Successful Stem Cell Treatment Of Autoimmune Diseases


Recent findings published in the Journal of Translational Medicine report the first ever treatment of autoimmune diseases with fat-derived stem cells. The article is entitled “Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells,” and contained contributions from researchers in five different countries: South Korea, United States, Japan, China, and Germany.

The senior author, Jeong Chan Ra, president of RNL Stem Cell Technology Institute, and his collaborators were successful in treating patients with autoimmune diseases who had experienced severe tissue damage as a result of their diseases and had limited treatment options.

Autoimmune diseases are caused by mis-regulation of the immune system that allows the body’s immune system to attack the very tissues and organs that house it. There are different kinds of autoimmune diseases which include systemic lupus erythematosis, rheumatoid arthritis, multiple sclerosis, autoimmune hearing loss, spastic myelitis, Bechet’s syndrome and so on.  Symptoms of autoimmune diseases are long-term, and these diseases often caused permanent damage.

In previous work, Ra’s team demonstrated the safety of intravenously infused adipose (fat)-derived stem cells in humans. Patients who received multiple stem cell infusions showed no adverse effects and no severe side effects. In this present study, the team showed that infusions of these stem cells were effective in treating diseases that ranged from autoimmune hearing loss, multiple sclerosis, polymyositis, atopic dermatitis, and rheumatoid arthritis, in this study.

In the case of autoimmune hearing loss, the patient was administered with her own stem cells. Her hearing returned to normal (scaled out to 15 decibels) even though she had previously not responded to steroid treatments.

A multiple sclerosis patient suffered severe side effects from high dose steroid treatments and had difficulty walking. However after infusions of her own stem cells, her condition improved tremendously, and she was able to move her legs using her own muscular strength.

Other autoimmune diseases treated in this paper were patients with multiple sclerosis, atopic dermatitis, and rheumatoid arthritis, all of whom were not able to be treated with existing medication. However, after multiple infusions of their own fat-derived stem cells, their illnesses became manageable.

Researchers are continuing to develop sophisticated stem cell technology using five grams of fat as a standard, which can be expanded to 1 billion stem cells. This technology became more efficient and convenient for patients because repetitive stem cell injections are possible from one time fat extraction. These studies also showed that the fat-derived stem cells were capable of homing to the site of damage where they were able to suppress the inflammation that was the cause of the pathology and symptoms of these diseases. These patients required less surgeries, transplants and fewer drugs.

Dr. Ra said: “The fact that we showed the way patients can be treated from their own stem cells is very rewarding to me. We are working towards becoming our country’s medical hub for treating autoimmune diseases.”

Engineering Blood Cells to Fight Melanoma


University of California, Los Angeles (UCLA) scientists have successfully completed a proof-of-principle experiment in mice that shows that blood cells can be re-engineered to become melanoma fighting immune cells.

Senior author on this study, Jerome Zack, who is also a scientist with UCLA’s Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, noted that genetic engineering techniques can remodel the blood cells of the mouse so that they form cancer-killing T-cells that seek out the tumor and destroy it. Zack stated: “We knew from previous studies that we could generate engineered T-cells, but would they work to fight cancer in a relevant model of human disease, such as melanoma. We found with this study that they do work in a human model to fight cancer, and it’s a pretty exciting finding.”

White blood cells come in several different varieties, but one group of white blood cells is the “lymphocytes,” which play an exceedingly central role in adaptive immunity. There are two main types of lymphocytes; B-lymphocytes, also known as B-cells and T lymphocytes or T-cells. T-cells receive their name from an organ that sits over the top part of the heart called the thymus. Once T-cells are born, they migrate to the thymus where they undergo a complex maturation process. Once they are released from the thymus into the peripheral circulation, they are ready to serve the immune system. T-cells differ from B-cells in that they possess a surface protein called the “T-cell receptor.” The T-cell receptor recognized foreign substances or “antigens” that are bound to the surfaces of cells. When the T-cell binds to this antigen, it becomes activated and begins to divide and initiates the formation of an immune response against this antigen.

In this experiment, Zack and his co-workers used a T-cell receptor that they had isolated from a cancer patient. This particular T-cell receptor recognized an antigen that is specific to melanomas. The UCLA group then used genetic engineering techniques to place the T-cell receptor gene into the blood-making stem cells in the bone marrow of laboratory mice. After re-introducing these engineered blood-making stem cells into the experimental mice. Next, Zack and his colleagues transplanted a small piece of human thymus into the experimental mice. This gave the mice a place to allow the newly made T-cells to mature.

After approximately six weeks, engineered blood stem cells had formed a large population of mature, melanoma-specific T-cells that were able to target the particular cancer cells. To demonstrate this, the experimental mice were then implanted with two types of melanoma, one that expressed the antigen complex recognized by the T-cell receptor introduced into the bone marrow stem cells, and another tumor that did not. The engineered cells specifically went after the melanoma that expressed the particular antigen, but they left the other tumor alone. Of the nine nude mice used in this study, four animals showed complete elimination of the antigen-expressing melanomas, and the other five showed a marked decrease in the size of the tumors. The immune response against the tumors was determined not only by measuring physical tumor size, but by monitoring the cancer’s metabolic activity using Positron Emission Tomography (PET), which measures how much energy the cancer is “eating” to drive its growth.

