dailyfinance.com 2010-04-13 For investors on the hunt for groundbreaking technologies, stem cell therapies originally looked promising. But the world has been waiting for a long time for the basic research to transform into viable therapies, and in the meantime, Wall Street has largely lost interest. Now, however, there's a "disconnect between science and valuation in cell therapies," says Jason Kolbert, an analyst with National Securities. The state of stem cell therapy today is reminiscent of where monoclonal antibody therapy was back in the mid-1990s, after that field had a period of high hopes followed by disappointing results, Kolbert says. Back then, the whole sector's market cap was $1 billion. Now, blockbuster treatments such as Avastin (a product of Roche [RHHBY] subsidiary Genentech) and Rituxan (which Roche markets in partnership with Biogen Idec [BIIB]) have changed all that. Similarly, given the advances in stem cell science in recent years, it is clear to Kolbert "cell therapy is going to be a viable part of our future." The Basics of Stem Cell Therapy Stem cells are unspecialized cells that can develop into many different cell types in the body; in many tissues, they serve as a sort of internal repair system, mainly through division. When a stem cell divides, the new cells can become more specialized cells, such as a muscle cells, red blood cells or brain cells. The idea behind stem cell therapy is to cure diseases by transplanting stem cells into the patient, where they can grow new, specialized cells to replace those which are damaged or defective. Imagine curing a diseased liver by allowing it to grow new tissue, rather than transplanting a whole one; regenerating brain and nerve cells and tissues to treat Alzheimer's or Parkinson's diseases; repairing the effects of spinal cord injuries, heart disease, diabetes, arthritis or burns by giving the body the tools it needs to heal itself. While the use of embryonic stem cells in these therapies has led some to have ethical issues with the treatments, the use of adult stem cells or pluripotent stem cells -- specialized adult cells that can be "reprogrammed" to assume a stem cell-like state -- removed many of those barriers and concerns. The Three Favorites Companies in the field can be differentiated depending on the therapies they're pursuing, the cells they're using, and the manufacturing process or the service they offer. For example, "Replacing diseased tissues with stem cells is the holy grail of regenerative medicine," Kolbert says. "But companies attempting this feat, such as Geron (GERN) (with its spinal chord graft) and StemCells (STEM) (with its liver initiative) face difficult scientific challenges and will take a long time to play out." One hurdle to overcome is developing a way to avoid teratoma -- when stem cells continue to grow and divide beyond the intent of the therapy, essentially creating a cancer. "It's not clear whether StemCells or Geron will ever achieve their goals," says Kolbert. He prefers the companies that use stem cells to alter the micro-environment in the region of injury. Aastrom Biosciences (ASTM) develops therapies for use in the treatment of severe cardiovascular diseases. Recently it reported data from a Phase 2 trial in people with critical limb ischemia showing circulation was restored to many patients facing amputation. "I think it's one of the most significant clinical events that we've seen last year. Interestingly enough, Aastrom's stock price didn't move and no one seems to be taking notice, but the company is still making progress." Athersys (ATHX) has developed its unique off-the-shelf MultiStem platform to treat illnesses including cardiovascular and inflammatory diseases. In December, Athersys signed a global alliance agreement with Pfizer (PFE) for the development and commercialization of MultiStem for the treatment of inflammatory bowel disease. "This just proves MultiStem's potential," Kolbert says. MultiStem is currently being tested in two Phase 1 trials. Although Athersys uses allogeneic cells (cells that are derived from a healthy donor), while Aastrom uses autologous cells (cells that are derived from the patient, treated then re-injected), it has a similar product to Aastrom, so any positive data there should be good for Athersys. Pluristem Therapeutics (PSTI), meanwhile, uses human placental cells to develops therapies to treat degenerative, ischemic and autoimmune disorders. These off-the-shelf, ready-to-use products do not require tissue matching. Its leading candidate is in a Phase 1 trial for peripheral arterial disease. "We expect to see results from several trials of stem cell therapies in the next two to three years. We believe companies such as Athersys, Aastrom and Pluristem, with cells that promote local healing and clear from circulation without tissue integration, are most likely to be successful," Kolbert says. A Chance to Buy in Ahead of the Curve -- If You're Willing to Take Some Risk "You can buy the entire sector for about $1.6 billion. If you took out market leaders Geron and Osiris, you can buy the entire space for $500 million. That's shocking for a space with the potential to revolutionize medicine as we know it today." "Seeing Pfizer invest in the space, Genzyme's (GENZ) bet with Osiris Therapeutics (OSIR) (which recently had a setback when two of its Phase 3 trials did not meet their end points) and the fact that Celgene (CELG) is getting deeper into the space means that the larger companies want to stake out a piece for themselves for the future -- a bullish sign." "I'm seeing enough clinical trial progress in companies like Athersys and Aastrom that I believe that the stage is being set for successful data over the next two to three years," says Kolbert. Some investors might indeed think it's a great time to buy in ahead of the curve, but keep in mind that even Kolbert doesn't expect any products on the market for the next three to five years, and that most of the companies are very small, making them riskier and more speculative by nature.

ScienceDaily (Mar. 30, 2010) — Scientists seeking new ways to fight maladies ranging from arthritis and osteoporosis to broken bones that won’t heal have cleared a formidable hurdle, pinpointing and controlling a key molecular player to keep stem cells in a sort of extended infancy. It’s a step that makes treatment with the cells in the future more likely for patients.

Controlling and delaying development of the cells, known as mesenchymal (pronounced meh-ZINK-a-mill) stem cells, is a long-sought goal for researchers. It’s a necessary step for doctors who would like to expand the number of true skeletal stem cells available for a procedure before the cells start becoming specific types of cells that may — or may not — be needed in a patient with, say, weak bones from osteoporosis, or an old knee injury.

“A big problem has been that these stem cells like to differentiate rapidly — oftentimes too rapidly to make them very useful,” said Matthew J. Hilton, Ph.D., the leader of the team at the University of Rochester Medical Center. “It’s been very hard to get a useful number of stem cells that can still become any one of several types of tissue a patient might need. Having a large population of true skeletal stem cells available is a key consideration for new therapies, and that’s been a real roadblock thus far.”

In a study published online in the journal Development, Hilton’s team discussed how it was able to increase the number and delay the development of stem cells that create bones, cartilage, muscle and fat. The first authors of the paper are Yufeng Dong, Ph.D., senior instructor, and technician Alana Jesse, who worked in Hilton’s laboratory at the Center for Musculoskeletal Research.

Hilton’s team showed in mice that a molecule called Notch, which is well known for the influence it wields on stem cells that form the blood and the nervous system, is a key factor in the development of mesenchymal stem cells, which make up a tiny fraction of the cells in the bone marrow and other tissues.

The team showed that Notch prevents stem cells from maturing. When the scientists activated the Notch pathway, the stem cells didn’t progress as usual. Instead, they remained indefinitely in an immature state and did not go on to become bone cells, cartilage cells, or cells for connective tissue.

