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 8, 2010 by

Stem cell therapy shows early promise: Celgene

Crohn’s disease is a favorite amongst mesenchymal stem cell
development companies. This may be because on the one hand, this type of stem
cell possesses anti-inflammatory properties, and on the other hand it has the
potential to regenerate injured tissue. Additionally since the quality of life
of patients with advanced Crohn’s Disease is so poor, and current treatments are
generally ineffective at addressing the root cause, that new treatments usually
receive much support from regulatory agencies. Crohn’s disease is characterized
as a chronic inflammatory condition of the gastrointestinal tract. It is
believed to affects almost one million people in the United States.

Today Celgene announced Phase I safety data on its
placental mesenchymal stem cell product PDA-001 in a trial of 12 patients. The
patients suffered from active moderate-to-severe Crohn’s and were unresponsive
to at least one prior conventional therapy. The treatment with stem cells
comprised two infusions of PDA-001 one week apart. The patients were divided
into 2 groups with 6 patients being administered a lower number of cells and six
a higher number.

According to Celgene, "The study met its primary safety
goal and demonstrated encouraging signs of clinical benefit, including clinical
remission among four patients in the low dose group". Interestingly the company
declined to speculate on why the lower number of cells elicited superior
benefit. As an interesting aside, the company Osiris Therapeutic conducted a
similar clinical trial in Crohn’s Disease using stem cells derived not from
placenta but from bone marrow sources.

The CEO of Celgene’s Cellular Therapeutics unit, Dr. Robert
Hariri stated "We are encouraged that in these patients with Crohn’s disease our
unique, placenta-derived therapies show signs of clinical benefit," he continued
"We will continue to aggressively pursue the clinical development of this and
other cellular therapies derived from what we see as one of the richest sources
of uniquely functional and versatile cells."

The company anticipates moving into Phase II clinical
trials not only in the area of Crohn’s but also in other degenerative
indications.

It is an interesting point that the cells were administered
intravenously. There are some groups that believe stem cells only work if
administered locally. This study suggests that the need for local injection may
not be as important as some others believe. Additionally, since companies like
Cellmedicine use various mesenchymal stem cell sources, the current results
provide US-based scientific evidence supporting at least the rationale for this
approach.

Filed Under: Adult Stem Cells, Clinical Trials, Crohn's Disease, News, Stem Cell Research Tagged With: , ,
March 5, 2010 by

Histostem Works With Korean Government Agency to Provide Cord Blood Storage for Multicultural Families

The US company Amstem through subsidiary signed a
partnership agreement with the Songpa-Gu Office of the Seoul Metropolitan
Government, to provide umbilical cord blood banking to multicultural families
for up to 15 years.  Cord blood is currently used for treatment of patients with
blood disorders such as leukemias as an alternative to bone marrow. 
Unfortunately many patients do not have suitable donors, this is especially true
in patients of various ethnicities.  The current program is designed to overcome
this problem.

The president of AmStem International, Inc., David Stark
 stated  "This provides AmStem and Histostem with another ‘badge of validity’
with government health agencies around the world. A diverse genetic catalogue of
autologous, HLA-typed stem cell resources such as cord blood is in extremely
high demand right now — not only by individual families, but by
government-sponsored scientists and other researchers worldwide. This is exactly
the kind of collaborative, networking opportunity that AmStem hopes to expand in
North America and Europe."

In recent years the use of cord blood for diseases not
associated with blood has been increasing.  For example, the Cord Blood Bank
Viacell has patents on the use of cord blood for treatment of Duchenne Muscular
Dystrophy (Kraus et al. US patent #7452529 – Treatment of muscular dystrophy
with cord blood cells).  The Cellmedicine.com group has collaborated with
the US company Medistem at publishing use of cord blood together with other
cells for treatment of a patient with Duchenne Muscular Dystrophy that resulted
in functional improvement (Ichim et al. Mesenchymal stem cells as anti-inflammatories:
implications for treatment of Duchenne muscular dystrophy. Cell Immunol.
2010;260(2):75-82).  The reason why cord blood appears to be useful in
treatment of a variety of conditions is believed to be due, at least in part, to
ability of the cells to produce numerous therapeutic factors that stimulate stem
cells already in the body to start multiplying.  Additionally, numerous studies
have shown that cord blood derived stem cells can produce cells ranging from
liver to brain to heart muscle.  A description of cord blood stem cells may be
seen on this video

http://www.youtube.com/watch?v=z6CP-OL1Kuc .

