Scientists look to stem cells to mend broken hearts

Cardiac medicine has traditionally been associated with innovative procedures that sometimes where considered heretical to the present day dogma. For example, the first heart transplant, the use of the balloon catheter, the introduction of thrombolytics, all met substantial resistance from the “establishment” in their time. It appears that the next revolution in cardiac medicine is the use of stem cells. Aside from the obvious ethical and moral dilemmas surrounding embryonic tissues, the major controversy has been the belief that heart tissue does not repair itself after it has been lost. However, slowly but surely it appears that support behind the use of stem cells for heart conditions is gaining momentum.

One sign of this is the recent announcement that Britain’s leading heart charity, the British Heart Foundation (BHF), launched a 50 million pound ($80 million) research project into the potential of stem cells to regenerate heart tissue and “mend broken hearts”.

“Scientifically, mending human hearts is an achievable goal and we really could make recovering from a heart attack as simple as getting over a broken leg,” said Professor Peter Weissberg, medical director at the BHF.

One example of research in this area being performed in England is the work of Professor Paul Riley of the Institute of Child Health at University College London (UCL) who has identified a natural protein, called thymosin beta 4, that plays a role in developing heart tissue. He said his researchers had already had some success in using this protein to “wake up” cells known as epicardial cells in mice with damaged hearts. “We hope to find similar molecules or drug-like compounds that might be able to stimulate these cells further,” he told reporters at the briefing.

Currently the most advanced type of stem cell therapy for the heart involves administration of the patient’s own bone marrow cells into the area of heart damage after a heart attack. This work, which was performed in England and internationally, seems to suggest that cardiac muscle may be preserved when cells from the bone marrow produce various growth factors that stimulate stem cells that are already existing in the heart.

Other methods of administering stem cells into the heart include direct injection into the heart muscle during bypass surgery. This is performed experimentally in patients with severe angina on the hope that the injected stem cells will provide support for formation of new blood vessels, called collaterals, which are anticipated to increase the blood flow to the heart and thereby reduce angina.

Currently embryonic or fetal derived stem cells have not been used for treatment of heart conditions in humans. Therefore, at least for now, ethical issues do not seem to be a major obstacle to advancement of stem cell medicine for hearts.

Stem Cell Institute in Panama Collaborates on New Method of Treating Diabetes-Associated Heart Disease

Zhang et al. Journal of Translational Medicine

Diabetes is associated with numerous “secondary complications” including premature heart disease, renal failure, critical limb ischemia (an advanced form of peripheral artery disease) and diabetic retinopathy. One of the common features of these secondary complications is that they are all associated with low levels of circulating endothelial progenitor cells. We have previously discussed the interaction between inflammation and low levels of circulating endothelial progenitor cells http://www.translational-medicine.com/content/7/1/106. It appears that the uncontrolled sugar levels in the blood cause generation of modified proteins, which initiate low level, chronic inflammation. One of the major mechanisms by which sugar- modified proteins induce inflammation is by stimulating a molecular signaling protein called Toll like receptor (TLR)-4. Generally TLR-4 is used by the body to sense “danger”, that is, to sense pathogens, tissue injury, or various factors that may negatively affect the well-being of the host.

In a collaborative study between Stem Cell Institute Panama, Medistem, and the University of Western Ontario, Canada, it was observed that TLR-4 is associated with induction of heart cell (cardiomyocyte) death in diabetic animals. The scientists demonstrated that suppressing the gene encoding for TLR-4 resulted in prevention of heart disease. The results were published in the article Zhang et al. Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4. J Transl Med. 2010 Dec 15;8(1):133. TLR-4 is known to recognize bacterial endotoxin, fragments of degraded extracellular matrix, as well as the stress protein HMBG-1.

In the current experiment, mice were made diabetic by administration of the islet-specific toxin streptozotocin. Diabetic mice were treated with double stranded RNA specific to the gene encoding TLR4. It is known that when cells are treated with double stranded RNA, the gene that is similar to the double strand is silenced. This process is called “RNA interference”.

