February 27, 2010 by

Coach’s fight a team effort

Sam Harrell is a well-known Ennis football coach and father of Texas Tech’s former quarterback Graham Harrell. Steve Betik has worked in construction for decades. Both of them suffer from multiple sclerosis. When they asked the Ennis chiropractor Dr. William Davis about using stem cells for their condition, his reaction was that it would be expensive, but if they wanted to go for it, he would help raise the needed funds. Both of them have registered for an experimental stem cell therapy offered in Central America by Cellmedicine. This is the same stem cell treatment that allowed Texas Fort Worth Police Sergeant Preston Walker, a patient with multiple sclerosis be able to
return to work after failing to respond to the medication given by his neurologist.

Treatment for multiple sclerosis generally addresses symptoms, but when conventional approaches stop inducing responses, there are very little options left. One area of active investigation has been stem cell therapy. Although very new, a small three-year study by the Northwestern University School of Medicine concluded last year that stem cell transplants from the patients’ own bodies might help control or even reverse symptoms.

Unfortunately, FDA approval of such methods, even if documented in larger research, is years away. Specifically, three phases of clinical trials have to be conducted. Phase I involves testing of safety. Phase II clinical trials
test whether there is a therapeutic effect, however these are “unblinded” in that the patients know that they are receiving an experimental treatment, thus the possibility exists of placebo effect. Phase III clinical trials are performed at multiple hospitals in a “double blinded” manner so that neither the doctor, nor patient knows whether they are receiving the treatment or the placebo. At present stem cell therapy for multiple sclerosis has only reached
Phase I/II clinical trials.

Companies such as www.cellmedicine.com offer stem cell therapy based on the same science and medical practices used in the United States. To date over 200 patients with multiple sclerosis have been treated by Cellmedicine, however they openly state that the procedure is experimental. This did not deter Sam Harrell and Steve Betik.They are scheduled to fly together in June to the Cellmedicine clinic in Central America, where Harrell is expected to remain two weeks; Betik, a month.

In order to raise funds to support their treatment, the Ennis football boosters club, in conjunction with the town’s chamber of commerce, is hosting a dinner and auction April 10. Davis and others hope that any excess funds they raise through the Foundation for Hope will be applied to an annual fundraiser for anyone with special needs.

“We’re like babies crawling,” Davis said of their efforts. “Who knows what the future will hold?”

Patients interested in learning more about Cellmedicine can go to the website www.cellmedicine.com or view videos at www.youtube.com/cellmedicine

Filed Under: Multiple Sclerosis, News, Stem Cell Therapy Tagged With: , , ,
February 26, 2010 by

Adult Stem Cells Healing Hearts

Adult stem cells are being more and more used in patients
to achieve effects.  In the treatment of patients with heart failure, Dr. David
Prentice, discussed two studies in which adult stem cells appear to have some
benefit. 

The first study was the result of a Brazil-Florida joint
effort in which it was discovered that adult stem cells injected directly into
the heart could relieve angina. These data are not all that surprising given
that the first use of stem cells for heart failure involved a similar injection
procedure in Japan more than a decade ago.   Stem cell administration for
cardiac conditions has been performed in numerous clinical trials, here is a
link to a video on a previously published Phase III study in patients who
previously had a heart attack

http://www.youtube.com/watch?v=flv0RmzPyLU

In the current study eight patients were received the stem
cell treatment and according to the principle investigator Dr. Nelson Americo
Hossne, Jr, all of the patients treated exhibited some degree of improvement. 
The study suggested that the patients improved through stimulation of production
of new blood vessels.  Furthermore, the authors believed that the cells and the
procedure used to administer them are safe and effective. 

Dr. Hossne stated "For our patients, angina symptom
relief began as early as three months post-procedure with continuing improvement
through the twelfth month and sustained improvement past 18 months. Symptom
relief improved in all patients, suggesting that the effect is sustained, not
transitory."