Dr. Hoon Han, AmStem’s Chairman, commented on the cord
blood bank, "With more than 1.1 million foreigners now living in Korea, the
number of multicultural marriages and families is on the rise. By providing
these families the opportunity to store the donated umbilical cord blood, we
give them access to autologous stem cells that may be used in the future
treatment of certain cancers, such as leukemia, as well as immune and genetic
disorders. In addition, by addressing the multicultural population in Korea,
this collaborative opportunity also increases the genetic diversity of the
available supply of umbilical cord blood derived stem cells — which may benefit
Korean and foreign patients alike."

Filed Under: Adult Stem Cells, Cord Blood Stem Cells, 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

Butyrate Greatly Enhances Derivation of Human Induced Pluripotent Stem Cells by Promoting Epigenetic Remodeling and the Expression of Pluripotency-Associated Genes

Generation of inducible pluripotent stem cells (iPS) offers
the possibility of creating patient-specific stem cells with embryonic stem cell
therapeutic potential from adult sources.  Recently the main hurdle of iPS cell
generation, the need for introduction of oncogenes in the adult cells, has been
removed by use of chemical modulators as well as alternative non-cancer causing
genes.  Another drawback of creating iPS cells is the need for mass screening of
many transfected target cells before identification and extraction of the
correct cell can be made.  In the current paper the histone deacetylase
inhibitor butyrate was used to enhance potency of iPS generation in vitro. 
Histone deacetylase inhibitors are a type of compounds that decrease the density
of DNA in chromosomes.  By performing this function the DNA because more
amenable to reprogramming, in the sense that the cells can be coaxed to
de-differentiate with less effort.  Another histone deacetylase inhibitor,
valproic acid, which is used clinically to treat convulsions, has been shown to
increase the ability of blood making stem cells to self-replicate with higher
efficiency, which is a characteristic of earlier de-differentiation.    

In a recent paper it was demonstrated that temporary
treatment with butyrate increases efficacy of iPS generation by 15-51 fold using
two techniques that are commonly used for generation of these cells.  It was
demonstrated that in the presence of butyrate stimulation a remarkable (>100-200
fold) increase on reprogramming in the absence of either KLF4 or MYC transgene.

This suggests that butyrate may be a useful agent to
incorporate in the iPS generation protocols that are currently under
development.  Furthermore, butyrate treatment did not negatively affect
properties of iPS cell lines established. The generated iPS cell lines,
including those derived from an adult patient with sickle cell disease by two
methods show normal karyotypes and pluripotency.

To mechanistically identify molecular pathways of butyrate
enhancement of iPS generation, the investigators performed conducted genome-wide
gene expression and promoter DNA methylation microarrays and other epigenetic
analyses on established iPS cells and cells from intermediate stages of the
reprogramming process.

 By day 6-12 after exposing cells to butyrate, enhanced
histone 3 acetylation, promoter DNA demethylation, and the expression of
endogenous pluripotency-associated genes including DPPA2, whose over-expression
partially substitutes for butyrate stimulation is known.

According to Dr. Mali " Thus, butyrate as a cell
permeable small molecule provides a simple tool to further investigate molecular
mechanisms of cellular reprogramming. Moreover, butyrate stimulation provides an
efficient method for reprogramming various human adult somatic cells, including
those from patients that are more refractory to reprogramming"

Methods of increasing efficacy of iPS generation have
included not only chemical manipulation but also starting from cell sources that
are generally considered more immature.  For example a previous study
demonstrated that mesenchymal stem cells create a much higher per-cell number of
iPS cells as compared to skin fibroblasts. 

One of the interesting points of this finding is that
butyrate may theoretically be useful at expanding potential of stem cells
already in an organism.  Since butyrate is used clinically for treatment of urea
cycle disorders and is non-toxic at pharmacological doses, it may be a good
candidate for expanding stem cells in vivo.  Manipulation of the stem cell
compartment by administration of therapeutic agents has already been performed
for mobilization, which has been published with the neutraceutical Stem-Kine

http://www.translational-medicine.com/content/pdf/1479-5876-7-106.pdf.

