Category Archives: Stem Cells

SAN DIEGO, CA--(Marketwire - Mar 22, 2013) - Medistem Inc. ( PINKSHEETS : MEDS ) announced today it published an update on its RECOVER-ERC congestive heart failure Phase II clinical trial in a peer-reviewed journal (link to paper http://www.translational-medicine.com/content/pdf/1479-5876-11-56.pdf). The publication reports safety of its proprietary stem cell population, termed "Endometrial Regenerative Cells" (ERC), as well as data supporting the patent-pending 30 minute catheter-based retrograde delivery technique through which the stem cells are administered.

"To date, all stem cell trials in the cardiac space use bone marrow and adipose tissue sources.Unlike the painful and highly invasive process of collecting bone marrow and adipose stem cells, our collection processes involves extraction of a small amount of menstrual blood from young healthy donors.In our FDA-cleared manufacturing protocol, one donor generates 20,000 doses," said Alan Lewis, Ph.D., Chief Executive Officer of Medistem. "ERC are administered without tissue matching or the requirement for immune suppressive drugs. Our product is delivered to the point-of-care as a cryogenically preserved allogeneic therapy that is ready to use, without need for end user manipulation.This feature could make it practical for clinicians to efficiently deliver stem cell therapy to large numbers of heart failure patients."

"This is the first time that the minimally-invasive catheter-based retrograde delivery technique has been used in the context of a 'universal donor' stem cell," said Amit N. Patel, M.D., Director of Cardiovascular Regenerative Medicine at the University of Utah and the senior author of this publication."The delivery technique used in the current study can be widely performed by any licensed interventional cardiologist with minimal training.This is in contrast to other stem cell delivery techniques that require extensive user training and complex equipment that is not readily available."

The RECOVER-ERC trial is a 60 patient, double-blind, placebo controlled study in which patients with congestive heart failure are divided into 3 groups, which receive ERC in a dose escalating manner of 50, 100,and 200 million cells.Main efficacy endpoints are at 6 months after treatment with safety endpoints assessed up to one year.

To date, 17 patients have been treated with no treatment associated adverse events reported.The Principle Investigator is Leo Bockeria, M.D., Chairman of the Bakoulev Center and Academician of the Russian Academy of Science.The Bakoulev Center is Russia's premier institute for cardiovascular surgery and cardiology. Every year the Backulev Center performs approximately 30,000 procedures including 7,000 open heart surgeries and more than 12,000 angioplasties.

Amit Patel, M.D., is the International Principle Investigator for the trial and was the first physician to administer stem cells into the human heart.

Safety oversight for the trial is performed by the independent Data Safety Monitoring Board (DSMB) which is chaired by Warren Sherman, M.D., Director of Cardiac Cell-Based Endovascular Therapies at Columbia University.

About Medistem

Medistem Inc., is focused on the development of the Endometrial Regenerative Cell (ERC), a universal donor adult stem cell product. ERCs possess specialized abilities to stimulate new blood vessel growth and can differentiate into lung, liver, heart, brain, bone, cartilage, fat and pancreatic tissue. We believe ERC have the potential to treat a range of diseases, including ischemic conditions, cardiovascular disease, certain neurological diseases, autoimmune diseases (such as Type 1 Diabetes), kidney failure, liver failure, pulmonary diseases and a range of orphan disease indications. ERCs have been cleared by the FDA to begin studies in the United States.

Certain statements herein may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Medistem Inc. These can be identified by the use of forwardlooking words, such as "believes," "expects," "may," "intends," "anticipates," "plans," "estimates," or any other analogous or similar expressions intended to identify forwardlooking statements. These forwardlooking statements and estimates as to future performance, estimates, and other statements contained herein regarding matters that are not historical facts, are only predictions and actual events or results may differ materially. We cannot assure or guarantee that any future results described in this presentation will be achieved, and actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings. The Company undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

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Menstrual Blood Stem Cells Used to Treat Heart Failure Patients

Giving patients stem cells packaged with silica nanoparticles could help doctors determine the effectiveness of the treatments by revealing where the cells go after theyve left the injection needle.