The second study that Dr. Prentice discussed is from a
Chinese group in which the protein apelin was demonstrated to have an effect on
the ability of cardiac regenerative mechanisms.  In the study, 20 heart failure
patients were treated with their own bone marrow, 20 received placebo, and 20
healthy patients were compared for control.  All twenty of the heart failure
patients treated with adult stem cells showed significant improvement in cardiac
function within 21 days of treatment, while the standard medication patients
showed no improvement. The patients who received stem cells demonstrated a
significant increase in levels of apelin, which correlated with the recovery of
cardiac function.

Dr. Amit Patel, a world-recognized stem cell pioneer,
professor at University of Utah School of Medicine and an Editor of the journal
in which the papers were published stated: "Both studies demonstrate a
possible mechanistic approach in a clinical trial. These important findings
further enhance the understanding of the use of bone marrow derived cell therapy
for the treatment of cardiovascular disease."

Filed Under: Adult Stem Cells, Heart Disease, News, Stem Cell Research Tagged With: , , , , ,
February 26, 2010 by

Fat May Serve a Purpose in Stem Cell Research

Scientist Dr. Joseph Wu at the Stanford University School
of Medicine has recently published a new and improved method to generate stem
cells "artificially".  For almost a decade there has been substantial
controversy regarding the use of embryonic stem cells, with the debate becoming
socially and politically focused as opposed to based on science: one camp
believing that embryonic stem cell research must be supported at all costs, the
other camp believing that adult stem cells can do anything that embryonic stem
cells can do, so there should be no research performed in this area.  This
debate became somewhat irrelevant when the Japanese group of Yamanaka discovered
a method of "dedifferentiating" adult cells into cells that appear at a
molecular and functional level similar to embryonic stem cells.  These
"artificial" stem cells, called inducible pluripotent stem cells (iPS) have
several unique properties:  They don’t need to be extracted from embryos; they
can be made from the same patient that they will be used on; and the methods of
manufacturing can be relatively standardized. 

To date these cells have been demonstrated to be capable of
generating not only every tissue in the body tested, but they also can improve
disease conditions in animal models ranging from heart attacks, to liver
failure, to bone marrow reconstitution.  Unfortunately the biggest problem with
iPS cells is that they are difficult to generate.  In order to understand this,
it is important to first mention how the cells are made.  Adult cells have the
same DNA blueprint as embryonic stem cells.  However in adult cells certain
portions of the DNA are not used to make proteins.  So in liver cells the DNA
that encodes for proteins found in the skin is "silenced" or "blocked" from
making proteins by various chemical modifications that occur as a cell is
maturing.  Embryonic stem cells are considered "blank slate" cells because the
DNA is capable of expressing every protein found in the body.  In order to make
an adult stem cell "younger" so as to resemble an embryonic stem cell, it is
necessary to somehow reprogram the DNA in order to allow it to express every
gene.  So how would one go about doing this? There is one biological condition
in which adult cells take the phenotype of younger cells.  This is in cancer. 
This is the reason why some types of cancer start expressing proteins that other
cells normally produce.  For example certain liver cancers can produce insulin,
even though liver cells do not produce insulin.  The concept that certain cancer
genes can evoke a "rejuvenation" of adult cells was used by Yamanaka as a
starting point.  His group found that if you insert the oncogene c-myc, together
with the stem cell genes Nanog, Oct-4, and SOX-2 skin cells will start to look
like embryonic stem cells.  If these cells are placed on top of feeder cells
then they can be expanded and used as a substitute for embryonic stem cells.

The current problem with wide-scale use of this approach is
that insertion of the various genes into the cells requires the use of viruses
that literally infect the cells with the foreign genes.  Not only can the
viruses cause cancer, but also the genes administered can cause cancer because
they are oncogenes.  The other hurdle is that generation of iPS cells is a very
inefficient process.  It takes approximately 2-3 months to generate stable
cells, and these cells are usually generated from approximately 1 out of
100-300,000 starting cells.  We previously discussed advances that allowed for
uses of non-hazardous means of inserting genes into cells to make iPS

https://www.celllmedicine.com/thomson-safer-ips.asp , in this current article
another approach was described to increase efficacy.