The team also settled a long-standing question, fingering the molecule RBPJ-kappa as the molecule through which Notch works in mesenchymal stem cells. That knowledge is crucial for scientists trying to understand precisely how Notch works in bone and cartilage development. A few years ago, Hilton was part of a team that showed that Notch is a critical regulator of the development of bone and cartilage. The latest study extends those observations, providing important details that suggest appropriate activation and manipulation of the Notch pathway may provide doctors with a tool to maintain and expand mesenchymal stem cells for use in treating disease.

The work is part of ongoing research around the world aimed at harnessing the promise of stem cells for human health. Unfortunately, stem cell therapy has been slow to actually make a difference in the lives of patients with problems of the bones and cartilage, Hilton notes, largely because so many questions are currently unanswered.

“To really make stem-cell medicine work, we need to understand where the stem cells have come from and how to get them to become the cell you want, when and where you want it. We are definitely in the infancy of learning how to manipulate stem cells and use them in treatment,” said Hilton, assistant professor of Orthopaedics and Rehabilitation.

“This research helps set the foundation for ultimately trying new therapies in patients,” he added. “For instance, let’s say a patient has a fracture that simply won’t heal. The patient comes in and has a sample of bone marrow drawn. Their skeletal stem cells are isolated and expanded in the laboratory via controlled Notch activation, then put back into the patient to create new bone in numbers great enough to heal the fracture. That’s the hope.”

Work in Hilton’s laboratory was initially funded through start-up funds from the medical center. The early findings have helped him attract two grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, and the University has filed a patent on the Notch technology.

In addition to Dong, Jesse, and Hilton, authors include M.D./Ph.D. graduate students Anat Kohn and Lea Gunnell; and faculty members Regis J. O’Keefe, M.D., Ph.D., and Michael Zuscik, Ph.D. Tasuko Honjo of the Kyoto University Graduate School of Medicine also contributed.

ScienceDaily (Mar. 30, 2010) — Scientists seeking new ways to fight maladies ranging from arthritis and osteoporosis to broken bones that won't heal have cleared a formidable hurdle, pinpointing and controlling a key molecular player to keep stem cells in a sort of extended infancy. It's a step that makes treatment with the cells in the future more likely for patients. Controlling and delaying development of the cells, known as mesenchymal (pronounced meh-ZINK-a-mill) stem cells, is a long-sought goal for researchers. It's a necessary step for doctors who would like to expand the number of true skeletal stem cells available for a procedure before the cells start becoming specific types of cells that may -- or may not -- be needed in a patient with, say, weak bones from osteoporosis, or an old knee injury. "A big problem has been that these stem cells like to differentiate rapidly -- oftentimes too rapidly to make them very useful," said Matthew J. Hilton, Ph.D., the leader of the team at the University of Rochester Medical Center. "It's been very hard to get a useful number of stem cells that can still become any one of several types of tissue a patient might need. Having a large population of true skeletal stem cells available is a key consideration for new therapies, and that's been a real roadblock thus far." In a study published online in the journal Development, Hilton's team discussed how it was able to increase the number and delay the development of stem cells that create bones, cartilage, muscle and fat. The first authors of the paper are Yufeng Dong, Ph.D., senior instructor, and technician Alana Jesse, who worked in Hilton's laboratory at the Center for Musculoskeletal Research. Hilton's team showed in mice that a molecule called Notch, which is well known for the influence it wields on stem cells that form the blood and the nervous system, is a key factor in the development of mesenchymal stem cells, which make up a tiny fraction of the cells in the bone marrow and other tissues. The team showed that Notch prevents stem cells from maturing. When the scientists activated the Notch pathway, the stem cells didn't progress as usual. Instead, they remained indefinitely in an immature state and did not go on to become bone cells, cartilage cells, or cells for connective tissue. The team also settled a long-standing question, fingering the molecule RBPJ-kappa as the molecule through which Notch works in mesenchymal stem cells. That knowledge is crucial for scientists trying to understand precisely how Notch works in bone and cartilage development. A few years ago, Hilton was part of a team that showed that Notch is a critical regulator of the development of bone and cartilage. The latest study extends those observations, providing important details that suggest appropriate activation and manipulation of the Notch pathway may provide doctors with a tool to maintain and expand mesenchymal stem cells for use in treating disease. The work is part of ongoing research around the world aimed at harnessing the promise of stem cells for human health. Unfortunately, stem cell therapy has been slow to actually make a difference in the lives of patients with problems of the bones and cartilage, Hilton notes, largely because so many questions are currently unanswered. "To really make stem-cell medicine work, we need to understand where the stem cells have come from and how to get them to become the cell you want, when and where you want it. We are definitely in the infancy of learning how to manipulate stem cells and use them in treatment," said Hilton, assistant professor of Orthopaedics and Rehabilitation. "This research helps set the foundation for ultimately trying new therapies in patients," he added. "For instance, let's say a patient has a fracture that simply won't heal. The patient comes in and has a sample of bone marrow drawn. Their skeletal stem cells are isolated and expanded in the laboratory via controlled Notch activation, then put back into the patient to create new bone in numbers great enough to heal the fracture. That's the hope." Work in Hilton's laboratory was initially funded through start-up funds from the medical center. The early findings have helped him attract two grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, and the University has filed a patent on the Notch technology. In addition to Dong, Jesse, and Hilton, authors include M.D./Ph.D. graduate students Anat Kohn and Lea Gunnell; and faculty members Regis J. O'Keefe, M.D., Ph.D., and Michael Zuscik, Ph.D. Tasuko Honjo of the Kyoto University Graduate School of Medicine also contributed.

ScienceDaily (Mar. 31, 2010) — A novel stem cell therapy that arms the immune system with an intrinsic defence against HIV could be a powerful strategy to tackle the disease.

Professor Ben Berkhout speaking at the Society for General Microbiology’s spring meeting in Edinburgh explains how this new approach could dramatically improve the quality of life and life expectancy for HIV sufferers in whom antiviral drugs are no longer effective.

In the absence of an effective vaccine, daily administration of anti-retroviral drugs is the most effective treatment for HIV. However, low patient compliance rates combined with the virus’s ability to easily mutate has led to the emergence of drug-resistant strains that are difficult to treat.

Professor Berkhout from the University of Amsterdam is investigating a novel gene therapy that has long-lasting effects even after a single treatment. It involves delivering antiviral DNA to the patients’ own immune cells that arms them against viral infection. “This therapy would offer an alternative for HIV-infected patients that can no longer be treated with regular antivirals,” he suggested.

The therapy involves extracting and purifying blood stem cells from the patient’s bone marrow. Antiviral DNA is transferred to the cells in the laboratory, after which the cells are re-injected into the body. The DNA encodes tiny molecules called small RNAs that are the mirror image of key viral genes used by HIV to cause disease. The small RNAs float around inside the immune cell until they encounter viral genes which they can stick to like Velcro™. This mechanism, called ‘RNA interference’ can block the production of key viral components from these genes.