Researchers from Stanford University report in a paper published on Wednesday in the journal Science Translational Medicine that silica nanoparticles taken up by stem cells make the cells visible on ultrasound imaging. While other imaging techniques such as MRI can show where stem cells are located in the body, that method is not as fast, affordable, or widely available as an ultrasound scanner, and more importantly, it does not offer a real-time view of injection, say experts.

Stem cells have significant medical promise because they can be turned into other types of living cell. As well as helping doctors adjust therapeutic dosages in patients, the new technique could help scientists perfect stem cell treatments, says senior author Sanjiv Gambhir. For the most part, researchers shoot blindlythey dont quite know where the cells are going when they are injected, they dont know if they home in to the right target tissue, they dont know if they survive, and they dont know if they leak into other tissue types, says Gambhir.

This, in part, could be slowing advances in stem cell treatments. If stem cells are going to be used as a legitimate medical treatment for the repair of damaged or diseased tissue, then we will need to know precisely where they are going so the treatments can be optimized, says Lara Bogart, a physicist at the University of Liverpool. Bogart is developing magnetic nanoparticles for tracking stem cells using MRI.

To get a better view of where cells are going during and after injection, Gambhir and colleagues used nanoparticles made of silica, a material that reflects sound waves, so it can be detected in an ultrasound scan. The nanoparticles were incubated with mesenchymal stem cells, which can develop into cell types including bone cells, fat cells, and heart cells. The cells ingested the nanoparticles, which did not change the cells growth rate or ability to develop into different cell types. Inside the cells, the nanoparticles clumped together, which made them more visible in an ultrasound.

The researchers then injected the nanoparticle-laden stem cells into the hearts of mice and tracked their movements. Many research groups are testing stem cells as a treatment after a heart attack or for other heart conditions in both lab animals (see A Step Toward Healing Broken Hearts with Stem Cells and Injecting Stem Cells into the Heart Could Stop Chronic Chest Pain) as well as in patients in clinical trials. A fast and real-time imaging tool could help because researchers and doctors need to be sure that the cells reach the most beneficial spots in a sickly heart.

Its very important to know where you inject the cells because you dont want to put them in areas damaged by the heart attack; that tissue is dead and a very hostile environment, says Jeff Bulte, a cell engineer at the Johns Hopkins University School of Medicine who was not involved in the study. On the other hand, you want to place them as close to the site of damage as possible, he says.

The silica nanoparticles can also be detected in MRI machines because they contain a strongly magnetic heavy metal known as gadolinium that shows up in the scans. And they can be detected optically (through microscopes) because they carry a fluorescent dye. This gives us three complementary ways to image the same particle, says Bogart. Depending on the part of the body receiving the transplant, the type of scanner available and the amount of time since injection, a researcher may choose one method over another.

The mice used in the study were healthy, but the team plans to test the tracking method in mice or other lab animals that have heart damage. The team will also use the nanoparticles in different cell types and do more toxicity studies prior to filing for FDA approval to test the nanoparticles in humans. It will be about a three-year process to do first-in-man studies, says Gambhir.

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Future medicine: Stem cells can leverage silica nanoparticles to track where they actually go

Mar. 24, 2013 Stem cells taken from amniotic fluid were used to restore gut structure and function following intestinal damage in rodents, in new research published in the journal Gut. The findings pave the way for a new form of cell therapy to reverse serious damage from inflammation in the intestines of babies.

The study, funded by Great Ormond Street Hospital Children's Charity, investigated a new way to treat necrotizing enterocolitis (NEC), where severe inflammation destroys tissues in the gut. NEC is the most common gastrointestinal surgical emergency in newborn babies, with mortality rates of around 15 to 30 per cent in the UK.

While breast milk and probiotics can help to reduce the incidence of the disease, no medical treatments are currently available other than surgery once NEC sets in. Surgical removal of the dead tissue shortens the bowel and can lead to intestinal failure, with some babies eventually needing ongoing parenteral nutrition (feeding via an intravenous line) or an intestinal transplant.

In the study, led by the UCL Institute of Child Health, amniotic fluid stem (AFS) cells were harvested from rodent amniotic fluid and given to rats with NEC. Other rats with the same condition were given bone marrow stem cells taken from their femurs, or fed as normal with no treatment, to compare the clinical outcomes of different treatments.

