April 8, 2010 by

Cord Blood Stem Cell Therapy for Cerebral Palsy in Clinical Trial

Cerebral palsy is characterized by hypoxia/reperfusion
induced damaged to the brain in the perinatal period. It is manifested in four main types: a)
Spastic, which occurs in 70-80% of cases and is associated with damage to the
corticospinal tract or the motor cortex; b) Ataxic, occurs in 10%, is
associated with damage to the cerebrum, and causes deficiencies in walks, hearing
and speech; c) Athetoid/dyskinetic is caused by injury to the to the
extrapyramidal motor system and/or pyramidal tract and to the basal ganglia, it
occurs in approximately 20% of cases. Cerebral
palsy is a non-progressive disorder in which recovery does not occur and
treatments revolve around addressing symptomology. The possibility of stem cell therapy for
cerebral palsy was proposed by Cellmedicine several years ago and is discussed
in this video http://www.youtube.com/watch?v=egRxgUXDN4Y
.

One type of stem cell that has been used for cerebral palsy
comes from the cord blood. Usually cord
blood stem cells are used for treatment of hematological (blood) disorders such
as leukemias or genetic metabolic conditions. Cellmedicine proposed the use of cord blood for conditions such as
cerebral palsy
http://www.translational-medicine.com/content/pdf/1479-5876-5-8.pdf
because of: a) its superior growth factor producing ability to other types of
adult stem cells; b) the possibility of using cord blood with minimal matching;
and c) the ability of cord blood stem cells to directly differentiate into
other types of cells relevant to cerebral palsy such as neurons and glial
cells.

In order to test validity of the possibility that cord blood
may be useful for such a condition, the developmental cycle that occurs with
drugs has to be applied. That is,
firstly animal data needs to support the possibility of efficacy, as well as
the safety of the intervention. Secondly, pilot human studies are needed to determine if it is feasible
to administer the cells in patients with the particular disease without
possibility of adverse effects. Thirdly,
formal clinical trials need to be initiated. These usually begin with Phase I trials that assess safety and maximally
tolerated dose, Phase II trials that assess efficacy in a non-blinded manner,
and Phase III trials that seek efficacy in a
double-blind placebo-controlled manner.

Groups like Cellmedicine have been involved in treatment of
patients with cord blood. Additionally,
Dr. Joanne Kurtzburg from Duke has been using the patient’s own cord blood in
treatment of patients with cerebral palsy http://www.youtube.com/watch?v=xLmY7Ps65wQ. Both
of these treatments were considered part of the "practice of medicine" and may
be comparable to "pilot investigations" in that safety data was generated and
the medical procedure for physically administering the cells was
developed.

Today a group at the Medical College of Georgia announced
initiation of Phase I/II Placebo-Controlled, Observer-Blinded, Crossover Study
to Evaluate the Safety and Effectiveness of a Single, Autologous, Cord Blood
Stem Cell Infusion for the Treatment of Cerebral Palsy in Children.

The trial involves 40 patients between ages 2-12 who are
seizure-free and have clinical evidence
of a non-progressive motor disability due to brain dysfunction. The subjects recruited
will not have the ability to sit independently by one year of age or the
ability to walk by 18 months of age.

Patients will be
divided into 2 groups, with the first group receiving red-cell depleted, mononuclear
cell enriched cord blood unit prepared for infusion (treatment) and the second
being administered saline combined with the inert stem cell administration
solution lacking stem cells. The
observer and patient will not know who is receiving cells from which
group.

The main observation endpoints of the trial will be safety of autologous (patient’s own)
cord blood infusion in children with cerebral palsy by repeated follow-up over
one year with clinical and laboratory evaluations. The secondary endpoint will
be determination of whether a beneficial effect has occurred in the
recipients. This will be measured using
a patient questionnaire and standardized Gross Motor Function Measure
evaluation with effects anticipated to be seen within 3-4 months.

Conceptually this study is a very safe one because it is the
patient’s own cord blood stem cells that are being used. This however could also be a negative
issue. There is some evidence that when
stem cells from another individual (allogeneic) are used, it is the reaction
between the recipient and donor that gives rise to production of numerous
growth factors. Since this current
treatment is only using the patient’s own cells, it may be similar to simply
adding your own blood back into you. The
animal studies previously performed involved using human cord blood cells in
mice lacking part of the immune system. Additionally they used much higher concentration of cord blood cells per
kilogram of body weight. Regardless, it
is very important to state that this study lays the groundwork for translation
of numerous stem cell approaches that have previously been used for patient
treatment outside of the US, for US approval.