Scientists used as starting population not skin cells,
which are considered substantially differentiated, but instead used fat derived
stem cells.  This type of stem cell is very much a mesenchymal stem cell

http://www.youtube.com/watch?v=qJN2RyBj78I and possesses ability to
transform into different tissues already.  Thus by starting with a cell that is
already more "immature", scientists have been able to increase the rate of iPS
generation, as well as, alleviate the need for the oncogene c-myc.

Other approaches being investigated on increasing
generation of iPS cells include use of chemicals that affect the DNA structure
such as valproic acid.  This is interesting because simple administration of
valproic acid on bone marrow stem cells has been demonstrated to increase their
"stemness"

http://www.youtube.com/watch?v=3Hc4LCUOSiA .

Although we are still far from the day when
individual-specific stem cells will be available for widespread use, we are
getting closer to this dream at a very fast pace.

Filed Under: Adult Stem Cells, Embryonic Stem Cells, News, Stem Cell Research Tagged With: , , , , ,
February 24, 2010 by

Stem Cells for HIV?

HIV infection causes its devastating effects on patients by
destruction of the CD4 T helper cell and macrophage component of the immune
system.  Entry of the virus into these cells occurs via binding to the molecules
CD4 and CCR5.  Interestingly a group of patients who appear to be resistant to
HIV infection have a mutation in the CCR5 protein.  Studies conducted on these
patients have demonstrated that the mutation in CCR5 results in resistance to
infection, while other components of the immune system of these patients are
intact.  Thus one possible method of treating HIV would be if somehow one could
induce the CCR5 mutation that is protective from HIV into the immune cells of
patients.  It is very difficult to selectively mutate established immune cells,
however, one possibility would be if one could induce such a mutation in stem
cells, and then administer the stem cells to the patient so that they
"differentiate" into immune cells.

Scientists from the Department of Microbiology, Immunology
and Molecular Genetics, at the David Geffen School of Medicine, University of
California at Los Angeles have started figuring methods of doing this. 
Specifically, a new technology called "RNA Interference" was used to selectively
block expression of the CCR5 gene on stem cells.  RNA interference is a process
that is normally used by mammalian cells to protect themselves against viruses. 
Specifically, RNA is found only as a single strand in mammalian cells.  Double
stranded RNA is found only in viruses.  When a mammalian cell recognizes double
stranded RNA it believes that a viral infection is occurring and two processes
are triggered.  The first is gene-nonspecific.  Regardless of what is coded in
the double stranded RNA, the cell starts to produce the protein interferon,
which blocks other cells from being infected, as well, the cell alters various
metabolic activities and enters a quiescent state.  The second process is
gene-specific, in that the cell will destroy any other RNA that resembles what
is encoded in the double strand.  While the first effect is useful for
inhibition of viral infections, it is non-specific and causes general toxicity
when administered at high enough levels to people or animals in order to elicit
an effect.  Thus a Nobel Prize was awarded in 2006 to Fire and Mello when they
discovered that by administering pieces of double stranded RNA shorter than 21
nucleotides, the selective gene-silencing effect could be induced in absence of
the non-selective "interferon effect".

In their recent paper, Liang et al used RNA interference to
block expression of the CCR5 gene on stem cells that are capable of giving rise
to both CD4 T cells, as well as macrophages.  They demonstrated that
gene-blockade was passed on to the progeny of the stem cell, and that the newly
generated cells were resistant to HIV infection in vitro.

In contrast to using stem cells for hematopoietic
transplantation, in which depletion of the original recipient cells is required,
the use of genetically engineered stem cells for treatment of HIV would not
require such myeloablation since the HIV infection will naturally be killing the
non-manipulated cells.

Filed Under: HIV, News, Stem Cell Research Tagged With: , , , , ,
February 21, 2010 by

Hope Through Stem Cell Therapy

Mary Posta suffers from multiple sclerosis, a debilitating
disease that progressively degenerates the nervous system of its victims through
stripping away the insulator proteins surrounding the nerves called myelin.

In January of this year Mary Posta completed raising funds
to be treated by Cellmedicine in Central America using stem cells and returned
from treatment feeling "really good".  Specifically, after a month spent at
Cellmedicine, she stated "I can walk and talk better, and there are other
things." She adds "My memory seems to be better. I’m moving faster on thinking
and talking, and I have a lot more energy. I used to have to take sleeping pills
but have not had to start taking them again."