NEC-affected rats injected with AFS cells showed significantly higher survival rates a week after being treated, compared to the other two groups. Inspection of their intestines, including with micro magnetic resonance imaging (MRI), showed the inflammation to be significantly reduced, with fewer dead cells, greater self-renewal of the gut tissue and better overall intestinal function.

While bone marrow stem cells have been known to help reverse colonic damage in irritable bowel disease by regenerating tissue, the beneficial effects from stem cell therapy in NEC appear to work via a different mechanism. Following their injection into the gut, the AFS cells moved into the intestinal villi -- the small, finger-like projections that protrude from the lining of the intestinal wall and pass nutrients from the intestine into the blood. However, rather than directly repairing the damaged tissue, the AFS cells appear to have released specific growth factors that acted on progenitor cells in the gut which in turn, reduced the inflammation and triggered the formation of new villi and other tissues.

Dr Paolo De Coppi, UCL Institute of Child Health, who led the study, says: "Stem cells are well known to have anti-inflammatory effects, but this is the first time we have shown that amniotic fluid stem cells can repair damage in the intestines. In the future, we hope that stem cells found in amniotic fluid will be used more widely in therapies and in research, particularly for the treatment of congenital malformations. Although amniotic fluid stem cells have a more limited capacity to develop into different cell types than those from the embryo, they nevertheless show promise for many parts of the body including the liver, muscle and nervous system."

Dr Simon Eaton, UCL Institute of Child Health and co-author of the study, adds: "Once we have a better understanding of the mechanisms by which AFS cells trigger repair and restore function in the gut, we can start to explore new cellular or pharmacological therapies for infants with necrotizing enterocolitis."

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Amniotic fluid stem cells repair gut damage

Stem cells taken from amniotic fluid could offer a way to reverse potentially lethal intestinal damage in newborn babies.

In laboratory experiments, scientists used the cells to restore gut structure and function in rats.

The same technique could pave the way for new treatments for the baby condition necrotising enterocolitis (NEC).

NEC is the most common gastrointestinal emergency affecting newborns, with death rates of 15% to 30% in the UK. Once the condition sets in, no options are currently available other than surgery. Some babies end up having to undergo intestinal transplants.

The new research involved injecting rats with NEC with amniotic fluid stem (AFS) cells. A week later, the animals showed significantly higher survival rates than rats not given the stem cell treatment.

Examination of their guts showed inflammation to be greatly reduced, and signs that the intestine was repairing itself.

Dr Paolo De Coppi, from University College London's Institute of Child Health, who led the study published in the journal Gut, said: "Stem cells are well known to have anti-inflammatory effects, but this is the first time we have shown that amniotic fluid stem cells can repair damage in the intestines.

"In the future, we hope that stem cells found in amniotic fluid will be used more widely in therapies and in research, particularly for the treatment of congenital malformations. Although amniotic fluid stem cells have a more limited capacity to develop into different cell types than those from the embryo, they nevertheless show promise for many parts of the body including the liver, muscle and nervous system."

After their injection into the gut, AFS cells moved into the intestinal villi - small finger-like projections that pass nutrients into the blood. Rather than directly repairing the damaged tissue, they appear to release chemicals that stimulate other progenitor cells.

Co-author Dr Simon Eaton, also from the Institute of Child Health, said: "Once we have a better understanding of the mechanisms by which AFS cells trigger repair and restore function in the gut, we can start to explore new cellular or pharmacological therapies for infants with necrotising enterocolitis."

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Stem cells hope for gut condition

Heart stem cell therapy after a major heart attack holds the promise of helping to repair severely damaged cells by encouraging the growth of new ones. However, the process which involves infusing healthy stem cells into the heart to replace the damaged tissue has had limited success in clinical trials.

In order to get the most benefit from heart stem cell treatment, it is essential for doctors to properly place the cells in the heart. But, once the stem cells are injected, its difficult to determine exactly where they wind up, and many scientists believe faulty placement is ultimately the culprit of the therapys disappointing results.

