Irvine, Calif., March 10, 2010 – A clinical research trial of a new treatment to
restore brain cells damaged by stroke has passed an important safety stage,
according to the UC Irvine neurologist who led the effort.
Dr. Steven C. Cramer said patients showed no ill effects after the sequential
administration of growth factors encouraging the creation of neurons in
stroke-damaged areas of the brain. All new drug treatments must pass this safety
stage before doctors can study their effectiveness in subsequent studies.
Results of the phase IIa trial appear on the Web site of Stroke, a journal of
the American Heart Association.
Within two days of suffering ischemic stroke, patients were put on a nine-day
treatment course, starting with three once-daily injections of beta-hCG, a
hormone that triggers the growth of neural stem cells. They then received three
once-daily injections of erythropoietin, a hormone that directs these neural
stem cells to become neurons.
Cramer, associate professor of neurology at UCI, said this combination of growth
factors had been shown in animal studies to engender neuron creation leading to
the recovery of a range of movement.
In the human safety study, he teamed with physicians from UC Irvine Medical
Center; Hoag Memorial Hospital Presbyterian in Newport Beach, Calif.; and the
University of Calgary in Canada. They administered the treatment to 15 patients.
No safety concerns were noted, and a majority of treated patients had minimal or
no disability after three months.
A phase IIb clinical trial is now under way to compare the stroke therapy with
The study is supported by Stem Cell Therapeutics a Canadian biotechnology
company that conceived of an approach using this specific sequence of growth
factors and the National Center for Research Resources.
Dr. Centeno is offering stem cell therapies for orthopedic damage with remarkable results. Is this the future of stem cells in the US?
The FDA has yet to approve stem cell therapies for general use in medicine, but that hasn’t stopped doctors in Colorado from providing them anyway. Chris Centeno and John Schultz have boldly formed Regenerative Sciences Inc. in Broomfield, Colorado. RSI provides its patients with the Regenexx procedure, an adult stem cell transplant that uses your own cells (autologous) to treat joint injuries and bone damage. There’s no surgery needed. A needle extracts bone marrow, RSI isolates the stem cells and cultures them in your own blood, and then these cells are injected into the area where they are needed. They’ve treated 348+ patients with 800+ injections and show no signs of slowing down. According to RSI’s own surveys, 89% of their knee patients showed marked improvement, as did 75% of their hip patients! Within months some patients can walk or run in ways they haven’t been able to in years. We’ve seen these kinds of results from stem cell treatments before, but only in horses and dogs. That’s because human stem cell therapies like this one aren’t approved by the FDA. How can Centeno and Schultz flaunt the lack of federal approval? They claim that Regenexx is solely used as a part of their medical practice, only within the state of Colorado, and as such is no more regulated by the FDA than it would be by the FAA or the Department of Motor Vehicles. For hundreds of patients, he and his team are providing a remarkable hope. They’ve brought lab-cultured medical stem cell therapies to the US. Finally.
Stem cells have been a focal point for hype and hope for years now. Besides healing horses and dogs, they have promising effects on diabetes, corneal blindness, even HIV. It’s pretty clear that they’re also the future of organ transplants. Just the news of a stem cell related development or patent will cause a biotech company’s stocks to soar. The FDA, which regulates all interstate drug sales and related clinical trials is not trying to keep Americans from these “miraculous” cures, it’s simply trying to make sure they are safe first. Apparently, that’s taking too long. Medical tourism agencies are starting to cater to those seeking stem cell treatments. Whether or not they are ready for widespread medical use, stem cell therapies are in high demand, not just in the US but around the world. It’s no longer a question of when we will have access to these treatments, it’s a question of how.
A severely damaged knee healed to a remarkable degree. Must be stem cells. RSI is offering adult stem cell therapies in the US. That’s an important first, but what will happen without FDA approval?