The stem cell therapy comprises of an intensive four-week
program of stem-cell and physical therapies.  The stem cells used are from adult
sources and therefore are not subjected to the ethical controversy associated
with other types of stem cells such as fetal or embryonic stem cells.

Cellmedicine has previously published results of the first
three multiple sclerosis patients in a peer reviewed medical journal which can
be found at this link

http://www.translational-medicine.com/content/pdf/1479-5876-7-29.pdf

The approach used involves administration of the cells
purified from the fat of the patients.  These cells contain two types of stem
cells, one called mesenchymal and the other called hematopoietic.  Additionally,
cells extracted from fat include alternatively activated macrophages and T
regulatory cells.  At a theoretical level these cells may be mediating their
effects as follows: 

Mesenchymal stem cells are known to inhibit multiple
sclerosis when administered in animal models of the disease, as seen in this
video

http://www.youtube.com/watch?v=D2RIuCc5h0A .  The video discusses one
mechanism by which mesenchymal stem cells achieve this effect, particularly
through induction of an enzyme called indolamine 2,3 deoxygenase, which is
responsible for shutting down autoreactive T cells.  Since multiple sclerosis is
a disease in which T cells are mediating destruction of the myelin sheath,
suppression of autoreactive T cells is theoretically beneficial.  Additionally,
mesenchymal stem cells are known to produce various growth factors that increase
ability of the body’s own cells to repair themselves.  Furthermore, some studies
have suggested that mesenchymal stem cells themselves are capable of
differentiating into oligodendrocytes and Schwann cells, which produce myelin,
as well as into brand new nervous system tissue. 

Hematopoietic stem cells are conventionally known as
the cells that are responsible for the therapeutic effect of bone marrow
transplantation.  That is, these are the cells that produce all the blood cells
in the body.  More recent studies have shown that hematopoietic stem cells, such
as CD34 positive cells,  are capable of producing growth factors such as IGF-1,
these are capable of protecting various cells in the body from premature cell
death.  Additionally, there are some studies that suggest CD34 cells are capable
of regenerating injured nervous system tissue.

Alternatively activated macrophages comprise a
subset of the immune system cell classically known as the "big eater".  While
conventional macrophages are involved in protecting the body from disease by
eating pathogens, as well as producing inflammatory stimuli, alternatively
activated macrophages are involved in healing of damaged tissue.  It is known
that alternatively activated macrophages generate substances such as
interleukin-10 that shut down ongoing immunological/inflammatory reactions, as
well as assist in tissue healing.

T regulatory cells resemble the "anti-matter" of T
cells.  The body has two parallel universes of T cells.  The conventional T
cells are responsible for attacking everything that does not belong to the
body.  That is, conventional T cells recognize and kill bacteria, viruses, and
other pathogens.  On the other hand, T regulatory cells recognize everything
that "belongs" to the body.  For example, there are T regulatory cells in the
body that recognize myelin.  The difference between T regulatory cells and
conventional T cells is that T regulatory cells do not "kill" but instead
prevent what is being recognized by conventional T cells from being killed.  In
other words the T regulatory cells serve as a backup mechanism for the immune
system so that in situations such as multiple sclerosis, where the conventional
T cells are attacking something that they should not be attacking, the T
regulatory cells try to inhibit that attack.  Unfortunately in multiple
sclerosis, by the time the disease is clinically detected, the T regulatory
cells are not exerting their effects for reasons some known and some unknown. 
Adipose tissue contains high numbers of T regulatory cells, which are more
potent than T regulatory cells found from other tissues in the body.  This is
explained in this video, which discusses a publication from Harvard Medical
School
http://www.youtube.com/watch?v=rEJfGu29Rg8.

Given the potent combination of stem cells, and other
therapeutic cells, found in fat tissue, it is interesting that the company
Vet-Stem has already commercialized the procedure of using fat-derived cells for
treatment of companion animals.  Here is a video discussing some of Vet-Stem’s
technologies
http://www.youtube.com/watch?v=hEkSJo3CmPc .