Seven days after mice became diabetic, as evidenced by hyperglycemia, the level of TLR4 gene in myocardial tissue was significantly elevated. This suggested that not only does hyperglycemia activate TLR4, which was previously known, but that expression of this pro-inflammatory marker actually is increased. Indeed it may be possible that triggers of TLR4 actually act in an autocrine manner in order to increase cell sensitivity

In order to determine whether TLR4 was associated with the cause of cardiomyocyte death, animals were administered the double stranded RNA in order to suppress levels of TLR4. When this was performed the level of cardiomyocyte death was markedly reduced. This is an important finding since usually scientists think of TLR4 as a molecule that activates inflammation through stimulation of the immune

The authors conclude by stating that new evidence is presented suggesting that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.

The research finding that TLR4 is implicated in death of cardiac cells means that agents that suppress it, such as double stranded RNA, may be useful for incorporation into stem cells in order to make the cardiac cells that are derived from the stem cells resistant to death induced by conditions of stress such as hyperglycemia.

Stem cell therapy benefits patients with chronic heart failure—study

(Neharika Sabharwal) After a heart attack the myocardium (heart muscle) undergoes a period of damage during which cells of the body attempt to heal the injured tissue. This occurs through stem cells found in the heart itself, called cardiac specific stem cells (CSC) as well as bone marrow stem cells which seem to exit the bone marrow, enter circulation, and migrate towards the area of cardiac damage.

Given that the bone marrow stem cells seem to both directly become new heart cells, as well as stimulate formation of new blood vessels that accelerate the healing process, it may be theoretically beneficial to administer bone marrow stem cells to patients after a heart attack. Administration of stem cells is usually performed in these patients by means of a balloon catheter. This device temporarily occludes the artery that is feeding the blood vessel that provides circulation to the area of the injured muscle. While occlusion is occurring cells are administered. This allows the cells to enter the cardiac circulation in a highly concentrated manner. This type of stem cell therapy is termed “post-infarct intracoronary administration of stem cells”.

The use of intracoronary bone marrow transplantation has been published in many clinical trials with overall success in stimulating heart muscle function as judged by the left ventricular ejection fraction. Additionally, bone marrow stem cells have been demonstrated to reduce pathological remodeling by inhibiting the dilation of the ventricles that occurs after a heart attack.

While short-term effects of bone marrow stem cell administration are well-known, little is known about long term effects. A recent study, called the STAR Heart Study, aimed to compare bone marrow cells versus optimal conventional therapy in patients with heart failure due to healed myocardial infarction.

The study demonstrated that intracoronary bone marrow stem cell therapy not only improves ventricular performance and quality of life but also the long term rate of survival in patients with chronic heart failure, claims a new study.

According to researchers, the beneficial effects of stem cell therapy were perceived within three months of the treatment and the effect continued for well over five years. Lead scientist of the study, Bodo-Eckehard Strauer of Duesseldorf’s Heinrich Heine University in Germany said, “Our study suggests that, when administered as an alternative or in addition to conventional therapy, bone marrow cell therapy can improve quality of life, increase ventricular performance and increase survival.”

Currently several companies are developing devices that allow for the use of patient’s own stem cells for intracoronary administration post infarct. One such company is the Hackensack NJ based Amorcyte Inc, which uses standard bone marrow extraction procedures, isolates CD34 positive cells using the Baxter Isolex device, and subsequently infuses the isolated cells using a catheter based technique. The company Aldagen is also performing a similar procedure, however instead of purifying stem cells based on CD34 they are using aldehyde dehydrogenase expression as a means of isolating stem cells from non-stem cells from the bone marrow.

The STAR study was reported at the ‘European Society of Cardiology (ESC) 2010 Congress. It tracked 391 patients with chronic heart failure because of ischemic heart disease following a heart attack. Out of 391 patients, 191 agreed to have the bone marrow stem cell treatment. The remaining 200 who refused therapy participated as the control group.

The patients were monitored for a period of five years after bone-marrow-cell therapy with results at 3 months, one year and five years showing a significant difference between the treatment and control group. At five years only 7 patients who received stem cells died, as compared to 32 in the control group. No treatment associated adverse events of a serious nature were observed.

Dr Mariell Jessup, medical director of the Penn Heart and Vascular Center at the University of Pennsylvania stated, “The hope is that by injecting stem cells into the scarred area, you will bring life back to that area and induce healthy muscle…There’s been ongoing excitement about using stem cells to treat heart disease for some time and this study certainly adds to it.”