Patient’s interested in the Regenexx procedure face what seems to be a fairly standard experience for autologous stem cell transplants. It takes 20-40 minutes to extract the cells from hip bone marrow with limited anesthesia, and blood is also taken. Over a month RSI’s lab will isolate mesenchymal (multipotent) adult stem cells and multiply them until they have 1 to 10 million. Typically, a patient will receive an injection into the treated area once a month for three months. Positive results are sometimes seen quickly (in 1 to 3 months) but will hopefully develop within 6 to 9 months. Importantly, there’s no down time as a result of the procedure. Patients can leave the clinic and go home after each injection. A round of Regenexx (extraction, cultivation, and 3 injections) costs $7000-$8500. Those who produce exceptional numbers of stem cells can use subsequent injections (even in other parts of the body) for around $3500. Most insurances will not cover the treatment.
The fact that RSI isolates and cultures (multiplies) the cells is a big difference from other clinics that offer stem cell therapies. That process allows the lab to create enough mesenchymal stem cells to really have an effect on the area in which they are injected. Many clinics around the world will take blood, marrow, or tissue and then spin out the stem cells in a centrifuge, injecting them back in on the same day. That style of therapy could possibly be effective, but it is far less likely than with a dose of millions of multipotent stem cells. There are several doctors around the US that will provide such ’single-visit’ stem cell therapies, but RSI is offers the lab cultured mesenchymal therapy in the US. Dr. Centeno has confirmed that he’s the only one, that he knows of, openly using this particular procedure in the US.
In the past, many have been very skeptical of stem cell treatment centers in other countries. First, let’s look at the success RSI is selling. Autologous transplants are offered in the hands, hips, knees, shoulders, back (non-spinal cord injury), ankles, and bone fractures. For each of these procedures you can find many ardent and exceptionally encouraging patient testimonials on their website, or their YouTube channel, along with a flood of supportive media.
Overall, RSI is claiming around 80% patient satisfaction according to its own surveys. That’s incredible, especially when you see some of their patients walking and running again on joints that have experienced years of chronic damage. It also seems Centeno and Schultz have the documented evidence to back up the claims for Regenexx’s success. RSI provides case studies for each of its treatments as well as published scientific research. According to my conversation with Centeno, RSI is currently working on a comprehensive statistical analysis of their more popular treatments so they can publish quantitative results in a peer review journal. In other words, they’ll soon publish the hard numbers – X% of patients feel Y% better Z months after the procedure.
Importantly, RSI seems to be upfront with patients about the limits of their own technique. The website FAQ clearly states that not all results will be like the testimonials, and they even have a dedicated page explaining that stem cell therapies won’t work for everyone. Furthermore, RSI has published the largest study of risks and complications associated with stem cell treatments yet produced in the US (N=227). That paper demonstrates the very low harm associated with stem cell therapies – much lower than the alternative surgery(published in Current Stem Cell Research & Therapy). Centeno claims that if we’re really worried that autologous stem cell therapies are going to hurt someone, this paper pretty much shows they won’t.
The concerns most people have with RSI are not medical, they’re political. Many applaud Centeno and Schultz for supplying the public with the cutting edge technology they demand, but worry about the manner in which it has been accomplished. Skirting FDA approval for a technique through the arguments they use opens the gate to a host of problems. If RSI can provide Regenexx because it is a doctor’s procedure not involved in interstate commerce, does that mean someone else can do the same for another treatment? What are the limits of such procedures? How does a patient know if a doctor’s therapy is safe, or effective, if it hasn’t undergone peer review and government inspection?
Doctors and surgeons are developing new procedures all the time. Surgeons will often create new devices for their own use in surgery, doctors routinely try out new dosing regimes, or therapies on their patients. This is part of the medical profession.
Still, it’s possible that even though RSI is doing what many other doctors routinely do (develop a new therapy for use in their own practice) that the federal government could try to bring them to court. The FDA seems to have taken the stance that all stem cells (whether used autologously or not) are drugs. As such, they would need FDA approval, and would likely only be developed by large pharmaceutical companies.
According to Lee Buckler of Cell Therapy Blog, Centeno’s already received a warning letter from the FDA. Centeno clarified that this is actually an “untitled letter” which has no bearing on regulation. He pointed me to this explanation on untitled letters. RSI has faced concerns from the New York Department of Health, and went so far as to pursue a provisional license, even though they are no where near NY state. Clearly RSI is hoping to avoid bureaucratic problems or at least be very prepared for them if they do arise. Perhaps with enough positive results they can avoid legal battles and even convince insurance companies to cover Regenexx.