Zach noted: “We were very happy to see that four tumors were completely gone and the rest had regressed, both by measuring their size and actually seeing their metabolic activity through PET.” Zack said.

This approach has the advantage of engineering only a few cells that can produce a veritable army of cancer-fighting T-cells. Furthermore, these cells can exist in the circulating blood in low numbers, but if they detect the melanoma antigen, they can replicate and expand their numbers quickly and home to the tumor where they will fight it. Other advantages of this strategy are that the function of the engineered T-cells is not long-lasting in most cases. More engineered T-cells ultimately are needed to sustain a response, but some of these cells will probably become “memory cells.” Memory cells are inactive cells that remember the infection they recently fought, but can be reactivated if they encounter the antigen once again. This suggests that “fresh” cancer-killing cells could be easily generated when needed, perhaps protecting against cancer recurrence later.

The team would like to test this approach in clinical trials. One possible approach would be to engineer both the circulating T-cells and the blood stem cells that give rise to T-cells. The peripheral T-cells would serve as the front line cancer fighters, while the blood stem cells are creating a second wave of warriors to take up the battle as the front line T-cells are losing function. Zack also said that he hopes that this technique could adapted for protocols the battle other cancers like breast and prostate cancers.

Still Unconvinced?


Apparently I’m not the only one who thinks that Geron’s move to table its embryonic stem cell division is solely due to money. See comments by Daniel Salomon, associate professor in the department of molecular and experimental medicine at the Scripps Research Institute in San Diego in a story by ABC News.

Cardiac Stem Cells Replace Heart Muscle In Heart Attack Patients


Two research teams have shown that stem cells harvested from a patient’s own heart can reverse heart attack damage. Roberto Bolli, director of the division of cardiology at the University of Louisville in Louisville, Ky., and colleagues presented their initial results from an ongoing clinical trial at a national meeting.  This trial treated 16 heart attack patients with infusions of cardiac stem cells that had been harvested from their own hearts during bypass surgery. In this experiment, 14 patients had improved cardiac function four months after the procedure, eight of these patients had further improvements a year after infusion, and their heart attack scars shrank.  Data from this clinical trial published in the journal The Lancet.

Director of the Cedars-Sinai Heart Institute in Los Angeles, Eduardo Marbán, discussed final results from a different Phase I clinical trial.  In this second trial, physicians harvested cardiac tissue using a minimally invasive technique, cultivated the stem cells from the cardiac tissue, and then administered them to 17 study subjects. Marbán said that his team’s cells also shrank heart scars, but also caused increases in living heart muscle in the patients (~600 million new heart cells per subject).

The two studies approach the same question; namely the ability of the heart to regenerate using its own stem cell populations. These two studies, however, use distinct approaches to answer this question. Blocked arteries deprive heart muscle, and if the heart muscle cells are kept without sufficient oxygen for a period time, they will start to die, which is the cause of heart attacks. If sufficient numbers of heart muscle cells die, the heart will not be able to service the needs of the body, and the patient will die from heart failure. In the U.S. alone, it is estimated that about six million people have heart failure. These new results provide hope for these patients, many of whom have been waiting for regenerative therapies to mend damaged heart tissue for more than a decade.

Depending on the Food and Drug Administration’s approach to the new therapy, Marbán said, a product based on his team’s work could be available to patients as soon as 2015 or 2016.

It’s All About Money?


According to the Los Angeles Times, Geron abandoned embryonic stem cell research and clinical trials solely of money. Wesley Smith does not believe it for a minute, as he writes in the Weekly Standard. Read them both and decide for yourself.

Having formerly lived in Southern California, I for one do trust the LA Times to get a story straight. Not only that, I simply do not trust the LA Times to put their biases aside and report the facts about a case. I can believe that Geron was strapped for cash, but with the potential for this research and the money-bags at the California Institute for Regenerative Medicine, I find it difficult to believe that private investors were not dumping wads of cash into their laps. I think somethings else is going on and I would love to see the media dig to bottom of it.

Biomaterials to Treat Heart Attacks


A field of experimental, regenerative medicine that has not received much press to date is the field of “biomaterials.” Simply put, bio-materials are organic compounds that can self-assemble and form polymers that reinforce damaged tissues. Such biomaterials are also used to form molds of organs that are seeded with stem cells that form an artificially assembled organ. These stem cells then degrade the biomaterial to leave a newly formed organ. This use of biomaterials is termed “tissue engineering,” and it is one of the most innovative and fascinating new fields of medical research.

Recently, biomaterials have been used to treat the hearts of laboratory animals that have suffered a heart attack, and the results are more than hopeful, even if the biomaterials themselves are not yet ready for human trials.  Furthermore, biomaterials can enhance the healing activities of stem cells.