Transferring the antiviral DNA to stem cells would help to restore a large part of the patient’s immune system. “Stem cells are the continually dividing ‘master copy’ cells from which all other immune cells are derived. By engineering the stem cells, the antiviral DNA is inherited by all the immune cells that are born from it,” explained Professor Berkhout.

The group hopes to start clinical trials of the therapy within 3 years. “So far, very promising results have been obtained in the laboratory, and we are now testing the safety and efficacy in a pre-clinical mouse model,” said Professor Berkhout.

ScienceDaily (Mar. 31, 2010) — A novel stem cell therapy that arms the immune system with an intrinsic defence against HIV could be a powerful strategy to tackle the disease. Professor Ben Berkhout speaking at the Society for General Microbiology's spring meeting in Edinburgh explains how this new approach could dramatically improve the quality of life and life expectancy for HIV sufferers in whom antiviral drugs are no longer effective. In the absence of an effective vaccine, daily administration of anti-retroviral drugs is the most effective treatment for HIV. However, low patient compliance rates combined with the virus's ability to easily mutate has led to the emergence of drug-resistant strains that are difficult to treat. Professor Berkhout from the University of Amsterdam is investigating a novel gene therapy that has long-lasting effects even after a single treatment. It involves delivering antiviral DNA to the patients' own immune cells that arms them against viral infection. "This therapy would offer an alternative for HIV-infected patients that can no longer be treated with regular antivirals," he suggested. The therapy involves extracting and purifying blood stem cells from the patient's bone marrow. Antiviral DNA is transferred to the cells in the laboratory, after which the cells are re-injected into the body. The DNA encodes tiny molecules called small RNAs that are the mirror image of key viral genes used by HIV to cause disease. The small RNAs float around inside the immune cell until they encounter viral genes which they can stick to like Velcro™. This mechanism, called 'RNA interference' can block the production of key viral components from these genes. Transferring the antiviral DNA to stem cells would help to restore a large part of the patient's immune system. "Stem cells are the continually dividing 'master copy' cells from which all other immune cells are derived. By engineering the stem cells, the antiviral DNA is inherited by all the immune cells that are born from it," explained Professor Berkhout. The group hopes to start clinical trials of the therapy within 3 years. "So far, very promising results have been obtained in the laboratory, and we are now testing the safety and efficacy in a pre-clinical mouse model," said Professor Berkhout.

April 13, 2010

Procedure that worked on Montreal man a possible alternative to transplants

Injecting stem cells into a Montreal man’s heart seems to have helped heal the organ, say researchers investigating the experimental procedure.

The case is part of the first study in Canada to evaluate the safety and feasibility of injecting different stem cells into heart patients.

Patients who have a coronary artery bypass have blood coming back to the heart, but the problem is, there’s nothing to generate the heart muscle, said Dr. Nicolas Noiseux, cardiac surgeon at the University of Montreal Hospital Centre and principal investigator in the study.

“This is why we want to have the stem cells plus the bypass in order to improve cardiac repair and cardiac function,” Noiseux said.

Researchers used bone marrow from the man’s hip to isolate stem cells, which were purified and enriched in the lab, and then injected directly into his failing heart through a catheter.

Jean-Paul Tremblay, a 59-year-old construction worker, is believed to be the first patient in Canada to have his heart injected with his own stem cells during open-heart bypass surgery for chronic heart failure, Noiseux said.

Heart transplant alternative?

Before the double bypass and stem cell injection, Tremblay said he could barely walk and had no energy. Sitting on the edge of his hospital bed Tuesday, Tremblay said he doesn’t feel tired and is ready to go for a walk.

“I’m in near perfect shape,” Tremblay said in French.

Doctors have noticed improvements in the heart’s capacity to contract, which has improved its ability to pump blood.

The new procedure is less invasive and less expensive than heart transplant, the only treatment currently available for patients with severe heart failure, the hospital said.

Until now, no Canadian research team had performed such a complete treatment process, the hospital said. The process involved:

• Harvesting stem cells from bone marrow
• Sending the cells to Dr. Denis Claude Roy at Maisonneuve-Rosemont Hospital to isolate the most immature stem cells.
• Injecting the stem cells directly into the heart muscle.
• Using cutting-edge imaging techniques to see whether the stem cells are working.

The researchers plan to recruit 20 patients throughout Quebec for the first phase of the study, which will examine heart muscle failure caused by coronary artery disease.

Researchers at Toronto General Hospital also plan to participate in the trial.

If the collaborative research shows the stem cells are regenerative, doctors would have a new tool to help patients facing end-stage heart failure, said cardiac surgeon Dr. Richard Weisel, director of the Toronto General Research Institute.

The Toronto team is waiting for approval to conduct the research using a new-generation device to separate stem cells before they start recruiting patients.

April 13, 2010 Procedure that worked on Montreal man a possible alternative to transplants   Injecting stem cells into a Montreal man's heart seems to have helped heal the organ, say researchers investigating the experimental procedure. The case is part of the first study in Canada to evaluate the safety and feasibility of injecting different stem cells into heart patients. Patients who have a coronary artery bypass have blood coming back to the heart, but the problem is, there's nothing to generate the heart muscle, said Dr. Nicolas Noiseux, cardiac surgeon at the University of Montreal Hospital Centre and principal investigator in the study. "This is why we want to have the stem cells plus the bypass in order to improve cardiac repair and cardiac function," Noiseux said. Researchers used bone marrow from the man's hip to isolate stem cells, which were purified and enriched in the lab, and then injected directly into his failing heart through a catheter. Jean-Paul Tremblay, a 59-year-old construction worker, is believed to be the first patient in Canada to have his heart injected with his own stem cells during open-heart bypass surgery for chronic heart failure, Noiseux said. Heart transplant alternative? Before the double bypass and stem cell injection, Tremblay said he could barely walk and had no energy. Sitting on the edge of his hospital bed Tuesday, Tremblay said he doesn't feel tired and is ready to go for a walk. "I'm in near perfect shape," Tremblay said in French. Doctors have noticed improvements in the heart's capacity to contract, which has improved its ability to pump blood. The new procedure is less invasive and less expensive than heart transplant, the only treatment currently available for patients with severe heart failure, the hospital said. Until now, no Canadian research team had performed such a complete treatment process, the hospital said. The process involved: Harvesting stem cells from bone marrow Sending the cells to Dr. Denis Claude Roy at Maisonneuve-Rosemont Hospital to isolate the most immature stem cells. Injecting the stem cells directly into the heart muscle. Using cutting-edge imaging techniques to see whether the stem cells are working. The researchers plan to recruit 20 patients throughout Quebec for the first phase of the study, which will examine heart muscle failure caused by coronary artery disease. Researchers at Toronto General Hospital also plan to participate in the trial. If the collaborative research shows the stem cells are regenerative, doctors would have a new tool to help patients facing end-stage heart failure, said cardiac surgeon Dr. Richard Weisel, director of the Toronto General Research Institute. The Toronto team is waiting for approval to conduct the research using a new-generation device to separate stem cells before they start recruiting patients.