Now, that problem could be potentially solved with a new visualization technique developed by Dr. Sam Gambhir and fellow researchers at Stanford University School of Medicine in California. Their study, published in Science Translational Medicine, details the invention of silica nanoparticles, which can be injected inside stem cells, acting as tiny tracking devices that allow doctors to see the stem cells path inside the body.

According to the studys researchers, the most encouraging results from heart stem cell therapy have been seen after bypass surgery, which is done right after a patient has suffered a heart attack. If performed correctly, stem cell injections can encourage new cell proliferation and help increase blood flow up to 10 percent.

To get the most benefit, doctors have to find the perfect place in which the cells will do the most work.

The best place is the region (in the heart) between the damaged tissue and the healthy tissue, Jesse Jokerst, a postdoctoral fellow in the Stanford Molecular Imaging Scholars Program and one of the studys authors, told FoxNews.com. Thats where the most therapeutic benefit can occur. When placed there, the stem cells can take advantage of the blood flow in the healthy region, but can effect a change in the diseased region.

In order to determine where to place the cells, physicians currently take images of the heart through magnetic resonance imaging (MRI) one image before the injection to estimate placement, and a second image after the injection to see how the cells have developed. But the time period between the capture of those pictures leaves a lot to be desired, as the stem cells do not have a unique signature that allows doctors to differentiate between them and the normal heart cells.

Feeling somewhat blind, the doctors have many questions once the stem cells are injected. Did they reach their intended target? Did they remain at the heart wall? How many cells actually stayed and how many diffused or died? Inevitably, the doctors have to wait weeks following the stem cell injection to get their questions answered, by observing if heart function improved.

Making a stem cell 'movie'

Frustrated by those time constraints, the researchers realized all their questions could be answered a lot faster and much more accurately through ultrasound imaging.

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New nano-'tracking devices' allow doctors to visualize stem cells inside hearts

Public release date: 20-Mar-2013 [ | E-mail | Share ]

Contact: Bruce Goldman goldmanb@stanford.edu 650-725-2106 Stanford University Medical Center

STANFORD, Calif. The promise of repairing damaged hearts through regenerative medicine infusing stem cells into the heart in the hope that these cells will replace worn out or damaged tissue has yet to meet with clinical success. But a highly sensitive visualization technique developed by Stanford University School of Medicine scientists may help speed that promise's realization.

The technique is described in a study to be published March 20 in Science Translational Medicine. Testing the new imaging method in humans is probably three to five years off.

Human and animal trials in which stem cells were injected into cardiac tissue to treat severe heart attacks or substantial heart failure have largely yielded poor results, said Sam Gambhir, PhD, MD, senior author of the study and professor and chair of radiology. "We're arguing that the failure is at least partly due to faulty initial placement," he said. "You can use ultrasound to visualize the needle through which you deliver stem cells to the heart. But once those cells leave the needle, you've lost track of them."

As a result, key questions go unanswered: Did the cells actually get to the heart wall? If they did, did they stay there, or did they diffuse away from the heart? If they got there and remained there, for how long did they stay alive? Did they replicate and develop into heart tissue?

"All stem cell researchers want to get the cells to the target site, but up until now they've had to shoot blindly," said Gambhir, who is also the Virginia and D.K. Ludwig Professor in Cancer Research and director of the Molecular Imaging Program at Stanford. "With this new technology, they wouldn't have to. For the first time, they would be able to observe in real time exactly where the stem cells they've injected are going and monitor them afterward. If you inject stem cells into a person and don't see improvement, this technique could help you figure out why and tweak your approach to make the therapy better."

Therapeutic stem cells' vague initial positioning is just part of the problem. No "signature" distinguishes these cells from other cells in the patient's body, so once released from the needle tip they can't be tracked afterward. If, in the weeks following stem cells' infusion into the heart, its beating rhythm or pumping prowess has failed to improve so far, more often the case than not you don't know why. That ambiguity, perpetuated by the absence of decent imaging tools, stifles researchers' ability to optimize their therapeutic approach.

The new technique employs a trick that marks stem cells so they can be tracked by standard ultrasound as they're squeezed out of the needle, allowing their more precise guidance to the spot they're intended to go, and then monitored by magnetic-resonance imaging for weeks afterward.