Hopefully so. Just look as these results. They’re pretty damn amazing. If you accept the success rates, and the possibilities for long term healing…many people need this.
Centeno says he is working with others to provide the framework through which many more patients could receive mesenchymal stem cell therapies. He’s on the board of the International Cell Medicine Society (ICMS) which is working to track stem cell therapy patients through a registry, as well as certify stem cell clinics for practice. Through conferences and seminars, doctors are trained in IVF to work in fertility clinics. Centeno explained to me that a similar practice could instruct and track physicians interested in providing lab cultured autologous stem cell therapies. In other words, the technique used by RSI could become a regularly seen procedure in specialty clinics across the country. That may mean more patients could have access to stem cells soon.
FDA approval is slow, but it’s coming. Athersys has a patent for a stem cell derived drug, other companies have therapies in clinical trials. Those treatments will be here some day. In the meantime, RSI is filling in the gap. Their work may even catch on as a trend. If largely successful, insurance companies may pay for it and the federal government may end up grandfathering Regenexx in at some point. It could happen. What’s certain is that the public demand for stem cell therapies is real, growing, and seemingly justified. When that sort of pressure for a technology exists nobody can keep it down.
There is no conclusive understanding of what the long term effects of stem cells treatments will be. We do not know if a stem cell treatment will be effective 5-10 years after it is administered, and we know of no large study that has conclusively reviewed patients for cancer, or any long term side effect 5-10 years after a stem cell injection. Part of what ICMS is trying to do (reviewing clinics, tracking patients results over the long term) may yield a better understanding in the future.
[Sources: Regenerative Sciences Inc, ABC 7 News in Denver, Lee Buckler , RSI Blog, Current Stem Cell Research & Therapy]
HOUSTON — (March 5, 2010); Components of the blood or hematopoietic
system derive from stem cell subtypes rather than one single stem cell that
gives rise to all the different kinds of blood cells equally, said scientists
from Baylor College of Medicine (www.bcm.edu) in a report that appears in the
current issue of the journal Cell Stem Cell (www.cell.com/cell-stem-cell/)
“While previous reports in journals have hinted at the possibility of stem cell
subtypes, this study represents the clearest data to show that is true,” said
Dr. Margaret Goodell, director of the Stem Cells and Regenerative Medicine
(STaR) Center (www.bcm.edu/star/) at BCM. “From a scientific point of view, it’s
making us re-evaluate the view of the stem cells that come from adults. It
challenges the dogma that there is one type of stem cell.”
She and the report’s first author, Dr. Grant A. Challen, a postdoctoral
associate in the Center for Cell and Gene Therapy (www.bcm.edu/genetherapy/) at
BCM, said that the stem cell subtypes they identified meet the strictest
To accomplish this, Challen, Goodell and their colleagues used a special dye
technique to discriminate the different hematopoietic stem cell subtypes –
myeloid, which have a preference for giving rise to red blood cells, macrophages
(non-specific immune cells that engulf foreign bodies) and similar cells; and
lymphoid, which similarly preferentially give rise to the body’s immune system
By transplanting single stem cells into individual mice, Challen was able to
confirm that these subtypes exist and act as the researchers had thought. The
subtypes also maintain a stable population of the stem cells over time, another
characteristic of these progenitor cells.
“We cannot rule out that there is a single progenitor cell to both sub-types,”
said Goodell. “We don’t know where to look for it. Maybe it does not exist or
maybe it exists only when the bone marrow begins to be made but does not persist
The finding has implications for treatment.
“People have been looking for purer and purer stem cell types,” Goodell said.
“In doing that, they may not be getting all the stem cell types they need. Maybe
in the clinic, it is better to have less pure types.”
“You may need a spectrum of stem cells to create a complete blood system,” said
In bone marrow or peripheral blood stem cell transplants for cancers or blood
disorders, doctors often wipe out a patient’s own bone marrow and replace it
with stem cells that can repopulate the bone marrow. Scientists are constantly
improving that system.