Success Stems From Adult Cells

The use of adult stem cells for conditions besides bone marrow transplant is most prevalent in the area of heart failure. Since the original study of Strauer et al in 2001 in which a 46-year old patient was administered bone marrow stem cells after a heart attack and experienced a profound improvement in cardiac function, more than a thousand patients have received adult stem cells for cardiac-associated conditions.

Today the story of Eddie Floyd, a small business owner from Austin, Texas was highlighted in an article describing his presentation to the Texas Alliance for Life. Mr. Floyed suffered a heart attack three years ago. The heart attack caused profound damage so as to make him eligible to participate in a clinical trial being conducted at the Texas Heart Institute using his own bone marrow stem cells. The trial involves administration of the stem cells using a special catheter to the blood vessels supplying the heart muscle.

Three years later, Mr Floyd is happy with the results. He explains that he has been able to resume normal daily activities. "There really isn’t anything that I can’t do because of my heart, that I’m aware of. [But] there are a few things I can’t do because of my belly…,"

Since the stem cells are from the patient’s own body, there is no possibility of rejection. He stated "They did not cause any kind of rejection, so I didn’t have to have any rejection-preventive medicine or anything like that…They were just generic stem cells that became heart."

In his talk Mr. Floyd explained that despite all of the media publicity and controversy around embryonic stem cells, these cells produced no benefit to patients like himself. There was one clinical trial in embryonic stem cells that was approved, which was Geron’s spinal cord injury protocol. The approval, however, was retracted before any patients were treated.

In contrast, adult stem cells such as the ones derived from the bone marrow have been used successfully not only in the treatment of heart failure, but other diseases such as liver failure, type 2 diabetes, and prevention of amputation in patients having poor circulation in the legs.

Currently adult stem cells are in clinical trials in the US and Western Europe. The most advanced adult stem cell types are in Phase III of trials, meaning that
if successful they will be sold as a drug within the next 1-3 years. Because Phase III trials have a placebo control arm, some patients do not want the risk
of being in a placebo group and therefore choose to go to clinics outside the US that offer this treatment. Once such clinic, Cellmedicine, has published
results on patients, such as a recent heart failure patient who underwent a profound recovery in heart function after treatment. The patient is described
in the peer reviewed journal International Archives of Medicine which is freely accessible at
www.intarchmed.com/content/pdf/1755-7682-3-5.pdf.

Stem Cell Institute Panama Clinic Case Report of Successful Treatment of Heart Failure Patient Published

Adult stem cell therapy is currently in numerous clinical trials in the United States and Internationally. A sample of ongoing trials can be seen at
www.clinicaltrials.gov if you search for the words "stem cell". In clinical trials the objective is to determine safety (in Phase I), efficacy in an unblinded manner (Phase II) and efficacy in a blinded manner (Phase III). Numerous stem cell clinical trials are in Phase II, meaning that although safety has been established there is a question of efficacy. Patients with terminal
diseases sometimes make the informed decision not to wait until efficacy trials are completed and to go to stem cell clinics that offer similar procedures being
performed in clinical trials, but without the risk of offering the patient a placebo. The additional benefit to patients of making this choice is that they are offered treatment rapidly, whereas getting into a clinical trial could mean months on a waiting list.

The stem cell clinic Cellmedicine has been offering this choice to patients. Unlike other stem cell clinics, Cellmedicine has made it a priority to publish its protocols, scientific rationale, and outcomes in the peer reviewed literature. This means that all the scientists and doctors in the world can learn about the work being performed at Cellmedicine and offer comments/suggestions on it.

Today Cellmedicine announced publication of a paper in the peer reviewed journal, International Archives of Medicine, of a patient with terminal heart failure who underwent profound recovery after receiving adult stem cell therapy. The publication is freely available at

http://www.intarchmed.com/content/pdf/1755-7682-3-5.pdf
.

The patient discussed in the report was administered adult stem cells in November 2007, when his heart had an ejection fraction of 25-30%. The ejection fraction is a quantitative measurement of the heart’s pumping activity. On June 2008, August, and Oct 2009, this marker of function increased to 40%. The patient reported a major improvement in quality of life. Additionally, proteins in the blood associated with heart failure were decreased.

Given that the report was based on only one patient, doctors at the clinic are excited but still caution in their statements.