If biomaterials are used on their own, they can shore up a failing heart. Alginate hydrogels, are based on compounds extracted from brown seaweeds called “alginic acids.”  When crosslinked by positively charged ions like calcium, alginic acids form solid or semi-solid materials.  called a hydrogel.  Injection of alginate hydrogels into the heart muscle after a heart attack increases the thickness of the heart wall and decreases the amount of blood left in the large chambers of the heart after they have been filled with blood (also known as “end diastolic volume” or EDV; see Landa, et al. Circulation 2008; 117: 1388-96, and Leor, et al., J Am Coll Cardiol 2009; 54: 1014-23). In unhealthy hearts, the EDV is high because the heart beats sluggishly and waits longer before each beat. If the EDV goes down after a heart attack, it is usually evidence that the heart has recovered somewhat. Because hydrogels are biodegradable, these positive effects are temporary. For example, polyethylene glycol hydrogels also lower EDV 4 weeks after a heart attack, but this effect goes away after 3 months (Dobner, et al., J Card Fail 2009; 15: 629-36). Therefore, by themselves, biomaterials buy the heart time, but do not promote long-term healing.

In order for biomaterials to work within the heart, they must not activate the immune system to attack them, they must have similar properties to heart muscle, and be liquid at the time of injection into the heart but solid once they achieve their proper location in the heart. Matrigel, for example, was originally extracted from soft tumors, and is composed of several proteins already found in the body (laminin, collagen IV, heparan sulfate proteoglycan, and entactin for those who want to know). Matrigel is liquid at low temperatures but forms a hydrogel at 37 degrees Celsius (our body temperature). Also, because matrigel is made by living cells, is usually imbued with growth factors that can aid the ailing heart and assist the work of implanted stem cells. In fact, experiments with matrigel and embryonic stem cells in mice have shown that matrigel increases the retention of embryonic stem cells that have been injected into the heart after a heart attack and the functional efficiency of the heart compared to injections of just cells (Kofidis, et al., Circulation 2005; 112: I173-7). Matrigel, however, is extracted from mouse tumor cell lines and is not appropriate for use in human patients.

Another potential biomaterial is collagen, which is use to make the scars in the heart after a heart attack. This protein is inexpensive, nontoxic, biodegradable, and friendly to the immune system. Collagen gels have been used to prevent mesenchymal stem cells from redistributing to other organs after they have been injected into the wall of the heart after a heart attack (Dai, et al., Regen Med 2009; 4: 387-95, and Danovic, et al., PloS One 2010; 5: e12077). In large animals, collagen gels have been used to deliver mesenchymal stem cells to precise locations around the heart (Ladage, et al., Gene Therapy 2011; 18(10): 979-85). Tissue engineers have also made vascular beds from collagen gels and “endothelial progenitor cells” or EPCs (stem cells that form blood vessels). Implantation of these engineered tissues into sick rodent hearts improved heart function by increasing blood delivery to heart tissue (Frederick et al., Circulation 2010; 122: S107-17).

Another protein that can potentially serve as a biomaterial for heart attacks is fibrin, which is the material found in blood clots. Fibrin has a major advantage in that it is already recognized by the Food and Drug Administration (FDA) as a product approved for use in human patients. Fibrin can serve as a patch (like a bandage) for hearts, or it can be injected into the heart itself with stem cells. Fibrin acts as a kind of glue that helps retain stem cells in the heart after their delivery (See Breen, O’Brien and Pandit, Tissue Engineer Part B Rev. 2009; 15: 201-14; Terrovitis et al., J Am Coll Cardiol 2009; 54: 1619-26; and Lui, et al., Am J Physiol Heart Circ Physiol 2004; 287: H501-11).

Finally, there are a few artificial biomaterials that are presently being tested. These include self-assembling peptides, PLGA (polylactic-coglycol acid, which is FDA approved), and other similar compounds. These other compounds typically show dosage-dependent toxicities, and some even tend to activate the immune system. Nevertheless, some of these compounds have been used to culture heart muscle cells in the laboratory and others can be injected directly into the heart. Some self-assembling peptides that form protein nanofibers can stimulate the differentiation of bone marrow stem cells into blood vessels (Lin et al., Circulation 2010; 122: S132-41).

Biomaterials have other advantages in that they can bind protein growth factors that promote the survival or even differentiation of implanted stem cells. For this reason, some labs are investigating biomaterials for use in gene therapy.

Biomaterials may provide an adjuvant to stem cell treatments in the heart, and for that reason, biomaterials research deserves more attention than it has been receiving.

Preconditioning Stem Cells from Fat with Viagra Improves their Therapeutic Efficacy


Rackesh Kukreja is professor of internal medicine, biochemistry, and molecular biology, physiology and biophysics, and scientific director of the Virginia Commonwealth University Pauley Heart Center. In his laboratory, Nicholas Hoke and other co-workers have discovered a way to improve the therapeutic capacity of fat-derived mesenchymal stem cells (MSCs).