Parents of patients interested in trial participation should
contact James E Carroll, M.D. the Principle Investigator of the study at 706-721-3371 jcarroll@mcg.edu

Filed Under: Adult Stem Cells, Cerebral Palsy, News, Stem Cell Research Tagged With: , , , ,
March 5, 2010 by

Stem Cell Treatment for Heart Attacks: Timing is Everything

Skeletal myoblasts are a type of muscle-specific stem cell
that have been used previously in several clinical trials, particularly for
heart failure and post-heart attack patients.  Advantages of this type of stem
cell include the fact that they are from adult sources (no risk of cancer), they
are already committed to becoming muscle cells, and they can easily be grown in
the laboratory.  Disadvantages include the possibility of arrhythmias, as well
as lack of efficacy in several systems. Additionally, unlike mesenchymal stem
cells, which can be used as "universal donors" because of their
anti-inflammatory effects, skeletal myoblasts have to either be used from the
same patient (autologous), or co-administered with immune suppression to prevent
their rejection.

In a recent publication (O’Blenes et al. Engraftment is
optimal when myoblasts are transplanted early: the role of hepatocyte growth
factor. Ann Thorac Surg. 2010 Mar;89(3):829-35) Canadian researchers at
Dalhousie University sought to determine whether an optimum time exists for
myoblast administration after cardiac injury. 

Using rats, the scientists cut off circulation to the
coronary artery to mimic a heart attack by ligation using microsurgery. 
Myoblasts where implanted at the time of ligation or 5 weeks after the infarct. 
Much higher engraftment of the cells was observed in animals that received the
cells immediately after the infarct.  Additionally, the hearts that received
myoblasts earlier seemed to have less damage.  This prompted the scientists to
ask the question; "why would delayed administration result in less homing and
retention?"

Previously we at Cellmedicine discussed the biological
observation that after a heart attack the injured heart muscle generates
chemicals that attract the body’s own stem cells.  One of these chemicals is
VEGF, which was discussed in this video

http://www.youtube.com/watch?v=NqEggEYilh0. Another chemical made by injured
heart tissue is hepatocyte growth factor (HGF).  Both of these proteins are made
when cells "sense" reduced oxygen, as well as various alterations in their
environment.  In the current study it was found that levels of HGF are
substantially elevated after the infarct and subsequently diminish by the 5th
week.  The investigators found that HGF stimulated proliferation and activity of
the myoblasts, and therefore believed that the decline in HGF may be one of the
reasons for the decreased efficacy with time. 

This could be a possible explanation for their results,
however, numerous factors may also be important to consider.  For example, it is
known in various situations of injury that as scar tissue forms, components of
the scar tissue inhibit regeneration.  Stem cells such as bone marrow
mesenchymal cells contain matrix metalloproteases that actively can "dig
through" scar tissue and support regeneration.  Myoblasts do not express such
enzymes, and additionally do not have the same homing ability to injured tissue.

The study would have substantially made more of a strong
case for the importance of HGF in stem cell activity if they used blocking
antibodies or knock-out mice specific for this gene.  Such a study would have
conclusively demonstrated the importance of HGF in this situation by
demonstrating less stem cell homing in its absence. 

One interesting point that is made is the possibility of
administering HGF into the myocardium of patients so as to enhance stem cell
homing.  Indeed, some companies such as Bioheart are already using such an
approach, see link

http://www.bioheartinc.com/prod-myocellsdf1.html.

Filed Under: Adult Stem Cells, Heart Disease, News, Stem Cell Research Tagged With: , , , ,
March 3, 2010 by

Contract’s end means changes for stem cell scene

In 2005 WiCell, a nonprofit organization affiliated with
the University of Wisconsin was charged with creating and maintaining a national
embryonic stem cell bank supported by the Federal Government.  At that time the
21 embryonic stem cell lines that were approved by former president George W.
Bush’s administration were made available for researchers.  The importance of
this stem cell bank was two-fold: firstly to provide a consistent and
reproducible source of cells for experimentation that scientists across the
nation could use and compare results; and secondly to reduce costs of accessing
the stem cells.  Usually they would cost tens of thousands of dollars, however
thanks to WiCell they were made available for approximately $500 for academic
use. 

Since creation of the bank, the nature of embryonic stem
cell research has markedly changed.  In particular, the July 2009 order issued
by President Barack Obama to allow federal funding for stem cells other than the
original 21 cell lines has stimulated expansion into the cells available for
research.  Last week the contract that formed WiCell’s National Stem Cell Bank
expired and a new bank called Wisconsin International Stem Cell (WISC) Bank was
formed.  This bank offers not only the original 21 cell lines but also several
newer types of embryonic stem cells, as well as induced pluripotent stem cells (iPS). 