Filed Under: Adult Stem Cells, Embryonic Stem Cells, 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: , , , ,
March 3, 2010 by

The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells

Embryonic stem cells possess the ability to propagate in
tissue culture indefinitely.  This is different than differentiated cells, for
example, skin cells which can only multiple in tissue culture approximately 50
times before undergoing senescence.  The ability of embryonic stem cells to
escape senescence is related to expression of the protein telomerase.  Usually
when cells multiply the ends of the chromosomes, called telomeres, progressively
reduce in size.  When the telomeres become critically short, the gene p53 is
activated, which is involved in instructing the cells to stop multiplying and
exist in a semi-alive state called senescence.  Tumor cells and embryonic stem
cells escape senescence by expressing the enzyme telomerase.  This enzyme
essentially allows cells to repair their telomeres by progressively adding new
nucleic acids.  Although much is known about senescence or lack thereof in adult
cells and embryonic stem cells, little research has been performed in whether
inducible pluripotent stem cells (iPS) can also escape proliferative
senescence.  In a recent publication this question was examined.

In a similar manner to embryonic stem cells, iPS cells were
shown to express high levels of the enzyme telomerase, and propagation in tissue
culture was achieved up to 200 passages without senescence occurring. 
Furthermore the investigators studied the mitochondrial stress pathway.  It was
found that somatic mitochondria within human iPSCs revert to an immature
ESC-like state with respect to organelle morphology and distribution, expression
of nuclear factors involved in mitochondrial biogenesis, content of
mitochondrial DNA, intracellular ATP level, oxidative damage, and lactate
generation. When iPS cells were differentiated into adult cells, mitochondria
within iPSCs demonstrated maturation and anaerobic-to-aerobic metabolic
modifications. This same finding was observed in embryonic stem cells. 

These data suggest that iPS cells possess several important
properties similar to embryonic stem cells, which further supports the
possibility of interchangeably using ES and iPS cells for experimental purposes.
The next question is whether iPS cells may be generated in large quantities so
that their mitochondria may be transferred to aged cells. 

Another interesting finding in the current study is that
the metabolic pathway used by both iPS and embryonic stem cells is analogous to
that found in cancer cells.  Therefore it will be interesting to follow studies
using iPS as a model of cancer.

Filed Under: Embryonic Stem Cells, News, Stem Cell Research Tagged With: , , , , ,
March 1, 2010 by

Dallas doctor uses stem cell injections in cosmetic surgery

 

Dr. Jeffrey Caruth, a Texas OBGYN who is performs cosmetic
surgery has started using adult stem cells to increase the effectiveness of "fat
grafting".  The use of fat as a filler has been used in plastic surgery for
decades.  The only problem has been that as time passes, the fat gets resorbed
by the body.  A publication from Japan (Yoshimura et al. Cell-assisted
lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived
stem cells. Dermatol Surg. 2008 Sep;34(9):1178-85) demonstrated that if fat
stem cells are mixed in with the fat, the rate of resorption is markedly
diminished.  Given that the cells administered are the same cells of the body,
the possibility of immunological reaction is absent. 

 Jackie Jones is the second patient in North Texas to
undergo this type of cosmetic surgery.  "I will be happy to see the lines on my
face go away," she said. "I will be happy with the new shape of my body and that
in itself is really exciting to me."

Dr. Caruth said stem cells help solve a problem that has
plagued prior procedures. "The problem has been with traditional fat grafting
that you put a volume of fat into the face, the buttocks and then in a month or
two or three there is significant volume loss due to death of the fat cells you
put in,"  he continued "You’re going to get twice the graft survival versus
other methods," Caruth said.

 It is known that conventional artificial filler injections
usually last up to a year and regular fat grafting lasts anywhere between three
to five years.  It is anticipated that addition of stem cells will allow the
grafts to maintain shape for up to 10 years.

 Dr. Jeffrey Kenkel, the vice chairman of plastic surgery
with UT Southwestern, stated "There is a tremendous amount of excitement about
stem cells," he said. "We just don’t have a lot of information about them, about
how they work and how we control them to do what we want them to do."

 After the procedure Jones commented "I can really tell a
difference. The lines between my eyebrows are gone."