"Stem cell therapy is a new science, and although the results discussed in the paper are promising, only the conduct of double-blinded, placebo controlled trials will allow definitive conclusions to be drawn," said Dr. Paz Rodriguez, Medical Director of the Cellmedicine Panama clinic and coauthor of the study.

In the publication, Cellmedicine provides detailed rationale for how the stem cell therapy may be affecting the process of heart failure. Data from other studies was described which states that stem cells can:

a) Directly differentiate into new heart cells

b) Stimulate the body’s ability to generate new heart muscle by activating dormant stem cells that already exist in the heart

c) Cause formation of new blood vessels that accelerate the healing process.

Heart failure is only one of the conditions that Cellmedicine treats.

"To date our group has published results on multiple sclerosis, non-ischemic heart failure, and Duchenne Muscular Dystrophy patients in collaboration with major
American Universities including University of California San Diego, Indiana University, and University of Utah. By publishing our data in a scientific forum, we welcome discussion and interaction, which will lead to advanced patient care not only in Panama City but internationally," concluded Dr. Paz Rodriguez.

Stem Cells Don’t have to be Alive to Be Beneficial

The use of stem cells in patients who have poor circulation
is well-known.  In fact, the first use of stem cells for conditions other than
blood disorders was in patients who were undergoing bypass surgery.  Usually
patients undergo bypass because of advanced atherosclerosis that is inhibiting
the flow of blood to the heart muscle.  Despite success of bypass surgery, the
underlying problem of thickened blood vessels remains.  Japanese scientists (Hamano
et al. Local implantation of autologous bone marrow cells for therapeutic
angiogenesis in patients with ischemic heart disease: clinical trial and
preliminary results. Jpn Circ J. 2001 Sep;65(9):845-7
) in 1999 treated 5
patients with ischemic heart disease with their own bone marrow cells injected
into the heart muscle during bypass.  Of these 5 patients, 3 demonstrated
increased blood flow at the area where the stem cells were injected.  Subsequent
to this numerous clinical trials have been conducted using bone marrow stem
cells for increasing circulation both to the heart and also to legs that lack
proper blood flow (particularly in patients with critical limb ischemia see
video

http://www.youtube.com/watch?v=dcCwZ4CsiKc
). 

One of the major questions has always been how the injected
stem cells improve circulation.  Originally the idea was that the stem cells
become new blood vessels, and that these new blood vessels take over the
function of the older blood vessels.  However, recent data suggests that the
stem cells injected actually collaborate with the stem cells that are already in
the patient.  For example, it was demonstrated that in patients lacking oxygen
in their legs who receive bone marrow stem cell therapy, the responders actually
have increased levels of their own circulating stem cells.  Here is a video
describing this

http://www.youtube.com/watch?v=OwIOL13vXQ4
.

It is believed that bone marrow stem cells, particularly
mesenchymal stem cells, are capable of producing proteins that stimulate the
body’s own stem cells into making new blood vessels.  These proteins include
IGF-1, VEGF, and HGF. 

A recent study from Stanford University (Hoffmann et al.
Angiogenic Effects Despite Limited Cell Survival of Bone Marrow-Derived
Mesenchymal Stem Cells under Ischemia. Thorac Cardiovasc Surg. 2010
Apr;58(3):136-142
) should to investigate the cellular and molecular
interactions which are associated with formation of new blood vessels after
administration of bone marrow mesenchymal stem cells.

The investigators first began by assessing production of
the protein VEGF from bone marrow mesenchymal stem cells under conditions of
normal oxygen, and under reduced oxygen conditions.  The idea being that if
mesenchymal stem cells are responsible for producing growth factors, then it
would make sense that production of these factors would increase in response to
needs of the body (eg reduced oxygen).  As a control, fibroblast cells were
assessed side by side with the mesenchymal stem cells.  It was found using in
vitro experiments that mesenchymal stem cells produced much higher levels of
VEGF under hypoxia as compared to fibroblasts, however, mesenchymal stem cells
died faster than fibroblasts in response to hypoxia.

To determine whether mesenchymal stem cells or fibroblasts
cause formation of new blood vessels in animals, a model of critical limb
ischemia was developed in which the artery feeding the leg of mice was ligated. 