MSCs from fat can be transformed into heart muscle cells in the laboratory (see Rangappa et al., Ann Thorac Surg. 2003; 75(3):775-9). While these cells will beat in culture, it is unclear if these cells have the calcium ion-handling machinery that allows them to synchronously beat together. When implanted into the hearts of laboratory animals that have suffered heart attacks, stem cells from brown fat shrink the infarcted area and improve the function of the left ventricle. This improvement seems to occur by means of replacing dead heart muscle cells (see Yamada, et al., Biochem Biophys Res Commun. 2006; 342(2):662-70). Several experiments have established that MSCs from fat tissue can improve the function of a rodent’s heart after a heart attack. Sheets of fat-derived MSCS (see Miyahara et al., Nat Med. 2006; 12(4):459-65), cord blood MSCs co-cultured with brown fat stem cells (see Yamada, et al., Biochem Biophys Res Commun. 2007; 353(1):182-8), or even MSCs derived from white adipose tissue (see Schenke-Layland K, et al., J Surg Res; 153(2):217-23; Mazo M, et al., Eur J Heart Fail. 2008; 10(5):454-62; Valina C, et al., Eur Heart J. 2007; 28(21):2667-77) all improved heart function after a heart, the fat-derived MSCs from white fat seemed to do so by enhancing blood vessels formation in the infarcted heart. Other studies showed that white fat derived MSCs did not survive well in the heart after a heart attack (van der Bogt, et al., Transplantation. 2009; 87(5):642-52). Other studies showed that fat-derived MSCs could be converted into heart muscle cells (Gwak, et al., Cell Biochem Funct. 2009; 27(3):148-54), and transplantation of these cells could improve heart function after a heart attack (Okura H, et al., Tissue Eng Part C Methods. 2010; 16(3):417-25). Therefore, fat-derived MSCs have the potential to help an ailing heart, but can we tweek them so that they can survive within the hostile environment of a heart that has just had a heart attack?

Into this gap steps Rackesh Kukreja, Nicholas Hoke and co-workers and their experiments on fat-derived MSCs. They soaked fat-derived MSCs in sildenafil (Viagra) before they transplanted them into rodent hearts after a heart attack. Before you snicker about this, sildenafil is an inhibitor of enzymes called “phosphodiesterases.” Phosphodiesterases degrade signaling molecules like cyclic AMP and cyclic GMP. Both of these molecules are made when cells receive messages from other cells, and the concentration of these molecules inside can determine if a cell survives under certain conditions or dies. Therefore, by treating the cells with sildenafil (Viagra), they increased the intracellular concentration of these signaling molecules.

The results were remarkable. When they injected these preconditioned cells directly into the heart muscle of mice that had experienced a heart attack, the preconditioned cells released more growth factors, survived better than non-conditioned fat-derived MSCs, and also helped repair the heart much more effectively. There was decreased cell death in the hearts treated with the preconditioned MSCs, greater density of new blood vessels, and far less scarring of the heart.
These results demonstrate that preconditioning MSCs from fat with drugs like Viagra is a powerfully simple and novel approach to improve stem cell therapy following a heart attack.

Integrin α6β4 identifies an adult lung stem cell population with regenerative potential


Can damaged lung tissue regenerate? If so, which cells contribute to this regeneration? Can we isolate these regenerative cells and make them available to people with failing lungs?

These are all pointed questions, and associate professor of medicine at the University of San Francisco, Thiennu H. Vu, has published a recent paper in the Journal of Clinical Investigation that partially answers these questions.

The lung consists of a large quantity of tubes that conduct the air to the bloodstream. These tubes, the trachea, bronchi, bronchioles and terminal bronchioles, constitute the “conducting zone” of the lungs. They serve to deliver the air from outside our bodies to the bloodstream. The actual site of gas exchange or “respiratory zone” occurs at the “alveoli.” The terminal bronchioles end in an inflation that resembles a tiny sac. This sac, the alveolus, is very thin; one cell thick.

The cells that compose the alveolus are called alveolar epithelial cells (AECs). There are two types of AECs: flat “type I pneumocytes,” which typically are unable to divide and die off they are damaged by toxins, and “type II pneumocytes,” also known as “great alveolar cells” or “septal cells.”

Type II pneumocytes are usually found near the junctions between alveoli and the septae that separate the alveoli. It is thought that type II cells can divide and replace type I cells if the type I cells are destroyed. Type II cells also secrete large quantities of “surfactant” which is a chemical that keeps the alveolar surfaces from sticking together as they expand and contract. Are type II pneumocytes the primary healing cell in the lung? Vu’s group set out to address this question.

Vu and her co-workers had an indication that mice that lack a particular surface molecule called “integrin beta4” could not repair their lungs after lung damage. Integrins are cell adhesion molecules that help cells stick to the substratum. If we think of lung cells as having a head (the apical surface), and a foot (the basal surface), the foot part of the cell stands on a foundation and this foundation in lungs is something called the “basement membrane.”

Basement membranes are common to other types of cells, but basement membranes in the lung are rich in a protein called “laminin,” and the beta4 integrin, with help from another integrin subunit called alpha6, binds tightly to laminin and keeps the lung cells lock to the foundational basement membrane.

Since the cells that contained alpha6/beta4 on their surfaces seemed to the cells responsible for regenerating the lung after the lung was damaged, Vu and her colleagues stained lung tissue with antibodies against the beta4 integrin. What they discovered surprised them: The beta4-expressing cells did NOT overlap with those cells that made surfactant (type II cells). Furthermore, when they tried to correlate the presence of the beta4 integrin with the available lung cell types (type I AECs, ciliated bronchial cells, type II AECs, and Clara cells), they were not able to show that these beta4 cells corresponded to any known lung cell type.

Next, Vu and others cultured lung cells in artificial media and the beta4 integrin-containing cells grew extremely well, but the other lung cells failed to grow. The growing beta4-positive cells also proved to be a mixed population and had the beta4 integrin in common, but little else.