Human fat contains not only stem cells but other cells such
as T regulatory cells that control inflammation.  Given that inflammation is
associated with aging, there may be several mechanisms at play responsible for
the effects seen by addition of fat stem cells to fat grafts.  An example of fat
stem cells exerting therapeutic effects can be seen in multiple sclerosis as
reported in this publication

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

Filed Under: News, Stem Cell Therapy Tagged With: , ,
March 1, 2010 by

Cord blood stem cells help meet minority marrow needs

Leukemias are cancers of the cells that give rise to white
blood cells.  For example in myeloid leukemias the cells that normally would
become the blood cells neutrophils or macrophages start to make copies of
themselves but refuse to mature.  What happens is that the body is flooding with
cells that on the one hand do not protect the patient from disease, and on the
other hand start to interfere with organ function.  In lymphocytic leukemias the
cells that give rise to lymphocytes such as T and B cells, stop maturing. 
Despite advances in our knowledge of the molecular basis for many leukemias, in
many situations the only definitive cure can be achieved through stem cell
transplantation. Traditionally this has been performed using bone marrow stem
cells from donors that are matched with recipients.  The process of
transplantation involves initial destruction of the recipient bone marrow and
leukemic cells by administration of high doses of radiation and chemotherapy. 
Subsequently donor bone marrow is given which contains high numbers of stem
cells.  These donor stem cells eventually take over the function of making blood
and the recipient is cured of leukemia but has someone else’s stem cells inside
of them.

One of the major barriers to complete success of bone
marrow transplantation is that donors must be matched very strictly.  If the
donor is not matched then the immune cells in the bone marrow start to attack
the recipient.  This is called graft versus host disease, and is one of the most
devastating side effects of bone marrow transplantation, which in some cases is
lethal.

The current story from CNN describes a personal experience
of a lady, Diana Tirpak, who could not find a bone marrow donor.  In general it
is rather difficult to find an unrelated matching donor.  In minorities the
process is even more difficult.  Tirpak, a retired school nurse in Hudson, Ohio
was so convinced that the search for a donor was futile that she helped her
husband buy a suit for her funeral.  "I was bound and determined he was going to
look fine at the funeral," she said. 

Fortunately advances in "alternative sources" of stem cells
have saved Tirpak’s life.  While it is known that stem cells reside in the bone
marrow, another source that is only in recent times being appreciated is cord
blood.  Originally cord blood transplantation was restricted to children since
the number of stem cells per cord is relatively small.  However new advances in
transplantation, as well as introduction of "two cord" approaches have opened up
this procedure for adults.

Dr. Mary Laughlin, founder and medical director of the
Cleveland Cord Blood Center stated "Cord blood is rich in stem cells and easier
to match than adult bone marrow because the immune cells are not developed.
Also, patients can get the treatment in about three weeks — as opposed to six
to eight for bone marrow from an adult donor.  That can be a critical time
interval for a patient who is in remission," she said, noting that doctors often
fear a patient’s relapse while awaiting the transplant.

To get a sense of how difficult it is to find bone marrow
donor matches, the National Bone Marrow Registry has more than 12 million donors
that meet the needs of only about 60 percent of Caucasians in the United
States.  In contrast, only 5 to 15 percent of minorities have available donors. 

Another example of the difficulties minorities face in
obtaining a suitable donor is the story of Nathan Mumford, who is
African-American and was diagnosed with leukemia shortly after finishing
college.  "We went through that process, and nobody had a match. Siblings are
the best matches. My brother or my sister wasn’t a match. My friends, aunts,
uncles, cousins, nobody was a match. So, couldn’t go that route," Mumford said. 
Luckily he too was eligible for a cord blood transplant.  "That was an
opportunity," said Mumford, who survived Hodgkin’s disease as a child. "That was
a chance for me to live. I’m not a quitter. I’ve never been a quitter, so I
wasn’t going to quit."

In November of 2004 he was treated by cord blood
transplantation.  Now his leukemia is cured and he claims he is in great shape. 
I just feel amazing," he said. "I have a lot of energy, and I’m just excited
about it."

The use of cord blood transplants among unrelated donors
have risen from 1 percent in 2001 to 24 percent last year, Dr. Laughlin says.

It should be noted that the use of cord blood for leukemias
is different than its use for other conditions that do not need destruction of
the recipient’s bone marrow.  For example in patients with heart failure there
is a need for stem cells that can either directly give rise to new heart cells,
or produce growth factors that activate stem cells in the heart.  The use of
cord blood derived stem cells for heart failure has yielded some positive
results in animal studies and in several individual case reports as seen in this
video

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

Filed Under: Adult Stem Cells, Cord Blood Stem Cells, News, Stem Cell Research 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: , , , ,
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