One week after induction of ischemia in the leg, 1 million
mesenchymal stem cells, or fibroblasts were injected into the muscles of the
animals.  The cells were labeled genetically so that the injected cells could be
distinguished from the endogenous cells. 

Substantially elevated levels of new blood vessels, and
improved circulation, was observed in the mice that received mesenchymal stem
cells as compared to fibroblasts.  Interestingly, at 3 weeks after
administration, despite improved circulation, the mice receiving mesenchymal
stem cells had much lower numbers of injected cells as compared to mice that
received fibroblasts.

This study suggests that mesenchymal stem cells seem to use
the natural mechanisms of the body in order to generate new blood vessels. 
Something else of interest from this study is that fibroblasts live longer in
hypoxia as compared to mesenchymal stem cells.  Hypothetically it may be
possible to transfect fibroblasts with genes that stimulate production of new
blood vessels.  Unfortunately, the proper combination of growth factors and
concentration are still not known for creation of new blood vessels.

Magnetic Attraction of Stem Cells to Injured Heart Creates Potent Treatment

The intracoronary administration of bone marrow stem cells in patients who have suffered a heart attack has been demonstrated to cause beneficial effects in double blind studies, as discussed in this video http://www.youtube.com/watch?v=flv0RmzPyLU. Intracoronary administration has potential side effects since a balloon needs to be expanded in the area where the heart attack occurred, which may cause exacerbation of the existing damage. A more attractive method of stem cell delivery would be via the intravenous route. Unfortunately, intravenous administration has the drawback that some of the cells become lodged in organs such as the lung and liver.
Despite this, intravenous administration has demonstrated positive results, for example in a clinical trial conducted by Osiris (Hare et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86) an improvement in heart pumping
ability was observed.

One way of improving stem cell homing to the area of need is through direct administration of proteins, or genes encoding the proteins, that specifically attract stem cells. This approach has been performed with SDF-1 in animal models, and now the company BioHeart is doing Phase I clinical trials. Other ways include the use of laser therapy to induce expression of stem cell homing molecules as being developed by the San Diego company Entest Biomedical.

Today a new approach was reported in the journal Circulation Research, which is published by the American Heart Association.
Scientists at Cedars-Sinai Heart Institute have loaded stem cells with iron-nanoparticles and administered them intravenously in animals that were induced to undergo a heart attack by ligation of the coronary artery. The scientists found that by
applying magnetic fields to the heart, they could increase the number of injected stem cells that lodged into the heart by 3-times. This was accompanied by functional improvement.

"Stem cell therapies show great promise as a treatment for heart injuries, but 24 hours after infusion, we found that less than 10 percent of the stem cells remain in the injured area. Once injected into a patient’s artery, many stem cells are lost due to the combination of tissue blood flow, which can wash out stem cells, and cardiac contraction, which can squeeze out
stem cells. We needed to find a way to guide more of the cells directly to the area of the heart that we want to heal." Said Eduardo Marban, M.D., director of the Cedars-Sinai Heart Institute.

Commenting on the success of the present study, he stated "This remarkably simple method could easily be coupled with current stem cell treatments to enhance their effectiveness."

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
.

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
."

Adult Stem Cell Companies Seen as Profitable Investment

While religious groups debate the various ethical issues of embryonic versus adult stem cells, and researchers debate the various scientific issues, financial analysts are not debating at all. From a purely monetary perspective, it is adult stem cells, not embryonic stem cells, which constitute a sound investment.

As the authors of today’s article point out, "Amid controversies over embryonic stem cell research, drugs using adult cells are already bearing fruit." As the authors continue to explain, "When it comes to stem cells, the public – and the media – tend to focus on embryos. But researchers and analysts say marketable therapies already are emerging from less controversial work with adult stem cells."

Such a fact is hardly a secret, as scientists and physicians have been trying to tell the world for years that adult stem cell therapies already exist, while embryonic stem cell therapies do not, and probably will not for at least another decade. Such information is often "translated" through the filters of the media, however, many members of whom seem to be heavily biased toward the word "embryonic". Apparently it takes a financial perspective to convey the point that adult stem cells are scientifically and medically viable as human therapies, whereas embryonic stem cells are not. As the authors of today’s investment article explain, "Adult cells make up the lion’s share of the stem cell space, mainly because they are easier to come by than embryonic cells, and less expensive to run in clinical trials. They are also derived from mature tissue, like bone marrow or umbilical cord blood, so they avoid the ethical debate that surrounds embryonic stem cells."