Use of fat stem cells in patients with multiple sclerosis
has been previously reported in numerous other media venues:

CBS News:

http://www.youtube.com/user/cellmedicine#p/u/24/wIcUaKZWOSE

Fox 4 News:
http://www.youtube.com/user/cellmedicine#p/u/25/1j1F57olCdI

Texas Channel 8 News:
http://www.youtube.com/user/cellmedicine#p/u/21/r_mOKM5__00

CBS 4 News:
http://www.youtube.com/user/cellmedicine#p/u/19/mxd6t3izxtw

Filed Under: Multiple Sclerosis, News, Stem Cell Therapy Tagged With: , , ,
December 31, 2009 by

Scientists Develop Technique to Determine Ethnic Origin of Stem Cell Lines

(HealthDay News) The majority of embryonic stem cell research is being conducted on lines that have been established years ago from frozen in vitro fertilization embryos. Many times the ethnic origin of these cells is not known, or when it is, specific issues as to country of origin versus actual ethnicity are not clear.
Scientists at the Scripps Research Institute in La Jolla, California have reported what they believe to be a potential solution to this puzzle. The team, lead by Dr. Jeanne Loring, published a paper in the January 2010 edition of the journal Nature Methods in which they reveal a molecular technique that could be useful for answering this question.

"Ethnic origin is a critical piece of information that should come with every cell line," said Dr. Loring. "Everyone who works with stem cells should be doing this kind of analysis."

Dr. Loring was referring to numerous situations in which different ethnicities have different biological responses to drugs or medical treatments. Although in the majority of cases these differences are subtle, situations such as metabolism of specific drugs or organ rejection can have terrible consequences if ethnicity is not taken into consideration. In the study, Dr. Loring’s team analyzed a variety of human embryonic stem cell lines that are being used in laboratory research internationally. Of these cell lines, the majority originated from donors of Caucasian and East Asian descend, with no representation from Africa.

In order to address this problem, brand new stem cells were generated using the inducible pluripotent stem cell (iPS) method from a donor of West African Yoruba origin. This cell line was the first pluripotent cell line to have the genetic make-up of a person from this ethnic group. The iPS technology essentially allows for the generation of cells that resemble both functionally, and molecularly embryonic stem cells without the need for using fertilized eggs. Scientists have previously reported that introduction of certain genes into skin cells, or other types of adult cells, can be used to "de-differentiate" adult cells into a phenotype that resembles embryonic stem cells. By being able to take adult cells and generated cells that resemble embryonic stem cells, scientists such as Dr. Loring have made pluripotent stem cell lines not only from humans of different ethnicities, but also individuals with various diseases, as well as animals at risk of extinction.

"Knowing that a big push in the future is using these lines in the clinic and in drug development, there’s a need to have an ethnically diverse population of cells," added Louise Laurent, M.D., Ph.D., assistant professor at the University of California, San Diego (UCSD) and research associate at Scripps Research, who is first author of the paper with Caroline Nievergelt, Ph.D., also an assistant professor at UCSD.

The current research was based on a previously described molecular biology technology in which specific gene signatures are correlated with ancestry of individuals. On such project, the International HapMap Project, was published in the journal Nature in 2003. This effort linked single-letter alterations in the genetic code — known as single nucleotide polymorphisms, or SNPs — with people of known ethnic origins. This data provided a way to identify the ethnic heritage of a donor of any cell.
"There’s not a lot of value in making a new pluripotent stem cell line now unless it has something new to offer," said Loring. "I think that increasing ethnicity and genetic diversity is an important reason for generating new lines."

"Essentially this publication represents a shift in our thinking about stem cells. Initially the major issue in stem cell research has been how to generate different tissues, now scientists are beginning to take it for granted that tissue generation is occurring and the next issues of transplantation, matching, and scale-up are being considered".