To make this possible, the Gambhir lab designed and produced a specialized imaging agent in the form of nanoparticles whose diameters clustered in the vicinity of just below one-third of a micron less than one-three-thousandth the width of a human hair, or one-thirtieth the diameter of a red blood cell. The acoustical characteristics of the nanoparticles' chief constituent, silica, allowed them to be visualized by ultrasound; they were also doped with the rare-earth element gadolinium, an MRI contrast agent.

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Stem cells entering heart can be tracked with nano-'hitchhikers,' Stanford scientists say

For organisms to develop and grow, asymmetry is essential. New research from Howard Hughes Medical Institute scientists reveals how a localized source of a signaling molecule directs a dividing stem cell to produce two different cellsone identical to its parent, the other a more specialized cell typeand aligns those cells. In a developing tissue, such oriented divisions will position cells to migrate to the right place to ensure the right architecture.

This kind of asymmetry is a universal aspect of how organisms grow, says Roel Nusse, an HHMI investigator at Stanford University, explaining that dividing cells must orient themselves appropriately to create the asymmetrical bodies of complex organisms. In a paper published March 21, 2013, in the journal Science, Nusse and his collaborators show that a protein called Wnt3a coordinates the orientation of the two different cell types that are generated when a dividing stem cell undergoes an asymmetrical division.

Theres all kinds of geometry going on, regulated by the signals between cells. But when you add growth factors to a tissue culture medium, theres no orientation effect. Roel Nusse

Stem cell division with Wnt-3a bead: When grown with a Wnt3a-coated bead (blue), embryonic stem cells divide such that one daughter cell is proximal to the Wnt3a signal, and the other daughter cell is distal to the signal. Segregating chromosomes of the dividing cell are seen in orange.

From: Habib, S.J., Chen, B., Tsai, F., Anastassiadis, K., Meyer, T., Betzig, E., and Nusse, R. 2013. Science.

Wnt3a is one of a large family of Wnt proteins that play important roles in controlling how organisms develop and grow. Nusse and Harold Varmus discovered the first Wnt gene in mice in Varmuss lab at the University of California, San Francisco in 1982. Since then, Nusse and others have shown that Wnt proteins play key roles in embryonic development, tissue regeneration, bone growth, stem cell differentiation, as well as many human cancers.

To study how Wnt proteins affect cells, researchers typically add the molecule to the nutrient-rich solution in which laboratory-cultured cells are grown. Nusse and his team recently showed that when Wnt3a is given to embryonic stem cells in this way, it helps the cells maintain their identity as stem cells, rather than differentiating into more specialized cells. But experiments like these dont really reflect the ways cells in a living organism receive signals, Nusse says.

Most of the signals that cells in tissues make for each other are received by neighboring cells, he says. So theres an orientation effect: the signal comes from one end of the cell and it only activates the target cell at one side. Theres all kinds of geometry going on, regulated by the signals between cells. But when you add growth factors to a tissue culture medium, theres no orientation effect.

Shukry Habib, a postdoctoral researcher in Nusses lab, came up with a way to recreate that orientation effect with cells grown in a dish. Rather than adding Wnt3a to the tissue culture medium, he attached it to tiny beads. When he added the Wnt-coated beads to dishes in which embryonic stem cells were growing, the scientists could then watch individual cells that were close enough to a bead to receive a Wnt3a signal, and track the fate of the new cells as they divided.

Nusse says the first experiments with the Wnt3a beads were underway when he attended a meeting of HHMI scientists and met with Eric Betzig, a lab head at the Janelia Farm Research Campus. In 2011, Betzigs team developed a high-speed, high-resolution, three-dimensional imaging technology that they call the Bessel beam plane illumination microscope. The microscope gives extraordinarily detailed views of cellular processes in action, and as Betzig and Nusse talked, they realized it could be a powerful tool in tracking the stem cells response to the Wnt-coated beads.

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Wnt Signal Regulates the Geometry of Dividing Stem Cells

Mar. 20, 2013 The promise of repairing damaged hearts through regenerative medicine -- infusing stem cells into the heart in the hope that these cells will replace worn out or damaged tissue -- has yet to meet with clinical success. But a highly sensitive visualization technique developed by Stanford University School of Medicine scientists may help speed that promise's realization.