The next experiment utilized a culture system that Vu’s lab helped develop whereby extirpated lung tissues are used to grow mini-lung-like organs when transplanted into a “nude” mouse (a mouse whose immune system does not work properly). By using a nude mouse, the implanted cells will form the mini-lung without the mouse’s immune system destroying it. By using their mini-lung growing system, Vu and her colleagues were able to grow the mini-lungs effectively if they used whole, macerated lung tissue. The growing lungs went through the various embryonic stages of lung development, thus showing that this assay is an excellent way to study lung development. Next they tried to grow the mini-lungs by using only integrin beta4-containing lung cells plus some embryonic cells. The beta4-positive cells grew into mini-lungs and formed a wide variety of lung-specific cell types. The integrin beta4-containing cells also directed the embryonic epithelial cells to form proper sac-like alveoli. This assay definitively showed that the beta4-positive cells could form type I and type II pneumocytes.

Finally, they injured the lungs of mice with a drug called bleomycin and looked at the cells in the lungs to see if the quantity of beta4-containing cells increased. The results were crystal clear; the beta4-positive cells increased many fold. Then they asked if the type II pneumocytes were dividing in the damaged lungs. They used genetically engineered mice that would express green fluorescent protein in their type II pneumocytes. Then they injured the lungs of these mice and asked if the type II cells increased their numbers. The answer was a clear NO. The regeneration that created new type II pneumocytes created cells that did not express green fluorescent protein, which means that the new type II cells were made from cells that did not originally express green fluorescent protein. Therefore, the beta4-positive cells were the cells regenerating the lung and not the type II cells. The type II cells that were dividing had been derived from the beta4-positive cells.

Vu and her colleagues end this paper with this modest understatement: “Understanding the determinants of β4+ AEC population size and how these cells expand, self-organize, and differentiate along particular lineages should provide further insights into the processes of lung repair, the foundation for better therapeutics.”

I’ll say. If these cells can be found and characterized in humans, they could revolutionize lung treatments. That would be a revolutionary treatment.

Positive Results From Phase 2 Trial Of Mesoblast’s Adult Stem Cell Therapy


Mesoblast announced positive Phase 2 heart failure trial results of its off-the-shelf, adult stem cell product Revascor after all patients had completed a minimum follow-up of 12 months, and a mean follow-up of 22 months. The Phase 2 trial results were presented at the American Heart Association annual meeting in Orlando, Florida, by independent principal investigator Dr Emerson C. Perin, Director of Research in Cardiovascular Medicine and Medical Director, Stem Cell Center, Texas Heart Institute in Houston.

Mesenchymal Precursor Cells or MPCs are bone marrow stem cells that have none of the markers expressed by mature mesenchymal stem cells (MSCs), but they are the stem cells population that gives rise to mesenchymal stem cells. Therefore, they have the advantages of MSCs – such as they are not recognized by the immune system, but because they are not mature MSCs, they can differentiate into a far wider variety of cell types than mature MSCs.

MPC treatment in this trial pooled data from patients that received all different doses and these pooled data showed that patients who had received MPC treatments had a significant reduction in cardiac mortality. Furthermore, at the highest dose, the MPCs completely prevented heart failure hospitalization events. Mesoblast expects that these outcomes will be central to the primary endpoint of a Revascor Phase 3 trial for product regulatory approval by the United States Food and Drug Administration (FDA).

This phase II trial used a randomized, placebo-controlled 60-patient Phase 2 trial that compared the safety and efficacy of three doses of Revascor in addition to maximal approved therapies versus maximal therapies alone in patients with moderate-to-severe congestive heart failure (CHF) defined by New York Heart Association (NYHA) class II or III status and ejection fraction below 40%. The trial enrolled both ischemic and non-ischemic heart failure patients. Heart failure patients with this degree of severity are known to have a high cardiac mortality over a 12-24 month period despite being on maximal approved drug and device therapies.

Treatment with MPCs was well-tolerated. Over a 22-month mean follow-up period, only 1/45 (2%) patients who received a single injection of Revascor died of cardiac causes compared with 3/15 (20%) of the control group (p=0.02). In addition, MPC treatment significantly delayed the time to a first Major Adverse Cardiac Event, MACE, a composite of cardiac death, heart attack or revascularization procedures (p=0.036), and reduced the overall risk for MACE by 78% (p=0.011). Over a mean follow-up of 18 months, 0/15 patients who received the highest dose of MPC (150M) had been hospitalized for heart failure or had died. In contrast, 3/15 (20%) controls and 6/30 (20%) patients who received low (25M) or mid (75M) doses of MPC had either been hospitalized with heart failure or had died. This clinical improvement associated with the 150M dose was accompanied by evidence of cardiac remodeling (reduction in left ventricular end systolic volumes compared with controls at 6 months, p=0.015) and improved functional heart capacity (gain of 52.6 meters over 6 minutes’ walk compared with controls at 12 months, p=0.06).

After 12 months, 40% of all treated patients had reverted to class I NYHA status compared with 14% of all controls, and this effect remained when patients were matched for the presence of class II status at baseline. The group who received the 25M MPC dose showed a significant 8.9 point improvement in ejection fraction over controls at 3 months (p=0.008), with a sustained but less pronounced effect over 12 months. In contrast, the group who received 150M MPC did not show improved ejection fraction, suggesting that the positive effects of this dose on clinical outcomes, remodeling, and functional capacity may be due to other mechanisms such as anti-fibrosis.

