitable donor in their family and require cells from matched unrelated donors (MUD), who are located through registries such as the National Marrow Donor Program.

Because the patients immune system is wiped out before a stem cell transplant, it takes about six months to a year for the immune system to recover and start producing healthy new blood cells. Transplant patients are at increased risk for infections during this time, and must take precautions. Other side effects include:

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Stem Cell Transplants | MD Anderson Cancer Center