This new type of stem cell has attracted much publicity
because it is derived from non-embryonic sources but seems to have identical
characteristics to embryonic stem cells.  Particularly, iPS cells can become all
tissues of the body, in the same way that embryonic stem cells can, and
additionally, these cells are capable of forming tumors when injected in mice. 
Tumor formation in animals is a defining characteristic of embryonic stem
cells. 

Janet Kelly a representative from WiCell said under WISC
Bank, lines now cost $1,000.

"Without a national bank or provision for the NIH to fund
any type of stem cell bank, it will be challenging for researchers to obtain
stem cells that are thoroughly tested and meet high standards for quality
assurance in a reliable and efficient manner," Kelly said in an e-mail to the
Badger Herald. "Researchers already are confused about how to obtain the newly
approved cell lines and many of the originators of these lines do not want to
operate a distribution service."

Despite the fact that the WISC bank is not federally
funded, Erik Forsberg, executive director of WiCell believes that business will
flourish.  "In some ways you could view it as a setback, but the reputation is
so well-established I think in the long run it won’t have a big effect,"
Forsberg said. "It certainly helps to have the connections with the U.S.
government or the national stem cell bank, but because we have stem cell lines
all over the world, I think the reputation will remain."

For more information on iPS cells, you can watch the video
at

http://www.youtube.com/watch?v=_RLlUdJLy74

Filed Under: News, Stem Cells, Uncategorized Tagged With: , , , ,
February 28, 2010 by

Ahmedabad-based institutes get patent to use stem cells in kidney transplant

According to an article IndianExpress.com, an international
patent has been issued to the G R Doshi K M Mehta Institute of Kidney Diseases
and Research Centre (IKDRC) and Dr HL Trivedi Institute of Transplantation
Sciences (ITS) from Ahmedabad, Indian for utilization of stem cells in treatment
of patients having undergone kidney transplantation.  Given that we could not
find a patent number written in the article, as well as the fact that
"International Patents" do not exist, we presume the authors meant a provisional
patent having international priority under Paris Convention, or a Patent
Cooperation Treaty (PCT) application. 

The subject matter discussed is the use of stem cells to
circumvent the need for immune suppression during transplantation.  While immune
suppressants such as cyclosporine, rapamycin, and FK-506 have saved many lives
by making transplantation possible, they have numerous side effects associated
with their long-term use.  These include increased risk of cancer, higher number
of bacterial/viral infections, and possibility of kidney failure.  The work
discussed in the article uses the ability of stem cells to "immune modulate" and
therefore inhibit rejection.  A video describing stem cell mediated immune
modulation may be seen at this link

http://www.youtube.com/watch?v=ECi2uBSSQg8.  

Dr Aruna Vanikar, Head of Pathology, Lab Medicine,
Transfusion Services and Immuno hematology department, IKDRC-ITS, who according
to the article recently received the patent, stated, "We have been working on
the use of stem cells since 1998. The study involved several phases. When a
patient undergoes kidney transplant, he/she might face difficulties, including
complete rejection. To suppress that, several drugs are used…Sometimes, the body
also reacts to high dosage of drugs. With this patent, patients will not have
any such complications. The stem cells would comprise mesenchymal cells
generated from the donors’ fat, and haematopoetic stem cells taken from donors’
bone marrow and blood. These cells are infused in the recipients’ liver, as it
is considered the most tolerogenic organ of the body."

While the article did not provide technical details, we
found on

www.pubmed.com some of Dr. Vanikar’s work.  A recent publication: Effect of
co-transplantation of mesenchymal stem cells and hematopoietic stem cells as
compared to hematopoietic stem cell transplantation alone in renal
transplantation to achieve donor hypo-responsiveness. In the journal Jan 19th
edition of the International Urology and Nephrology Journal described the
reduction of immune suppressant dosage by administration of bone marrow and fat
derived stem cells.  Another paper from the same group described the reduction
of immune suppressant dose by a similar stem cell protocol, termed the
"Ahmedabad tolerance induction protocol".  It will be interesting to see if
these early clinical results can be translated into Phase III placebo controlled
trials.  Commenting on the "tolerance induction protocol" Dr Aruna Vanikar said:
"With modification in Ahmedabad tolerance induction protocols for
transplantation without conventional immunosuppression, the results are
rewarding. Secondly, the incidences of acute and chronic rejection and
recurrence of basic disease have decreased."

Filed Under: Kidney and Lung, News, Stem Cell Research 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 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: , , , ,
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