Dr. Perin stated: “These clinical findings are the first using any cell therapy in heart failure patients to show a concordant positive effect on clinical outcomes, cardiac remodeling, and functional capacity, the three key parameters in congestive heart failure. Together, they indicate that a single 150 million dose of Revascor may significantly reduce both heart failure hospitalizations and death in these very sick patients who have such a poor prognosis despite maximal existing therapies. Based on their defined product characterization, batch to batch consistency, immediate availability, and lack of clinically relevant immunogenicity, MPCs appear to be an ideal cell type to provide a new level of patient care in congestive heart failure. We look forward to progressing the Revascor clinical program into Phase 3.”

Revascor is being jointly developed by Mesoblast and its strategic alliance partner, Teva Pharmaceutical Industries Ltd. Teva’s Corporate Vice President Global Branded Products, Kevin Buchi, said: “These independently-reviewed results serve to reinforce Teva’s commitment to its strategic investment in Mesoblast’s adult stem cell technology and to our continued support for the clinical development of Revascor.”

Mesoblast Chief Executive, Professor Silviu Itescu, said, “Together with our partners at Teva, we are deeply committed to bringing to market an effective cell therapy product to reduce recurrent hospitalization episodes and risk of death in patients with progressive heart failure. The exciting results presented at the American Heart Association meeting reinforce the strength of our technology and emphasize the need to maintain a rapid development path in order to make this product available for the many patients suffering with heart failure.”

New Heart Cells Increase By 30 Percent After Stem Cell Infusion


Chronic ischemic heart disease results from the partial blockage of blood flow to the heart. It can result in damage to the heart, and symptoms that consist of shooting pain in the chest called “angina.” Fortunately, there are good, animal models of chronic ischemic heart disease and better ways to treat this disease are being investigated. A presentation at the American Heart Association annual meeting has shown that new heart cells can be produced in animals that have been given infusions of stem cells derived from cardiac biopsies or “cardiospheres.”

Research conducted at the University at Buffalo School of Medicine and Biomedical Sciences has demonstrated that the hearts of animals with chronic ischemic heart disease experience a 30 percent increase in healthy heart muscle cells within one month after receiving cardiosphere-derived cells (or CDCs). This finding is contradicts conventional medical wisdom which avers that heart cells are terminally differentiated and thus, are unable to divide.

Ischemic heart disease results from narrowing of coronary arteries and prior heart attacks are the most common cause of heart failure. Other investigators have largely focused on regenerating muscle in scarred tissue, but this UB group has shown that cardiac repair can be achieved by infusing CDCs slowly into coronary arteries of the diseased as well as normal areas of the heart. Study co-author John M. Canty Jr., MD, the Albert and Elizabeth Rekate Professor of Medicine in the UB medical school and UB’s chief of cardiovascular medicine explains: “Whereas most research has focused upon irreversible damage and scarring following a heart attack, we have shown that a single CDC infusion is capable of improving heart function in areas of the heart that are viable but not functioning normally.” Particular areas of heart dysfunction even their there is no fibrotic scarring are common in patients with heart failure from coronary artery disease. Heart failure results from “remodeling” in response to a heart attack, in which the heart enlarges to adjust to the loss of heart muscle. Another consequence of a heart attack and periods of inadequate blood flow to the heart muscle is so-called hibernating myocardium, in which segments of heart muscle exhibit abnormalities of contractile function. Canty commented further: “The rationale for our approach is somewhat analogous to planting seeds in fertile soil versus trying to grow plants in sand.

Gen Suzuki, MD, research assistant professor of medicine in the UB medical school and lead author on the research, noted: “We have shown that cells derived from heart biopsies can be expanded outside of the body and slowly infused back into the coronary arteries of animals with chronic dysfunction from restricted blood flow or hibernating myocardium. The new cardiac muscle cells are small and function more normally than diseased large, hypertrophied myocytes.”

Canty also noted that infusing stem cell formulations directly into coronary arteries also delivers the cells throughout the heart and is much simpler than injecting cells directly into heart muscle which requires equipment that is not widely available.

The research currently is in a preclinical phase but the UB researchers expect that translation to determine effectiveness in patients could take place within two to three years or possibly even sooner.

Stem cell therapy helps kidney transplant patients


Organ transplants usually require transplant patients to take anti-rejection drugs that suppress the immune system of the patients. Transplant patients must take these drugs for the rest of their lives to prevent the patient’s immune system from attacking and damaging the transplanted organ. These anti-rejection drugs, however, have serious side effects. These drugs can prevent the immune system from fighting infections, and this means that viruses can attack the pancreas, thus leading to diabetes, and tumors can pop up without being restricted by the immune system.  Anti-rejection drugs include such drugs as glucocorticoids, cyclophosphamide (very potent), folic acid analogues like methotrexate, purine analogues like azathioprine, and mercaptopurine, cyclosporin, tacrolimus, and sirolimus, and a cytotoxic antibiotic like dactinomycin.

In order to decrease the need for immunosuppressive drugs, a new technique is being developed that adds adult stem cells plus an initial anti-rejection drug treatment seems to allow the immune systems of kidney transplant patients to accept their transplanted organ without the need for lifelong drug therapy.