The authors go on to point out that adult stem cells can "combat a variety of maladies from diabetes to heart disease", and "In fact, adult stem cells are currently the only type of stem cells used in transplants to treat diseases, such as cancers like leukemia. Furthermore, researchers are far closer to commercializing drugs based on adult stem cells than any product based on embryonic stem cells." Such medical and scientific advances did not suddenly happen overnight, but in fact have been going on for years. Where have you been, members of the media???

Ethics and politics aside, the scientific differences between embryonic and adult stem cells are numerous and significant, which is precisely why financial analysts are cautioning investors to heed the differences when it comes to market and monetary considerations. One financial guru in particular, Robin Young, a medical industry analyst with RRY Publications, has estimated that gross sales of adult stem cell therapies will surpass $100 million in the U.S. alone, just in 2009. In less than a decade, by 2018, Mr. Young has calculated that revenue from adult stem cell therapies could exceed $8.2 billion. Embryonic stem cells, by contrast, are not expected to advance beyond the laboratory stage for at least another decade, at the earliest, due to the numerous inherent problems that plague embryonic stem cells, not the least of which is their strong tendency to form teratomas – a particularly hideous type of tumor that contains teeth, hair, bones and bodily organs in a grossly disorganized fashion, like a disassembled and randomly rearranged human embryo. Even Dr. James Thomson, the world authority on embryonic stem cells, repeatedly emphasizes the point that embryonic stem cells are notoriously problematic in the laboratory and therefore will require at least another decade of research before being safe enough to be considered clinically viable as therapies. As "the father of embryonic stem cell science", and the first person who ever isolated an embryonic stem cell in the laboratory, Dr. Thomson certainly knows what he’s talking about, although most members of the media seem uninterested in such a dismal prospect for embryonic stem cells, so the disadvantages of these highly volatile and dangerous stem cells are rarely reported. But for anyone who may be interested either in being treated as a patient with stem cells, or in investing money in stem cells, the scientific realities become immediately relevant and important. While such realities are certainly discouraging for embryonic stem cells, they are highly encouraging for adult stem cells. As stated in today’s article, "Indeed, several pharmaceutical companies are now taking notice of research advancements in adult stem cells – and their proximity to reaching the market."

According to Debra Grega, executive director of the Center for Stem Cell and Regenerative Medicine at Case Western Reserve University, "Adult-derived cells are the ones that have been studied for the past 10 to 15 years and are ready for prime time. Large pharmaceutical companies are now wanting to get into the adult stem cell therapeutic area. That indicates to me that there is enough safety and enough efficacy that they are willing to put money in."

By sharp contrast, as the authors of today’s article point out, "The California-based outfit Geron dominates the embryonic market, and is perhaps 10 years away from commercializing a spinal cord treatment based on its research."

Another example of the momentum behind adult stem cell therapies is found in the pharmaceutical giant Pfizer which announced in November of last year that it would invest $100 million in regenerative medicine research over a 3 to 5 year period, with a strong emphasis on adult stem cells. Additionally, as the authors of today’s article explain, "The frontrunner in the adult stem cell space is Osiris Therapeutics. Last year, the biotech Genzyme paid Osiris $130 million up front, with another $1.2 billion to be paid in potential milestones, to develop two new adult stem cell treatments. Osiris’s star drug Prochymal is used to fight graft-versus-host disease, a painful illness that can afflict transplant recipients. Osiris says the FDA could approve the drug within a year. If successful, Osiris would be the first company to win approval for a stem cell drug."

Among other adult stem cell companies mentioned in today’s article are Stem Cells Inc., Cytori, and Aastrom Biosciences, all of which are described as "moving forward in the adult stem cell space."

As the authors conclude, "And so while there’s just one star in the embryonic stem cell universe, a whole constellation of adult stem cell drugs could be just around the corner."

Rather than having to wait another entire decade, or longer, for what may or may not even be a profitable return on one’s investment in the embryonic stem cell field, a wiser investment strategy would target any of the numerous companies that already have adult stem cell therapies in FDA-approved clinical trials, and which are moving increasingly closer to legal commercialization in a virtually unlimited market which is entirely untapped.