As animals age, their proportions of stem cell subtypes change, Challen said.
“The myeloid cells have a slower rate of baseline turnover and a higher rate of
self renewal. They persist over time, such that the myeloid-biased stem cells
become more prevalent with time. This may have implications for how different
types of cancers become more prevalent with age.”
The two types react differently to the presence of transforming growth factor
beta, Challen said. One type increases and the other decreases.
Challen said it is also important to remember the big question.”Does this
translate to humans as well? Some markers may be different, but I think it
Goodell holds the Vivian Smith Chair of Regenerative Medicine at BCM.
NEW YORK (March 4, 2010) — In a leap toward making stem cell therapy widely
available, researchers at the Ansary Stem Cell Institute at Weill Cornell
Medical College have discovered that endothelial cells, the most basic building
blocks of the vascular system, produce growth factors that can grow copious
amounts of adult stem cells and their progeny over the course of weeks. Until
now, adult stem cell cultures would die within four or five days despite best
efforts to grow them.
“This is groundbreaking research with potential application for regeneration of
organs and inhibition of cancer cell growth,” said Dr. Antonio M. Gotto Jr., the
Stephen and Suzanne Weiss Dean of Weill Cornell Medical College and Provost for
Medical Affairs of Cornell University. “We are indebted to Shahla and Hushang
Ansary for founding this Institute and to the Starr Foundation Tri-Institutional
Stem Cell Initiative for ongoing support.”
This new finding sets forth the innovative concept that blood vessels are not
just passive conduits for delivery of oxygen and nutrients, but are also
programmed to maintain and proliferate stem cells and their mature forms in
adult organs. Using a novel approach to harness the potential of endothelial
cells by “co-culturing” them with stem cells, the researchers discovered the
means to manufacture an unlimited supply of blood-related stem cells that may
eventually ensure that anyone who needs a bone marrow transplant can get one.
The vascular-cell model established in this study could also be used to grow
abundant functional stem cells from other organs such as the brain, heart, skin
and lungs. An article detailing these findings appears in the March 5 issue of
the journal Cell Stem Cell.
In adult organs, there are few naturally occurring stem cells, so using them for
organ regeneration is impractical. Until now, strategies to expand cultures of
adult stem cells, which invariably used animal-based growth factors, serum, and
genetically manipulated feeder cells, have only been marginally successful. This
study, which employs endothelial cells to propagate stem cells without added
growth factors and serum, will likely revolutionize the use of adult stem cells
for organ regeneration, as well as decipher the complex physiology of the adult
“This study will have a major impact on the treatment of any blood-related
disorder that requires a stem cell transplant,” says the study’s senior author,
Dr. Shahin Rafii, the Arthur B. Belfer Professor in Genetic Medicine,
co-director of the Ansary Stem Cell Institute and a Howard Hughes Medical
Institute Investigator, at Weill Cornell Medical College. Currently, stem cells
derived from bone marrow or umbilical cord blood are used to treat patients who
require bone marrow transplants. Most stem cell transplants are successful, but
because of the shortage of genetically matched bone marrow and umbilical cord
blood cells, many patients cannot benefit from the procedure.
“Over the last few decades, substantial funding has been spent to develop
platforms to expand adult stem cell cultures, but these efforts have never been
able to coax an authentic adult stem cell to self-renew beyond a few days,”
continues Dr. Rafii. “Most stem cells, even in the presence of multiple growth
factors, serum, and support from generic non-endothelial stromal cells, die
after a few days. Now, employing our endothelial stem cell co-cultures, we can
propagate bona fide adult stem cells in the absence of external factors and
serum beyond 21 days with an expansion index of more than 400-fold.”