ScienceDaily (Apr. 12, 2010) — Scientists at The Scripps Research Institute have solved the decade-old mystery of why human embryonic stem cells are so difficult to culture in the laboratory, providing scientists with useful new techniques and moving the field closer to the day when stem cells can be used for therapeutic purposes.

The research is being published in the journal Proceedings of the National Academy of Sciences (PNAS) during the week of April 12, 2010.

“This paper addresses a long-standing mystery,” said Scripps Research Associate Professor Sheng Ding, who is senior author of the paper. “Scientists have been puzzled by why human embryonic stem cells die at a critical step in the culture process. In addition to posing a question in fundamental biology, this created a huge technical challenge in the lab.”

The new paper, however, provides elegant solutions to both aspects of this problem.

In the study, the team discovered two novel synthetic small molecule drugs that can be added to human stem cell culture that each individually prevent the death of these cells. The team also unravels the mechanisms by which the compounds promote stem cell survival, shedding light on a previously unknown aspect of stem cell biology.

Notorious Fragility

The hope of most researchers in the field is that one day it will be possible to use stem cells — which possess the ability to develop into many other distinct cell types, such as nerve, heart, or lung cells — to repair damaged tissue from any number of diseases, from Type 1 diabetes to Parkinson’s disease, as well as from injuries.

Laboratory work with human embryonic stem cells, however, has been hampered by their notorious fragility. In the process of growing stem cells in culture, scientists must split off cells from their cell colonies. At this point in the process, however, human embryonic stem cells die unless the scientists take extraordinary care that this does not happen.

“The current techniques to keep these cells alive are tedious and labor-intensive,” said Ding. “Keeping the cells alive is so difficult that some people are discouraged from entering the field. It is very frustrating experience for everyone.”

Mysteriously, mouse embryonic stem cells — which share much basic biology with human embryonic stem cells — do not pose the same difficulties in the laboratory. They can usually be split off from a colony and go on to survive and thrive.

To address these issues, the scientists decided to start with a screen of a library of chemical compounds to see if they could find any small molecules that could be added to the human embryonic stem cell culture that would promote the cells’ survival.

When the scientists examined their results, they were elated to find two novel compounds (named Thiazovivin and Pyrintegrin) that both worked to dramatically protect the cells, promoting human embryonic stem cell survival by more than 30 fold.

“Basically, this solved this cell survival problem that has been plaguing scientists for more than 10 years,” said Ding.

The Importance of Interaction

But the scientists didn’t stop there.

Next, using the two new survival-promoting small molecules as clues, the scientists set out to understand the biological mechanism behind the cells’ survival or demise. By examining cell growth in the presence and absence of the compounds, the team found that the key factor was a protein on the cell surface called e-cadherin, which mediates interactions among cells and between cells and the extracellular matrix (a structure present between a variety of animal cells that provides support and anchorage for cells and regulates intercellular communication).

“While in the past people have often talked about the proteins in cell nucleus as regulating stem cell function, our study puts the focus on a different area,” said Ding. “E-cadherin is a protein on the cell surface that is very important to cell survival and cell growth.”

The team found that when human embryonic stem cells are cut out from the colony, this key protein is disrupted and then internalized within the cell. Without e-cadherin on the cell surface, cell signaling between the cells and their environment is disrupted and the cells quickly die.

Both chemical compounds identified by the study, however, protected e-cadherin from damage.

In further experiments, the scientists found that the key difference between human and mouse embryonic stem cells lay not only within the cells themselves, but also in and controlled by their microenvironment — the surrounding cells, signaling factors, and extracellular matrix. The scientists were able to transfer human embryonic stem cells into a mouse embryonic stem cell microenvironment. There, the scientists found, human cells were more likely to survive, even without the survival-promoting compounds.

Moreover, when the scientists chemically induced human embryonic stem cells back to an earlier stage of development — which had an extracellular environment similar to mouse embryonic stem cells conventionally used in the laboratory — there were also no longer problems growing them in culture.

“This validated our mechanistic investigations from a different angle,” said Ding, “showing that we had dissected out a very core regulatory mechanism.”

Ding expects that the methods discussed in the new study will soon be widely adopted by stem cell laboratories around the world.

“My lab currently uses the novel small molecules identified in this study on a routine basis, making our life significantly easier and advancing our efforts,” said Ding. “Even more, chemically inducing human embryonic stem cells back to an earlier stage of development has advantages for some areas of investigation.”

The first author of the paper, “Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules,” is Yue Xu of Scripps Research. In addition to Ding, other authors include Xiuwen Zhu, Heung Sik Hahm, and Wanguo Wei of Scripps Research and Ergeng Hao and Alberto Hayek of the University of California, San Diego.

The research was supported by grants from The Scripps Research Institute.