Filed Under: News, Stem Cells, Uncategorized Tagged With:
December 30, 2009 by

Stem Cells Might Reverse Heart Damage From Chemo

One of the great findings of regenerative medicine was that organs previously believed to be incapable of healing themselves actually contain stem cells that in response to injury cause some degree of healing. The problem being that these "endogenous healing mechanisms" are usually too small to mediate effects that are visible at the clinical level. For example, the brain was considered to have very limited ability to heal itself after damage. Recent studies that have allowed for observation of brain cells after experimental strokes have led to the discovery of brain stem cells in the dendate gyrus and subventricular zones of the brain, stem cells that start to multiple after a stroke. Interestingly, various hormones such as human chonrionic gonadotropin, are capable of stimulating brain stem cell multiplication. This is currently being used in clinical trials for stroke by the company Stem Cell Therapeutics.

In the area of heart failure, it was also believed that once cardiac tissue is damaged, the only repair process that the body performs is production of scar tissue, which is pathological to the patient. While this scar tissue is found in the majority of the injured area, molecular studies have revealed the existence of cardiac specific stem cells, which start to multiply after injury and serve to repair, albeit in small amounts, the infarct area.

One way to augment endogenous repair processes is to administer stem cells from the bone marrow, which are known to produce various growth factors that assist the tissue-specific stem cell in mediating its activity. Another way is to physically extract the tissue specific stem cells, expand them outside of the body and reimplant them into the damaged area.

In a recent publication in the journal Circulation, Piero Anversa, M.D., director, Center for Regenerative Medicine, Departments of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women’s Hospital, Boston and Roberto Bolli, M.D., chief, cardiology, and director, Institute of Molecular Cardiology, University of Louisville, Kentucky, describe the use of cardiac specific stem cells in treatment of animals whose hearts of been damaged by the chemotherapeutic drug doxorubicin.
Doxorubicin is a chemotherapeutic drug that is mainly used in the treatment of breast, ovarian, lung, and thyroid cancers, as well as for neuroblastoma, lymphoma and leukemia. One of the main limiting factors to increasing the dose of doxorubicin to levels that can lead to tumor eradication is that it causes damage to the heart muscle, the myocardium.

In the published study, the investigators expanded the cardiac specific stem cells from rats, gave the rats high doses of doxorubicin and in some rats injected back cardiac specific stem cells, whereas other rats received control cells. The rats that received the cardiac specific stem cells had both preservation of cardiac function, and also regeneration of the damaged heart tissue. This is an important finding since the type of damage that doxorubicin does to the heart is different from other types of heart damage that have been studies, such as the damage that occurs after a heart attack. These data seem to suggest that stem cell therapy may be useful in a variety of injury situations.

"Theoretically, patients could be rescued using their own stem cells," said study author Dr. Piero Anversa, director of the Center for Regenerative Medicine at Brigham and Women’s Hospital in Boston. Dr. Aversa is one of the original discoverers of the cardiac specific stem cell when he published experiments in dogs demonstrating multiplication of cells in the myocardium that seem to have ability to generate new tissue after damage (Linke et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71).

"A Phase 1 clinical trial using a similar procedure in people is already under way", said Dr. Roberto Bolli, chief of cardiology and director of the Institute of Molecular Cardiology at the University of Louisville in Kentucky, who is heading the trial. The FDA has approved a Phase I clinical trial using cardiac specific stem cells in 30 patients who have congestive heart failure due to disseminated atherosclerosis. "In the trial, participants’ cardiac tissue will be harvested, the stem cells isolated and then expanded in vitro from about 500 cells to 1 million cells over several weeks", Bolli explained. "Several months after the patient has undergone bypass surgery, the stem cells will be re-injected." A similar clinical trial is being performed at Cedars Sinai in Los Angeles.

While the problems of tissue extraction (which is performed by an invasive procedure requiring biopsy of heart tissue) and cost of expansion are still formidable hurdles to widespread implementation, it is believed that the clinical evidence of a therapeutic response will open the door to other avenues of expanding tissue specific stem cells, such as administration of growth factors that can accomplish this without need for cell extraction outside of the body.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , ,
December 28, 2009 by

Stem Cell as Anti-Aging “Medicine”

Medistem Inc issued a press release describing a collaborative publication between the University of California San Diego, Indiana University, University of Utah, the Dove Clinic for Integrative Medicine, Biotheryx, NovoMedix, The Bio-Communications Research Institute, The Center for Improvement of Human Functioning International and Aidan Products, discussing the contribution of circulating endothelial cells to prevention of aging. The publication also provided data showing that healthy volunteers who have been administered the food supplement Stem-Kine had a doubling of circulating endothelial progenitor cells.