The procedure goes something like this: First the patient receives the new kidney, followed by a targeted dose of radiation to weaken their immune system and make some room for new immune cells. Next comes a bone marrow transplant from the same donor who donated the kidney. These bone marrow stem cells mix with the patient’s cells and the transplant patient now has an immune system that is a mosaic of their own original immune system and that of the donor’s. This new immune system views the transplanted kidney as a “perfect match.” Thus far, 8 out of 12 patients who have received the new kidney plus the additional bone marrow transplant are progressing without any need for anti-rejection drugs. Adult bone marrow stem cells provide the life-saving support needed for organ transplants.

More on Geron Leaving the Embryonic Stem Cell Business


According to the Washington Post, “Geron Corp., a pioneer in stem cell research that has been testing a spinal cord injury treatment, said late Monday that it’s halting development of its stem cell programs to conserve funds. It is seeking partners to take on the programs’ assets and is laying off much of its staff…In a statement, the company said the decision to narrow its focus “was made after a strategic review of the costs, … timelines and clinical, manufacturing and regulatory complexities associated with the company’s research and clinical-stage assets.”

Bio-ethicist Wesley Smith sees something potentially nefarious at work. Geron was in the midst of a Phase I clinical trial for its embryonic stem cell-derived oligodendrocyte precursor cell line GRNOPC1. Embryonic stem cells (ESCs) are made from human blastocyst-stage embryos. The derivation of ESC lines requires the dis-assembly, and consequent death of the embryo, which is a human person in the very early stages of development. The GRNOPC1 cell line was made from ESC line H1, which was originally made in the laboratory of James Thomson at the University of Wisconsin when he made the first human ESC lines. H1 was originally called WA01.

The cell line GRNOPC1 was made by differentiating H1 cells into oligodendrocyte progenitor cells (OPCs). OPCs are stem cells found in the central nervous system. They divide to form oligodendrocytes, which wrap around the axons of neurons and help them conduct their nerve impulses much faster than they normally would. Because oligodendrocytes take a beating during spinal cord injury, replacing them can potentially help spinal cord injury patients recover some function. Transplanted GRNOPC1 cells have been shown to improve the function of mice that have suffered spinal cord injuries. Geron has also done quite of bit of work to establish that GRNOPC1 cells are safe, at least in mice.

According the Geron’s web site, Geron worked with collaborators at various universities to demonstrate that GRNOPC1 improved movement in spinal cord-injured animals if they were implanted seven days after the spinal cord injury. When Geron scientists examined the spinal cords of the animals that had received the GRNOPC1 cells, they found that the transplanted OPCs had engrafted or became a part of the spinal cord and were functioning as expected. They published these data in May 2005 in the Journal of Neuroscience. Geron and it collaborators also implanted GRNOPC1 cells into spinal cord injured animals nine months after injury. Tissue examinations of these laboratory animals showed that the site of spinal cord injury was filled with GRNOPC1 cells and properly myelinated rat axons that were crossing the lesion. This is something that axons do not do after spinal cord injury, because the inflammation in the spinal cord kills all neurons in the area and axons that traverse the damaged area. Neurons may not be anywhere near the area of spinal cord damage, but if their axons (the portion of the neuron that directs nerve impulses away from the cell body of the neuron) extend through the area, the axons are severed and the neuron retracts its axons. The target that was receiving nerve inputs from the axon now lacks any input from the nervous system and if that target is a skeletal muscle, which is the target for motor neurons, the muscle becomes incapable of contracting.

Geron also notes on its website that all preclinical studies performed in animals provided the rationale for the use of GRNOPC1 in treating spinal injuries in human clinical trials. Extensive safety testing also satisfied the Food and Drug Administration that they were safe for use in humans. The FDA, therefore, gave Geron the green light to test their GRNOPC1 cell line in human patients who had recently suffered spinal cord injuries.

However, Geron is now leaving the very field it pioneered. This is being reported as a calculated business move that is due to the gargantuan financial investment required to bring embryonic stem cells into the world of everyday medicine. Late Monday this week (November 14, 2011), the company said it would cease all studies of stem cell-based treatments for spinal cord injury. This treatment was the first ever embryonic stem cell trial approved in the U.S. Geron, a Menlo Park, California, company has long been viewed as the undisputed leader in stem cell therapies. This leadership role is due to patents Geron holds on technology used to grow, manipulate and inject stem cells into the human body. In fact, Geron helped finance researchers at the University of Wisconsin who first isolated human embryonic stem cells in 1998, allowing the cells to be grown in the laboratory.

Wesley Smith smells a potential rat. He asks the following questions: “That being so, Geron and the media have an obligation to explain the why of this story in some detail and without spin. Was it the recent European ruling banning the patenting of embryonic stem cell products (about which I wrote) a factor? Was its human trial a disappointment? If it is out of money, why aren’t venture capitalists more willing to invest more in the field if it is so promising? I am sure you all have questions of your own.” These are all good questions, but it is entirely possible that Geron, having already sunk 25 million dollars into this venture and seeing that their product was still decades away from coming to the market, they decided to cut their losses and sell it to someone else. Geron has some anti-cancer drugs in the clinical trial pipeline that are doing very well in their clinical trials. These will probably be ready for production long before the stem cell lines are ever ready. Therefore, the financial motive is probably factor. Geron CEO said as much in his statement: “CEO Dr. John Scarlett told investors and analysts Tuesday that focusing on cancer drugs will allow Geron to make more money in a shorter period of time, particularly when “big pharma and big biotech companies are increasingly hungry for first-in-class cancer programs.”