The technique is described in a study published March 20 in Science Translational Medicine. Testing the new imaging method in humans is probably three to five years off.

Human and animal trials in which stem cells were injected into cardiac tissue to treat severe heart attacks or substantial heart failure have largely yielded poor results, said Sam Gambhir, PhD, MD, senior author of the study and professor and chair of radiology. "We're arguing that the failure is at least partly due to faulty initial placement," he said. "You can use ultrasound to visualize the needle through which you deliver stem cells to the heart. But once those cells leave the needle, you've lost track of them."

As a result, key questions go unanswered: Did the cells actually get to the heart wall? If they did, did they stay there, or did they diffuse away from the heart? If they got there and remained there, for how long did they stay alive? Did they replicate and develop into heart tissue?

"All stem cell researchers want to get the cells to the target site, but up until now they've had to shoot blindly," said Gambhir, who is also the Virginia and D.K. Ludwig Professor in Cancer Research and director of the Molecular Imaging Program at Stanford. "With this new technology, they wouldn't have to. For the first time, they would be able to observe in real time exactly where the stem cells they've injected are going and monitor them afterward. If you inject stem cells into a person and don't see improvement, this technique could help you figure out why and tweak your approach to make the therapy better."

Therapeutic stem cells' vague initial positioning is just part of the problem. No "signature" distinguishes these cells from other cells in the patient's body, so once released from the needle tip they can't be tracked afterward. If, in the weeks following stem cells' infusion into the heart, its beating rhythm or pumping prowess has failed to improve -- so far, more often the case than not -- you don't know why. That ambiguity, perpetuated by the absence of decent imaging tools, stifles researchers' ability to optimize their therapeutic approach.

The new technique employs a trick that marks stem cells so they can be tracked by standard ultrasound as they're squeezed out of the needle, allowing their more precise guidance to the spot they're intended to go, and then monitored by magnetic-resonance imaging for weeks afterward.

To make this possible, the Gambhir lab designed and produced a specialized imaging agent in the form of nanoparticles whose diameters clustered in the vicinity of just below one-third of a micron -- less than one-three-thousandth the width of a human hair, or one-thirtieth the diameter of a red blood cell. The acoustical characteristics of the nanoparticles' chief constituent, silica, allowed them to be visualized by ultrasound; they were also doped with the rare-earth element gadolinium, an MRI contrast agent.

The Stanford group showed that mesenchymal stem cells -- a class of cells often used in heart-regeneration research -- were able to ingest and store the nanoparticles without losing any of their ability to survive, replicate and differentiate into living heart cells. The nanoparticles were impregnated with a fluorescent material, so Gambhir's team could determine which mesenchymal stem cells gobbled them up. (Mesenchymal stem cells, which are able to differentiate into beating heart cells, can sometimes be harvested from the very patients about to undergo a procedure. This could, in principle, alleviate concerns about the cells being rejected by a patient's immune system.)

Upon infusing the imaging-agent-loaded stem cells from mice, pigs or humans into the hearts of healthy mice, the scientists could watch the cells via ultrasound after they left the needle tip and, therefore, better direct them to the targeted area of the heart wall. Two weeks later, the team could still get a strong MRI signal from the cells. (Eventually, the continued division of the healthy infused stem cells diluted the signal to below the MRI detection limit.)

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Stem cells entering heart can be tracked with nano-hitchhikers

Mar. 21, 2013 More than 50,000 stem cell transplants are performed each year worldwide. A research team led by Weill Cornell Medical College investigators may have solved a major issue of expanding adult hematopoietic stem cells (HSCs) outside the human body for clinical use in bone marrow transplantation -- a critical step towards producing a large supply of blood stem cells needed to restore a healthy blood system.

In the journal Blood, Weill Cornell researchers and collaborators from Memorial-Sloan Kettering Cancer Center describe how they engineered a protein to amplify adult HSCs once they were extracted from the bone marrow of a donor. The engineered protein maintains the expanded HSCs in a stem-like state -- meaning, they will not differentiate into specialized blood cell types before they are transplanted in the recipient's bone marrow.