ScienceDaily (Apr. 12, 2010) — Scientists at The Scripps Research Institute have solved the decade-old mystery of why human embryonic stem cells are so difficult to culture in the laboratory, providing scientists with useful new techniques and moving the field closer to the day when stem cells can be used for therapeutic purposes. The research is being published in the journal Proceedings of the National Academy of Sciences (PNAS) during the week of April 12, 2010. "This paper addresses a long-standing mystery," said Scripps Research Associate Professor Sheng Ding, who is senior author of the paper. "Scientists have been puzzled by why human embryonic stem cells die at a critical step in the culture process. In addition to posing a question in fundamental biology, this created a huge technical challenge in the lab." The new paper, however, provides elegant solutions to both aspects of this problem. In the study, the team discovered two novel synthetic small molecule drugs that can be added to human stem cell culture that each individually prevent the death of these cells. The team also unravels the mechanisms by which the compounds promote stem cell survival, shedding light on a previously unknown aspect of stem cell biology.   Notorious Fragility   The hope of most researchers in the field is that one day it will be possible to use stem cells -- which possess the ability to develop into many other distinct cell types, such as nerve, heart, or lung cells -- to repair damaged tissue from any number of diseases, from Type 1 diabetes to Parkinson's disease, as well as from injuries. Laboratory work with human embryonic stem cells, however, has been hampered by their notorious fragility. In the process of growing stem cells in culture, scientists must split off cells from their cell colonies. At this point in the process, however, human embryonic stem cells die unless the scientists take extraordinary care that this does not happen. "The current techniques to keep these cells alive are tedious and labor-intensive," said Ding. "Keeping the cells alive is so difficult that some people are discouraged from entering the field. It is very frustrating experience for everyone." Mysteriously, mouse embryonic stem cells -- which share much basic biology with human embryonic stem cells -- do not pose the same difficulties in the laboratory. They can usually be split off from a colony and go on to survive and thrive. To address these issues, the scientists decided to start with a screen of a library of chemical compounds to see if they could find any small molecules that could be added to the human embryonic stem cell culture that would promote the cells' survival. When the scientists examined their results, they were elated to find two novel compounds (named Thiazovivin and Pyrintegrin) that both worked to dramatically protect the cells, promoting human embryonic stem cell survival by more than 30 fold. "Basically, this solved this cell survival problem that has been plaguing scientists for more than 10 years," said Ding.   The Importance of Interaction   But the scientists didn't stop there. Next, using the two new survival-promoting small molecules as clues, the scientists set out to understand the biological mechanism behind the cells' survival or demise. By examining cell growth in the presence and absence of the compounds, the team found that the key factor was a protein on the cell surface called e-cadherin, which mediates interactions among cells and between cells and the extracellular matrix (a structure present between a variety of animal cells that provides support and anchorage for cells and regulates intercellular communication). "While in the past people have often talked about the proteins in cell nucleus as regulating stem cell function, our study puts the focus on a different area," said Ding. "E-cadherin is a protein on the cell surface that is very important to cell survival and cell growth." The team found that when human embryonic stem cells are cut out from the colony, this key protein is disrupted and then internalized within the cell. Without e-cadherin on the cell surface, cell signaling between the cells and their environment is disrupted and the cells quickly die. Both chemical compounds identified by the study, however, protected e-cadherin from damage. In further experiments, the scientists found that the key difference between human and mouse embryonic stem cells lay not only within the cells themselves, but also in and controlled by their microenvironment -- the surrounding cells, signaling factors, and extracellular matrix. The scientists were able to transfer human embryonic stem cells into a mouse embryonic stem cell microenvironment. There, the scientists found, human cells were more likely to survive, even without the survival-promoting compounds. Moreover, when the scientists chemically induced human embryonic stem cells back to an earlier stage of development -- which had an extracellular environment similar to mouse embryonic stem cells conventionally used in the laboratory -- there were also no longer problems growing them in culture. "This validated our mechanistic investigations from a different angle," said Ding, "showing that we had dissected out a very core regulatory mechanism." Ding expects that the methods discussed in the new study will soon be widely adopted by stem cell laboratories around the world. "My lab currently uses the novel small molecules identified in this study on a routine basis, making our life significantly easier and advancing our efforts," said Ding. "Even more, chemically inducing human embryonic stem cells back to an earlier stage of development has advantages for some areas of investigation." The first author of the paper, "Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules," is Yue Xu of Scripps Research. In addition to Ding, other authors include Xiuwen Zhu, Heung Sik Hahm, and Wanguo Wei of Scripps Research and Ergeng Hao and Alberto Hayek of the University of California, San Diego. The research was supported by grants from The Scripps Research Institute.

ROME — The Vatican is pushing for research of adult stem cells as an alternative to the use of embryonic stem cells, which the Catholic Church opposes because it maintains that the destruction of the embryo amounts to the killing of human life.

On Friday, the Catholic Church threw its support and resources behind the study of intestinal adult stem cells by a group of experts led by the University of Maryland School of Medicine. The group wants to explore the potential use of those cells in the treatment of intestinal and possibly other diseases, and is seeking an initial $2.7 million to get the project going, officials said.

“This research protects life,” Cardinal Renato Martino said during a meeting with Italian and American scientists and health officials to outline the project. “I want to stress that it doesn’t involve embryonic stem cells, where one helps oneself and then throws the embryo away and kills a human life.”

The church is opposed to embryonic stem cell research because it involves the destruction of embryos, but it supports the use of adult stem cells, which are found in the bodies of all humans. Human embryonic stem cells are produced from surplus embryos of in vitro fertilization procedures used to help infertile women get pregnant.

Both are prized for their ability to morph into other kinds of cells, offering the possibility of replacing tissue damaged by ailments such as Parkinson’s disease.

But adult cells are thought to be less versatile than embryonic ones, and scientists have had more trouble growing adult stem cells in the laboratory than embryonic cells.

Still, adult stem cells could be easier to use if they are taken from patients themselves, because the replacement tissue would have less chance of being rejected.

Cardinal Renato Martino joined a meeting at Rome’s National Institute of Health. The Vatican is pushing for research of adult stem cells as an alternative to the use of embryonic stem cells.

Martino, a powerful cardinal and retired head of the Pontifical Council for Justice and Peace, told The Associated Press after the meeting that he had “no doubt” that the Vatican would help finance the project through its Rome hospital, Bambin Gesu, and other funding. The exact amount and modalities will be worked out in future meetings with the University of Maryland and other scientists involved in the project.

In 2007, Pope Benedict XVI said the Catholic Church can encourage somatic stem cell research — also known as adult stem cell research — “because of the favorable results obtained through these alternative methods,” and more importantly because it respects “the life of the human being at every stage of his or her existence.”

During his visit to Washington last year, Benedict underscored his beliefs about stem cells by giving President Barack Obama a copy of a Vatican document on bioethics that hardened the church’s opposition to using embryos for stem cell research, cloning and in-vitro fertilization.

Obama has lifted restrictions, imposed by his predecessor President George W. Bush, on federal funding of research using human embryonic stem cells.

The Vatican has drawn criticism for its opposition to embryonic stem cell research. But it insists there are scientifically viable alternatives and that the efforts of the scientific community should go in that direction.

Supporting this university project is part of those efforts.

“Ethically, the rules the Catholic Church promotes are really very simple: That all research be respectful of human life,” said Father Bob Gahl, an American professor of Moral Philosophy at the Pontifical University of the Holy Cross. “Nobody should be killed in the process of doing medical research. So this new project falls exactly within the Catholic Church’s ethical guidelines.”

Dr. George Daley, a stem cell expert at Children’s Hospital in Boston and past president of the International Society for Stem Cell Research, said both adult and embryonic stem cells may prove useful for treating different diseases.

“I applaud the Vatican for being interested in supporting biomedical research,” Daley said Friday, “but I can’t help but think there’s an agenda.”

He called intestinal stem cells “a very exciting area of basic research” but said therapeutic uses are only speculative at this point.

Researchers involved in the Vatican-backed project are convinced that intestinal stem cells — a relatively new field —hold promise and want to assess their potential for therapeutic use.

“We want to harvest them, we want to isolate them, we want to make them grow outside our body,” and transform them into cells of any kind, said Alessio Fasano, the scientist leading the project and the director of the University of Maryland’s Center for Celiac Research.

“If we reach that phase, if we are able to achieve that goal, then our next step is to eventually move to clinical application,” Fasano told the AP before Friday’s announcement.

Intestinal stem cells have certain features that make them appealing for this kind of research, Fasano said.

They are very active cells — the intestine replenishes all its cells every few days — and they are intrinsically flexible — already programmed to generate all the various kinds of cells such as mucus cells or epithelial cells present in the highly complex organ. Furthermore, harvesting them can be done through a routine medical procedure, Fasano noted.