If this vascular-based stem cell expansion strategy continues to be validated,
physicians could use any source of hematopoietic (blood-producing) stem cells,
propagate them exponentially, and bank the cells for transplantation into
In a true first, the study demonstrates how this novel vascular cell platform or
“vascular niche” can self-renew adult hematopoietic stem cells for weeks, both
in vitro and in vivo, by co-culturing them on a bed of endothelial cells. The
researchers chose endothelial cells because they are in close contact with blood
stem cells, and previous work from Dr. Rafii’s lab had demonstrated that
endothelial cells produce novel stem-cell-active growth factors. However,
maintenance of the endothelial cells is cumbersome and if they are not “fed”
specific substances, such as growth factors known as “angiogenic factors,” they
immediately die. To get around this problem, the researchers genetically
engineered the endothelial cells to stay in a long-term survival state by
inserting a recently discovered gene cloned from adenoviruses, which does not
promote oncogenic transformation of the human cells. This earlier discovery,
using a single gene to put endothelial cells into a long-lasting “suspended
animation” state without harming their ability to produce blood vessels, was
also discovered in Dr. Rafii’s lab and published in the journal Proceedings of
National Academy Sciences in 2008.
Endothelial Cells Could Generate Stem Cells and Their Differentiated Progeny
In this study, the researchers also discovered that endothelial cells not only
could expand stem cells, but also instruct stem cells to generate mature
differentiated progeny that could form immune cells, platelets, and red and
white blood cells, all of which constitute functioning blood.
“We are the first group to demonstrate that endothelial cells elaborate a
repertoire of stem-cell-active growth factors that not only stimulate stem cell
expansion but also orchestrate differentiation of these stem cells into their
mature progeny,” says Dr. Jason Butler, a senior investigator at Weill Cornell
Medical College and first author of the study. “For example, we have found that
expression of specific stem-cell-active factors, namely Notch-ligands, by the
endothelial cells lining the wall of working blood vessels promote proliferation
of the blood-forming stem cells. Inhibition of these specific factors on the
endothelial cells resulted in the failure of the regeneration of the
blood-forming stem cells. These findings suggest that endothelial cells
directly, through expression of stem-cell-active cytokines, promote stem cell
Further describing this innovative concept, in a high-impact article published
in the January 2010 issue of Nature Reviews Cancer, Drs. Rafii and Butler, and
Dr. Hideki Kobayashi, who is also a co-author of the current study, have
elaborated on specific endothelial cell-produced growth factors that promote the
growth of tumor cells besides stem cells.
Development of the vascular-cell technology that supports long-lasting growth of
stem cells will also allow scientists to generate abundant sources of functional
and malignant stem cells for genetic and basic studies. This study has also
resolved a long-standing controversy in which several groups had claimed that
bone-forming cells (osteoblasts) exclusively support the expansion of
blood-forming stem cells. “However, using a highly sophisticated molecular
imaging approach, we show that regenerating blood-forming stem cells in the bone
marrow are in intimate contact with the blood vessels, indicating that
endothelial cells are the predominant regulator of stem cell repopulation in the
adult bone marrow,” states Dr. Daniel Nolan, a senior scientist in Dr. Rafii’s
lab and a co-author of the new study.
One other important concern addressed in this study was whether forced expansion
of the stem cells over a long period of time would induce cancerous mutations in
the stem cells. However, the authors of this study show that, even after one
year, there was no indication of tumor formation, such as leukemias, when the
expanded stem cells were transplanted back into mice. This suggests that the
endothelial cells provide a milieu that proliferates stem cells without creating
Dr. Rosenwaks says, “Generation of endothelial cells derived from diseased
embryonic stem cells that are being propagated in our Derivation Unit will open
up new avenues of research to molecularly eavesdrop on the communication between
vascular cells and stem cells. This innovative line of investigation to
determine how normal and abnormal human vascular cells induce the formation of
organs during development of embryos and how dysfunction of endothelial cells
results in developmental defects will lay the foundation for novel platforms
for therapeutic organ regeneration.”
Dr. Rafii sees even more opportunities. “Identification of as yet unrecognized
growth factors produced by human embryonic cell-derived endothelium and adult
endothelial cells that support stem cell expansion and differentiation will
establish a new arena in stem cell biology. We will be able to selectively
activate endothelial cells not only to induce organ regeneration, but also to
inhibit specifically the production of endothelial cell-derived factors in order
to block the growth of tumors. Our findings are the first steps toward such
goals and they highlight the potential of vascular cells for generating
sufficient stem cells for therapeutic organ regeneration, tumor targeting, and
gene therapy applications,” concludes Dr. Rafii.