The paper "Circulating endothelial progenitor cells: a new approach to anti-aging medicine?" is freely accessible. "Numerous experiments and clinical trials have been published describing the importance of these repair cells that the body possesses to heal internal organs," stated Dr. Doru Alexandrescu from Georgetown Dermatology, a co-author of the publication. "However, to our knowledge, this is the first comprehensive blueprint in the peer-reviewed literature of how this knowledge may be applied to the question of aging."

The paper summarizes publications describing correlations between decline of circulating endothelial cells and aging/deterioration of several organ systems. The main hypothesis of the publication is that the bone marrow generates a basal number of circulating endothelial cells that serve to continually regenerate the cells that line the blood vessels. Many diseases that are prevalent in aging such as Alzheimer’s are associated with dysfunction of the blood vessel’s ability to respond to various stimuli. This dysfunction is believed to be caused by diminished numbers of circulating endothelial progenitor cells.

Other conditions such as peripheral artery disease are also associated with reduction in this stem cell population, however, when agents are given that increase the numbers of these cells, the degree of atherosclerosis-mediated pathology is decreased. This was demonstrated in a study that administered the drug GM-CSF, which causes an increase in circulating endothelial progenitor cells in a manner similar to Stem-Kine. Unfortunately, drugs currently on the market that have this ability are very expensive and possess the possibility of numerous side effects. The Stem-Kine food supplement is sold as a neutraceutical and is made of natural ingredients that have already been in the food supply.

Another interesting point made by the paper was that the body modulates the number of circulating endothelial progenitor cells based on need. In stroke, the number of circulating endothelial progenitor cells markedly increases in response to the brain damage. Patients in which a higher increase is observed are noted to have a higher chance of recovery. Therapeutic interventions that contain endothelial progenitor cells such as administration of bone marrow cells after a heart attack, are believed to work, at least in part, through providing a cellular basis for creation of new blood vessels, a process called angiogenesis.

Patients with inflammatory conditions ranging from chronic heart failure, to type 2 diabetes, to Crohn’s disease are noted to have a reduction in these cells. The reduction seems to be mediated by the inflammatory signal TNF-alpha. Studies reviewed in the paper describe how administration of antibodies to TNF-alpha in patients with inflammatory conditions results in a restoration of circulating endothelial progenitor cells.

In addition to the possible use of Stem-Kine for restoration/maintenance of circulating endothelial progenitor cells, the publication discusses the possibility of using such cells from sources outside of the body, for example cord blood. Although it was previously thought that cord blood can be used only after strict HLA matching, recent work supports the idea that for regenerative medicine uses, in which prior destruction of the recipient immune system is not required, cord blood may be used without immune suppression or strict tissue matching. This is discussed in the following paper: Cord blood in regenerative medicine: do we need immune
suppression?.

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
December 23, 2009 by

Adenosine inhibits chemotaxis and induces hepatocyte-specific genes in bone marrow mesenchymal stem cells

Bone marrow cells contain several populations that are useful for regenerating injured/aged tissue. These cells include hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and some argue, progenitor cells left over from embryonic periods that are still capable of differentiating into numerous injured tissue. It has been known for some time that bone marrow cells are capable of treating liver failure both in vitro and in early clinical trials, as can be seen on this video: Stem Cell Therapy for Liver Failure. Other types of stem cells useful for treatment of liver failure, such as cord blood stem cells, may be seen on this video: Cord Blood and Bone Marrow Stem Cells for Liver Failure.