Fasano said his team hopes to decide about the feasibility of the project within the next two to three years. He said the network of experts, expected to be around 40 people, would work at their respective facilities, sharing information and the workload to speed up the process.

ROME — The Vatican is pushing for research of adult stem cells as an alternative to the use of embryonic stem cells, which the Catholic Church opposes because it maintains that the destruction of the embryo amounts to the killing of human life. On Friday, the Catholic Church threw its support and resources behind the study of intestinal adult stem cells by a group of experts led by the University of Maryland School of Medicine. The group wants to explore the potential use of those cells in the treatment of intestinal and possibly other diseases, and is seeking an initial $2.7 million to get the project going, officials said. "This research protects life," Cardinal Renato Martino said during a meeting with Italian and American scientists and health officials to outline the project. "I want to stress that it doesn't involve embryonic stem cells, where one helps oneself and then throws the embryo away and kills a human life." The church is opposed to embryonic stem cell research because it involves the destruction of embryos, but it supports the use of adult stem cells, which are found in the bodies of all humans. Human embryonic stem cells are produced from surplus embryos of in vitro fertilization procedures used to help infertile women get pregnant. Both are prized for their ability to morph into other kinds of cells, offering the possibility of replacing tissue damaged by ailments such as Parkinson's disease. But adult cells are thought to be less versatile than embryonic ones, and scientists have had more trouble growing adult stem cells in the laboratory than embryonic cells. Still, adult stem cells could be easier to use if they are taken from patients themselves, because the replacement tissue would have less chance of being rejected.       Cardinal Renato Martino joined a meeting at Rome's National Institute of Health. The Vatican is pushing for research of adult stem cells as an alternative to the use of embryonic stem cells.   Martino, a powerful cardinal and retired head of the Pontifical Council for Justice and Peace, told The Associated Press after the meeting that he had "no doubt" that the Vatican would help finance the project through its Rome hospital, Bambin Gesu, and other funding. The exact amount and modalities will be worked out in future meetings with the University of Maryland and other scientists involved in the project. In 2007, Pope Benedict XVI said the Catholic Church can encourage somatic stem cell research — also known as adult stem cell research — "because of the favorable results obtained through these alternative methods," and more importantly because it respects "the life of the human being at every stage of his or her existence." During his visit to Washington last year, Benedict underscored his beliefs about stem cells by giving President Barack Obama a copy of a Vatican document on bioethics that hardened the church's opposition to using embryos for stem cell research, cloning and in-vitro fertilization. Obama has lifted restrictions, imposed by his predecessor President George W. Bush, on federal funding of research using human embryonic stem cells. The Vatican has drawn criticism for its opposition to embryonic stem cell research. But it insists there are scientifically viable alternatives and that the efforts of the scientific community should go in that direction. Supporting this university project is part of those efforts. "Ethically, the rules the Catholic Church promotes are really very simple: That all research be respectful of human life," said Father Bob Gahl, an American professor of Moral Philosophy at the Pontifical University of the Holy Cross. "Nobody should be killed in the process of doing medical research. So this new project falls exactly within the Catholic Church's ethical guidelines." Dr. George Daley, a stem cell expert at Children's Hospital in Boston and past president of the International Society for Stem Cell Research, said both adult and embryonic stem cells may prove useful for treating different diseases. "I applaud the Vatican for being interested in supporting biomedical research," Daley said Friday, "but I can't help but think there's an agenda." He called intestinal stem cells "a very exciting area of basic research" but said therapeutic uses are only speculative at this point. Researchers involved in the Vatican-backed project are convinced that intestinal stem cells — a relatively new field —hold promise and want to assess their potential for therapeutic use. "We want to harvest them, we want to isolate them, we want to make them grow outside our body," and transform them into cells of any kind, said Alessio Fasano, the scientist leading the project and the director of the University of Maryland's Center for Celiac Research. "If we reach that phase, if we are able to achieve that goal, then our next step is to eventually move to clinical application," Fasano told the AP before Friday's announcement. Intestinal stem cells have certain features that make them appealing for this kind of research, Fasano said. They are very active cells — the intestine replenishes all its cells every few days — and they are intrinsically flexible — already programmed to generate all the various kinds of cells such as mucus cells or epithelial cells present in the highly complex organ. Furthermore, harvesting them can be done through a routine medical procedure, Fasano noted. Fasano said his team hopes to decide about the feasibility of the project within the next two to three years. He said the network of experts, expected to be around 40 people, would work at their respective facilities, sharing information and the workload to speed up the process.  

BUFFALO, N.Y. — Biomedical researchers at the University at Buffalo have engineered adult stem cells that scientists can grow continuously in culture, a discovery that could speed development of cost-effective treatments for diseases including heart disease, diabetes, immune disorders and neurodegenerative diseases.

UB scientists created the new cell lines – named “MSC Universal” – by genetically altering mesenchymal stem cells, which are found in bone marrow and can differentiate into cell types including bone, cartilage, muscle, fat, and beta-pancreatic islet cells.

The researchers say the breakthrough overcomes a frustrating barrier to progress in the field of regenerative medicine: The difficulty of growing adult stem cells for clinical applications.

Because mesenchymal stem cells have a limited life span in laboratory cultures, scientists and doctors who use the cells in research and treatments must continuously obtain fresh samples from bone marrow donors, a process both expensive and time-consuming. In addition, mesenchymal stem cells from different donors can vary in performance.

The cells that UB researchers modified show no signs of aging in culture, but otherwise appear to function as regular mesenchymal stem cells do – including by conferring therapeutic benefits in an animal study of heart disease. Despite their propensity to proliferate in the laboratory, MSC-Universal cells did not form tumors in animal testing.

“Our stem cell research is application-driven,” says Techung Lee, PhD, UB associate professor of biochemistry and biomedical engineering in the School of Medicine and Biomedical Sciences and the School of Engineering and Applied Sciences, who led the project. “If you want to make stem cell therapies feasible, affordable and reproducible, we know you have to overcome a few hurdles. Part of the problem in our health care industry is that you have a treatment, but it often costs too much. In the case of stem cell treatments, isolating stem cells is very expensive. The cells we have engineered grow continuously in the laboratory, which brings down the price of treatments.”

UB has applied for a patent to protect Lee’s discovery, and the university’s Office of Science, Technology Transfer and Economic Outreach (UB STOR) is discussing potential license agreements with companies interested in commercializing MSC-Universal.

Stem cells help regenerate or repair damaged tissues, primarily by releasing growth factors that encourage existing cells in the human body to function and grow.

Lee’s ongoing work indicates that this feature makes it feasible to repair tissue damage by injecting mesenchymal stem cells into skeletal muscle, a less invasive procedure than injecting the cells directly into an organ requiring repair. In a rodent model of heart failure, Lee and collaborators showed that intramuscular delivery of mesenchymal stem cells improved heart chamber function and reduced scar tissue formation.