For more information, visit www.med.cornell.edu.
March 2, 2010 – Houston – A heart patient’s own skin cells soon could be used to
repair damaged cardiac tissue thanks to pioneering stem cell research of the
University of Houston’s newest biomedical scientist, Robert Schwartz.
His new technique for reprogramming human skin cells puts him at the forefront
of a revolution in medicine that could one day lead to treatments for
Alzheimer’s, diabetes, muscular dystrophy and many other diseases.
Schwartz brings his ground-breaking research to UH as the Cullen Distinguished
Professor of Biology and Biochemistry and head of UH’s new Center for Gene
Regulation and Molecular Therapeutics. He also is affiliated with the Texas
Heart Institute at St. Luke’s Episcopal Hospital in the Texas Medical Center,
where he is director of stem cell engineering.
“Professor Schwartz’s work will save lives, and his decision to pursue this
pioneering research at UH is a big leap forward on our way to Tier-One status,”
said John Bear, dean of the UH College of Natural Sciences and Mathematics.
“Together with the many other outstanding scientists we’ve assembled here,
Schwartz will help make this university a major player in medical research.”
Schwartz devised a method for turning ordinary human skin cells into heart
cells. The cells developed are similar to embryonic stem cells and ultimately
can be made into early-stage heart cells derived from a patient’s own skin.
These then could be implanted and grown into fully developed beating heart
cells, reversing the damage caused by previous heart attacks. These new cells
would replace the damaged cardiac tissue that weakens the heart’s ability to
pump, develops into scar tissue and causes arrhythmias. Early clinical trials
using these reprogrammed cells on actual heart patients could begin within one
or two years.
Although Schwartz is not the first scientist to turn adult cells into such stem
cells, his improved method could pave the way for breakthroughs in other
diseases. Schwartz’s method requires fewer steps and yields more stem cells.
Armed with an effective way to make induced stem cells from a patient’s own
skin, scientists can then begin the work of growing all kinds of human cells.
For example, new brain cells could treat Alzheimer’s patients or those with
severe brain trauma, or a diabetic could get new insulin-producing cells in the
pancreas. Generating new kidney, lung or liver tissue is also possible, with
scientists even being able to one day grow an entirely new heart or other organ
from these reprogrammed cells. Additionally, Schwartz and his team are working
on turning induced stem cells into skeletal muscle cells to treat muscular
“We’re trying to advance science in ways folks never even dreamed about,”
Schwartz said. “The idea of having your own bag of stem cells that you can
carry through life and use for tissue regeneration is at the very cutting edge
This latest biomedical hire is a major step in the UH Health Initiative, an
effort aimed at having the university become a world-class center for medical
research. Creating new cross-disciplinary academic and health-related research
opportunities for faculty and students is crucial to this initiative, as are
collaborations with other Texas Medical Center member institutions. One of its
top goals is to increase the amount of sponsored research expenditures awarded
to UH, which is a key factor in attaining Tier-One status.
“Dr. Schwartz will expand UH’s expertise in promising new areas of scientific
discovery to alleviate human disease. By recruiting premier scientists like
Schwartz, UH is fast becoming a major player in the regional biomedical research
community,” said Kathryn Peek, assistant vice president of University Health
Initiatives at UH.
Schwartz has decades of experience at the Texas Medical Center. Before coming
to UH, he was director of the Institute of Biosciences and Technology, a
research component of the Texas A&M Health Science Center. He also was a
longtime tenured professor at Baylor College of Medicine and co-directed the
school’s Center for Cardiovascular Development. The new research center
Schwartz heads at UH will be housed in state-of-the-art laboratory facilities at
the university’s Science and Engineering Research Center.
What attracted him to UH was the commitment of administrators and faculty to
making the university a premier center for biomedical research. His hiring
comes just a year after the arrival of Jan-Åke Gustafsson, a world-renowned
scientist and cancer researcher. They join other leading UH faculty, ranging
from biochemists to computer scientists and mathematicians, who are deeply
involved in cutting-edge medical research.