One of the major questions with adult stem cell therapy is how do the stem cells go to where they are needed? Some people have made the argument that stem cells administered intravenously do not cause systemic effect because the majority get stuck in the lung and liver. Although cell sequestration is an issue, numerous studies have demonstrated therapeutic effects after intravenous administration of stem cells. Perhaps the most well-known stem cell homing molecule is stromal derived factor (SDF-1), which is made by injured and/or hypoxic tissue and causes stem cell mobilization and migration through activation of the CXCR4 receptor. The SDF-1/CXCR4 axis has been found in numerous conditions of tissue injury such as: stroke, heart attack, acoustic injured ear, liver failure, and post-transplant reconstitution of bone marrow. To understand how this “chemokine” works, the following video will describe it as relevant to stem cell repopulation post-irradiation: Homing of Stem Cells to Target Tissue

In a study published today scientists examined another signal made by injured tissue in order to assess whether it may act like SDF-1 and “call in” stem cells. The signal chosen was the amino acid adenosine, which is released from injured/necrotic cells. They found that adenosine did not by itself induce chemotaxis of mesenchymal stem cells (MSC) but dramatically inhibited MSC chemotaxis in response to the chemoattractant hepatocyte growth factor (HGF). Inhibition of HGF-induced chemotaxis by adenosine requires the A2a receptor and is mediated via up-regulation of the cyclic adenosine monophosphate (AMP)/protein kinase A pathway. Additionally, the investigators found that adenosine induces the expression of some key endodermal and hepatocyte-specific genes in mouse and human MSCs in vitro.

The ability of adenosine to modulate migration/differentiation processes implies that numerous paracrine/autocrine interactions are occurring during tissue injury. It will be critical to identify how to manipulate such factors to obtain maximal therapeutic responses.

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
December 21, 2009 by

Athersys May Get Up To $111M from Pfizer In Stem-Cell Deal

Classically Big Pharma has been focused on development small molecule drugs that can be readily made en masse, and whose chemistry is well understood. Biologics such as antibodies have also been gaining popularity, albeit at a slower rate. Stem cells are more difficult than biologics in terms of manufacturing, however, despite this, there has been some increasing interest by Big Pharma in this area in the last couple years. For example, in June 24th, 2008 Pfizer provided Series A funding for EyeCyte, a San Diego company dedicated to generating cell based treatments for diabetic retinopathy. A mega-deal between Osiris Therapeutics and Genzyme worth over a billion dollars was signed on Nov 4, 2008 for the rest of world rights for the mesenchymal stem cell products Prochymal and Chondrogen.

On August 7, 2009 Opexa and Novartis signed a $50 million deal involving a $4 million upfront payment for a pre-clinical stem cell technology. More recently, Pfizer signed a deal worth $111 million with Athersys involving development of the MultiStem product in the area of inflammatory bowel disease.

"Pfizer is committed to the development of new medicines that have the potential to fundamentally improve the quality of clinical care in areas of need. We are delighted to work with Athersys to develop MultiStem for inflammatory bowel disease," said Dr. Ruth McKernan, Head of Pfizer Regenerative Medicine. "This is an innovative new area and our collaboration with Athersys represents a cornerstone of Pfizer’s stem cell and regenerative medicine strategy."

Athersys is a clinical stage biopharmaceutical company that is developing both stem cell and non-stem cell based drugs. Its Regenerative medicine pipeline includes the use of MultiStem for acute myocardial infarction, bone marrow transplant support, and ischemic stroke. Its small molecule drug pipeline contains novel pharmaceuticals to treat indications such as obesity, as well as certain conditions that affect cognition, attention and wakefulness.

The MultiStem product is a mesenchymal-like stem cell that is capable of becoming numerous types of tissues including heart, brain, muscle, and blood vessels. As found for mesenchymal stem cells derived from other sources, the MultiStem product does not require matching with the recipient. This allows for cells to be used as "universal donor" or a "one size fits all" approach.

"We have been systematically evaluating potential partnering opportunities in multiple areas, and we believe that Pfizer represents the ideal partner for this program," said Dr. Gil Van Bokkelen, Chairman and Chief Executive Officer at Athersys. "Their longstanding global leadership in development and commercialization of new medicines, focus on best-in-class therapies, and their growing commitment to regenerative medicine provide a great foundation for working together."

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