UB STOR commercialization manager Michael Fowler believes MSC-Universal could be key to bringing new regenerative therapies to the market. The modified cells could provide health care professionals and pharmaceutical companies with an unlimited supply of stem cells for therapeutic purposes, Fowler says.

Lee says his research team has generated two lines of MSC-Universal cells: a human line and a porcine line. Using the engineering technique he and colleagues developed, scientists can generate an MSC-Universal line from any donor sample of mesenchymal stem cells, he says. “I imagine that if these cells become routinely used in the future, one can generate a line from each ethnic group for each gender for people to choose from,” Lee says.

The research was funded by the National Institutes of Health and New York State Stem Cell Science (NYSTEM).

BUFFALO, N.Y. -- Biomedical researchers at the University at Buffalo have engineered adult stem cells that scientists can grow continuously in culture, a discovery that could speed development of cost-effective treatments for diseases including heart disease, diabetes, immune disorders and neurodegenerative diseases. UB scientists created the new cell lines – named "MSC Universal" – by genetically altering mesenchymal stem cells, which are found in bone marrow and can differentiate into cell types including bone, cartilage, muscle, fat, and beta-pancreatic islet cells. The researchers say the breakthrough overcomes a frustrating barrier to progress in the field of regenerative medicine: The difficulty of growing adult stem cells for clinical applications. Because mesenchymal stem cells have a limited life span in laboratory cultures, scientists and doctors who use the cells in research and treatments must continuously obtain fresh samples from bone marrow donors, a process both expensive and time-consuming. In addition, mesenchymal stem cells from different donors can vary in performance. The cells that UB researchers modified show no signs of aging in culture, but otherwise appear to function as regular mesenchymal stem cells do – including by conferring therapeutic benefits in an animal study of heart disease. Despite their propensity to proliferate in the laboratory, MSC-Universal cells did not form tumors in animal testing. "Our stem cell research is application-driven," says Techung Lee, PhD, UB associate professor of biochemistry and biomedical engineering in the School of Medicine and Biomedical Sciences and the School of Engineering and Applied Sciences, who led the project. "If you want to make stem cell therapies feasible, affordable and reproducible, we know you have to overcome a few hurdles. Part of the problem in our health care industry is that you have a treatment, but it often costs too much. In the case of stem cell treatments, isolating stem cells is very expensive. The cells we have engineered grow continuously in the laboratory, which brings down the price of treatments." UB has applied for a patent to protect Lee's discovery, and the university's Office of Science, Technology Transfer and Economic Outreach (UB STOR) is discussing potential license agreements with companies interested in commercializing MSC-Universal. Stem cells help regenerate or repair damaged tissues, primarily by releasing growth factors that encourage existing cells in the human body to function and grow. Lee's ongoing work indicates that this feature makes it feasible to repair tissue damage by injecting mesenchymal stem cells into skeletal muscle, a less invasive procedure than injecting the cells directly into an organ requiring repair. In a rodent model of heart failure, Lee and collaborators showed that intramuscular delivery of mesenchymal stem cells improved heart chamber function and reduced scar tissue formation. UB STOR commercialization manager Michael Fowler believes MSC-Universal could be key to bringing new regenerative therapies to the market. The modified cells could provide health care professionals and pharmaceutical companies with an unlimited supply of stem cells for therapeutic purposes, Fowler says. Lee says his research team has generated two lines of MSC-Universal cells: a human line and a porcine line. Using the engineering technique he and colleagues developed, scientists can generate an MSC-Universal line from any donor sample of mesenchymal stem cells, he says. "I imagine that if these cells become routinely used in the future, one can generate a line from each ethnic group for each gender for people to choose from," Lee says.     The research was funded by the National Institutes of Health and New York State Stem Cell Science (NYSTEM).

In a report on a new paper called Cell Stem Cell from from Children’s Hospital Boston:  

“a new way to reprogram ordinary human cells into stem cells, using RNAs, appears safer and much more efficient than current methods – and can much more readily transform stem cells into specialized cells to treat disease.”

• Modified mRNAs can express reprogramming proteins and evade antiviral response
• Highly efficient derivation of human iPSCs without genomic integration
• RNA-derived iPSCs faithfully recapitulate the properties of human ESCs
• Efficient directed differentiation of iPSCs to differentiated myotubes

Derrick Rossi: Modified RNAs advance stem cell field

In a report on a new paper called Cell Stem Cell from from Children’s Hospital Boston:   “a new way to reprogram ordinary human cells into stem cells, using RNAs, appears safer and much more efficient than current methods – and can much more readily transform stem cells into specialized cells to treat disease.” Modified mRNAs can express reprogramming proteins and evade antiviral response Highly efficient derivation of human iPSCs without genomic integration RNA-derived iPSCs faithfully recapitulate the properties of human ESCs Efficient directed differentiation of iPSCs to differentiated myotubes Derrick Rossi: Modified RNAs advance stem cell field  

The use of stem cells for research and their possible application in the treatment of disease are hotly debated topics. In a special issue of Translational Research published this month an international group of medical experts presents an in-depth and balanced view of the rapidly evolving field of stem cell research and considers the potential of harnessing stem cells for therapy of human diseases including cardiovascular diseases, renal failure, neurologic disorders, gastrointestinal diseases, pulmonary diseases, neoplastic diseases, and type 1 diabetes mellitus.

Personalized cell therapies for treating and curing human diseases are the ultimate goal of most stem cell-based research. But apart from the scientific and technical challenges, there are serious ethical concerns, including issues of privacy, consent and withdrawal of consent for the use of unfertilized eggs and embryos.

“Publication of this special issue could not have been more timely, given the recent federal district court injunction against federal support for human embryonic stem cell research,” said Dr. Jeffrey Laurence, M.D., Professor of Medicine at Weill Cornell Medical College and Editor in Chief of Translational Research. “This court order stops all pending federal grants and contracts, as well as their peer review, suspending over 20 major research programs and over $50 million in federal funding for them,” he noted. As Dr. Francis Collins, NIH director, stated, “This decision has the potential to do serious damage to one of the most promising areas of biomedical research, just at the time when we were really gaining momentum.”

Through a series of authoritative articles authors highlight basic and clinical research using human embryonic and adult stem cells. Common themes include preclinical evidence supporting the potential therapeutic use of stem cells for acute and chronic diseases, the challenges in translating the preclinical work to clinical applications, as well as the results of several randomized clinical trials. Authors stress that considerable preclinical work is needed to test the potential of these approaches for translation to the clinical setting.

In considering the potential for clinical applications, some common challenges and questions persist. The issue focuses on critical questions such as whether the use of any stem cell population will increase the risk of cancer in the recipient and whether the goal of stem cell therapy is to deliver cells that can function as organ-specific cells.