Finding a bone marrow donor match is challenging and the number of bone marrow cells from a single harvest procedure are often not sufficient for a transplant. Additional rounds of bone marrow harvest and clinical applications to mobilize blood stem cells are often required.

However, an expansion of healthy HSCs in the lab would mean that fewer stem cells need to be retrieved from donors. It also suggests that adult blood stem cells could be frozen and banked for future expansion and use -- which is not currently possible.

"Our work demonstrates that we can overcome a major technical hurdle in the expansion of adult blood stem cells, making it possible, for the first time, to produce them on an industrial scale," says the study's senior investigator, Dr. Pengbo Zhou, professor of pathology and laboratory medicine at Weill Cornell.

If the technology by Weill Cornell passes future testing hurdles, Dr. Zhou believes bone marrow banks could take a place alongside blood banks.

"The immediate goal is for us to see if we can take fewer blood stem cells from a donor and expand them for transplant. That way more people may be more likely to donate," Dr. Zhou says. "If many people donate, then we can type the cells before we freeze and bank them, so that we will know all the immune characteristics. The hope is that when a patient needs a bone marrow transplant to treat cancer or another disease, we can find the cells that match, expand them and use them."

Eventually, individuals may choose to bank their own marrow for potential future use, Dr. Zhou says. "Not only are a person's own blood stem cells the best therapy for many blood cancers, but they may also be useful for other purposes, such as to slow aging."

A Scrambled Destruction Signal

Bone marrow is the home of HSCs that produce all blood cells, including all types of immune cells. One treatment for patients with blood cancers produced by abnormal blood cells is to remove the unhealthy marrow and transplant healthy blood stem cells from a donor. Patients with some cancers may also need a bone marrow transplant when anticancer treatments damage the blood. Bone marrow transplantation can also be used to treat other disorders, such as immune deficiency disorders.

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New method developed to expand blood stem cells for bone marrow transplant

Public release date: 21-Mar-2013 [ | E-mail | Share ]

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. Cells in the body need to be acutely aware of their surroundings. A signal from one direction may cause a cell to react in a very different way than if it had come from another direction. Unfortunately for researchers, such vital directional cues are lost when cells are removed from their natural environment to grow in an artificial broth of nutrients and growth factors.

Now, researchers at the Stanford University School of Medicine and the Howard Hughes Medical Institute have devised a way to mimic in the laboratory the spatially oriented signaling that cells normally experience.

Using the technique, they've found that the location of a "divide now" signal on the membrane of a human embryonic stem cell governs where in that cell the plane of division occurs. It also determines which of two daughter cells remains a stem cell and which will become a progenitor cell to replace or repair damaged tissue.

The research offers an unprecedented, real-time glimpse into the intimate world of a single stem cell as it decides when and how to divide, and what its daughter cells should become. But the implications stretch beyond stem cells.

"In the body, it is likely that every cell grows and differentiates in some kind of orientation," said Roeland Nusse, PhD, professor of developmental biology. "Without this guidance, specialized cells would end up in the wrong place. Now, we can study the division of single mammalian cells in real time and see them dividing and differentiating in an oriented way."

Understanding this process of self-renewal and specialization (or differentiation) is critical to learning how to truly harness the power of stem cells for future therapies. But polarity, or the ability of a cell to distinguish its top from bottom or left from right, is also vital to many other biological processes. For example, hair grows out of, rather than into, the body, and tissues develop with orderly layers of specific cell types.

Nusse is the senior author of the work, which will be published March 23 in Science. He is also a member of the Stanford Cancer Institute, the Stanford Institute for Stem Cell Biology and Regenerative Medicine and HHMI investigator. Shukry Habib, PhD, a research associate and Siebel Scholar, is the lead author of the work. The study was funded in part by a grant from the California Institute of Regenerative Medicine.

Stem cells are unique in their ability to both self-renew and to generate progenitor cells that can become many cell types. A single stem cell can divide to make two new stem cells or, in a process called asymmetric division, give rise to one stem cell and one progenitor cell. Because the original parent cell is replaced by the two new daughter cells, this approach ensures that stem cells will not be depleted during periods of development or healing.

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Stem cells use signal orientation to guide division, Stanford study shows