Writing in a commentary on advances and challenges in translating stem cell therapies for clinical diseases, Michael A. Matthay, MD, Cardiovascular Research Institute, University of California San Francisco, notes that “the progress that has been achieved in the last 30 years in using allogeneic and autologous hematopoietic stem cells for the effective treatment of hematologic malignancies should serve as a model of how clinical applications may yet be achieved with embryonic stem cells, induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stem cells. Although several challenges exist in translating stem cell therapy to provide effective new treatments for acute and chronic human diseases, the potential for developing effective new cell-based therapies is high.”

http://www.sciencedaily.com/releases/2010/09/100910093156.htm

The use of stem cells for research and their possible application in the treatment of disease are hotly debated topics. In a special issue of Translational Research published this month an international group of medical experts presents an in-depth and balanced view of the rapidly evolving field of stem cell research and considers the potential of harnessing stem cells for therapy of human diseases including cardiovascular diseases, renal failure, neurologic disorders, gastrointestinal diseases, pulmonary diseases, neoplastic diseases, and type 1 diabetes mellitus. Personalized cell therapies for treating and curing human diseases are the ultimate goal of most stem cell-based research. But apart from the scientific and technical challenges, there are serious ethical concerns, including issues of privacy, consent and withdrawal of consent for the use of unfertilized eggs and embryos. "Publication of this special issue could not have been more timely, given the recent federal district court injunction against federal support for human embryonic stem cell research," said Dr. Jeffrey Laurence, M.D., Professor of Medicine at Weill Cornell Medical College and Editor in Chief of Translational Research. "This court order stops all pending federal grants and contracts, as well as their peer review, suspending over 20 major research programs and over $50 million in federal funding for them," he noted. As Dr. Francis Collins, NIH director, stated, "This decision has the potential to do serious damage to one of the most promising areas of biomedical research, just at the time when we were really gaining momentum." Through a series of authoritative articles authors highlight basic and clinical research using human embryonic and adult stem cells. Common themes include preclinical evidence supporting the potential therapeutic use of stem cells for acute and chronic diseases, the challenges in translating the preclinical work to clinical applications, as well as the results of several randomized clinical trials. Authors stress that considerable preclinical work is needed to test the potential of these approaches for translation to the clinical setting. In considering the potential for clinical applications, some common challenges and questions persist. The issue focuses on critical questions such as whether the use of any stem cell population will increase the risk of cancer in the recipient and whether the goal of stem cell therapy is to deliver cells that can function as organ-specific cells. Writing in a commentary on advances and challenges in translating stem cell therapies for clinical diseases, Michael A. Matthay, MD, Cardiovascular Research Institute, University of California San Francisco, notes that "the progress that has been achieved in the last 30 years in using allogeneic and autologous hematopoietic stem cells for the effective treatment of hematologic malignancies should serve as a model of how clinical applications may yet be achieved with embryonic stem cells, induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stem cells. Although several challenges exist in translating stem cell therapy to provide effective new treatments for acute and chronic human diseases, the potential for developing effective new cell-based therapies is high."   http://www.sciencedaily.com/releases/2010/09/100910093156.htm

Currently, once a donated organ has been harvested it only has a few hours on ice before it “expires.” Lengthening this time period would be an incredible breakthrough that would allow patients in a wider area to potentially receive a transplant and also it would reduce some of the insanity surrounding the time pressures of organ transplantation.
One proposed method of extending an organ’s shelf life is to alter the internal cell biology to allow cells to live longer at lower temperatures. The State University of New Jersey Rutgers-Camden just received a $385,419 grant from the NIH to study an enzyme system, AMP phosphatase, and how it can potentially create cold-tolerant Drosophila. The enzyme was originally identified in ice worms as the key enzyme that allows them to survive in glaciers. The researchers hope that if they are able to utilize this enzyme system to create a cold-tolerant fruit fly, then they would be able to apply that knowledge to donated organs.
Here’s more from the press release:

Not just the ice worm lives on ice; the Rutgers–Camden research team, which includes undergraduate and graduate students, observed how other organisms, like bacteria, fungi, and algae, also are breaking through their internal thermostats.
“Shain accomplished this switch in mono-cell organisms and now we are going further up into the evolutionary tree to a more complex species,” offers Yakoby, who joined the Rutgers­–Camden faculty last year after conducting postdoctoral research at Princeton University’s Lewis Sigler Institute for Integrative Genomics. “If we can get these human cells to survive on ice, we should expect organs to do the same. Organs are just a collection of cells.”

Another option would be to discover a way to actually freeze an organ without destroying the cells comprising it. Currently the very act of freezing an organ creates ice inside the cell, whose crystal structure tears them apart rendering them dead and useless. However, there is hope in the Wood Frog. When the wood frog is frozen its cells start to pump in glucose to lower the freezing temperature. Once the frog is frozen, the cells themselves are not. Once thawed out, the frogs resume their usual hopping lifestyle. Scientists have been frantically studying these frogs for years with the hope that they can unlock the secret to freezing and thawing organs. The fields of organ donation and cryogenics anxiously await results…

Currently, once a donated organ has been harvested it only has a few hours on ice before it “expires.” Lengthening this time period would be an incredible breakthrough that would allow patients in a wider area to potentially receive a transplant and also it would reduce some of the insanity surrounding the time pressures of organ transplantation. One proposed method of extending an organ’s shelf life is to alter the internal cell biology to allow cells to live longer at lower temperatures. The State University of New Jersey Rutgers-Camden just received a $385,419 grant from the NIH to study an enzyme system, AMP phosphatase, and how it can potentially create cold-tolerant Drosophila. The enzyme was originally identified in ice worms as the key enzyme that allows them to survive in glaciers. The researchers hope that if they are able to utilize this enzyme system to create a cold-tolerant fruit fly, then they would be able to apply that knowledge to donated organs. Here’s more from the press release: Not just the ice worm lives on ice; the Rutgers–Camden research team, which includes undergraduate and graduate students, observed how other organisms, like bacteria, fungi, and algae, also are breaking through their internal thermostats. “Shain accomplished this switch in mono-cell organisms and now we are going further up into the evolutionary tree to a more complex species,” offers Yakoby, who joined the Rutgers­–Camden faculty last year after conducting postdoctoral research at Princeton University’s Lewis Sigler Institute for Integrative Genomics. “If we can get these human cells to survive on ice, we should expect organs to do the same. Organs are just a collection of cells.” Another option would be to discover a way to actually freeze an organ without destroying the cells comprising it. Currently the very act of freezing an organ creates ice inside the cell, whose crystal structure tears them apart rendering them dead and useless. However, there is hope in the Wood Frog. When the wood frog is frozen its cells start to pump in glucose to lower the freezing temperature. Once the frog is frozen, the cells themselves are not. Once thawed out, the frogs resume their usual hopping lifestyle. Scientists have been frantically studying these frogs for years with the hope that they can unlock the secret to freezing and thawing organs. The fields of organ donation and cryogenics anxiously await results…     [youtube]http://www.youtube.com/watch?v=Fjr3A_kfspM[/youtube]