With respect to the poor clinical trials, Geron press releases have revealed no such thing to date. I get Geron’s press releases, and while these are written from a source within the company that has a vested interest in making the news sound good, the phase I trials, for all intents and purposes, seemed to be going well. GRNOPC1 cells were well tolerated, and the Phase I test was meant to only test safety and not efficacy. If there were no improvements in the human patients, it seems premature to suspect that the company bailed on the basis on this one test with four patients. To suspect that the human subject experienced terrible side effects is to accuse Geron of lying, which is improper without better evidence.

Nevertheless, this is a significant story, in that ESCs do not seem to be able to compete with their adult and fetal counterparts at this time. The continued successes of cord blood, bone marrow, and other stem cell treatments are making it harder and harder for ESCs to find a niche in the market. Even in the case of spinal cord injuries, adult stem cells have made progress in helping quadriplegic patients walk with braces. Such news does not make it into the papers as often as it should, but people need to know that killing young human beings is not the most morally acceptable way to make the regenerative cures that we want.

Another factor in Geron’s decision has to be the recent decision of the European Union’s highest court that ESCs and products derived from ESCs are not patentable under applicable EU law. Because Geron probably viewed Europe as potential market for their products, this would have been a huge blow to their future marketing plans. Geron will continue to make innovative medicines, but ESC-derived products, for now, will not be one of them.

Geron Corporation Halts Stem Cell Trial


Geron Corporation is leaving the field that it helped pioneer. It was a calculated business move to sink so much money into embryonic stem cell-derived stem cells. This illustrates the long, expensive path it takes to make stem cell-based products. Late Monday, the company said it would halt its study of a stem cell-based treatment for spinal cord injury, which is the first embryonic stem cell trial approved in the U.S. Now Geron is putting its stem cell division up for sale.

See the rest of the story here.

Stem Cells Repair Lung Damage After Flu Infection


Everyone has struggled with influenza at some point in their lives. This seasonal infection can knock us for a loop and decrease our lung capacity for an inconvenient period of time. How does our body cope with it? In the first place our immune response destroys the influenza virus and the cells infected with it. Secondly, the lung regenerates damaged cells to reclaim the lost lung capacity. Researchers have recently identified and characterized the adult stem cells that can regenerate lung tissue. These findings come from studies of isolated human stem cells, and from parallel studies of mice infected with a particularly nasty strain of H1N1 influenza virus. These findings could potentially be the impetus for new regenerative therapies for acute and chronic airway diseases.

The main authors of this work Frank McKeon of the Genome Institute of Singapore and the Harvard Medical School in Boston, and Wa Xian of the Institute of Medical Biology in Singapore and the Brigham and Women’s Hospital in Boston published this research in the October 28th issue of the prestigious journal Cell.

The H1N1 strain of the influenza virus is as close as you can get to the virus that was responsible for the 1918 influenza pandemic. H1N1 can cause massive lung damage with lots of inflammation and loss of lung tissue. Such infections produce acute respiratory distress syndrome, marked by extensive lung damage and low levels of oxygen in the blood. What hasn’t been clear is what happens to the lungs of those who manage to survive, since two months after the infection, the lungs look normal again in those who survived the infection.

In this paper, studies in influenza-infected mice showed that lungs are capable of true regeneration. Stem cells found along the surfaces of the airways (in the bronchiolar epithelium) proliferate rapidly in mice after viral infection and migrate to sites of damage. Once the stem cells reach the sites of lung damage, they assemble into stem cell “pods” and activate genes that identify them as lung alveoli, which are the small, hollow structures that function as the sites of gas exchange in the lung.

McKeon and Xian were able to clone these same stem cells from human lung tissue. Even if grown in a laboratory culture dish, these lung-specific stem cells show that they can form alveolar-like structures. This is in spite of the fact that these stem cells from the bronchiolar epithelium have a gene expression profile that is very similar to stem cells found in the upper respiratory airways.

This work suggests that airway stem cells are an important and underappreciated ingredient in regenerative medicine. However, in the case of severe, fast-moving infections, the damage to the lungs would overwhelm the regenerative capacity of the lungs. McKeon noted: “The problem in the case of a pandemic is that people die quickly. It is hard to imagine how a cell-based treatment will play in [sic] those time constraints.”

While McKeon is certainly correct, such stem cell-based therapies or secreted factors identified by this study could play an important role in therapies that attempt to enhance the speed of lung regeneration. Such regenerative therapies could aid in those with hard-to-treat condition like pulmonary fibrosis, in which lung tissue becomes scarred. “Pulmonary fibrosis is a bad disease,” McKeon said. “The question is: could you get rid of the fibrosis and replace it with real lung tissue?”

A second study published in the same issue of Cell identifies those molecular pathways in the lung that may also lead to new strategies for encouraging lung regeneration. In that case, researchers led by Shahin Rafii at Weill Cornell Medical College examined mice with one lung removed, a treatment that causes the remaining lung to produce more alveoli.

Pluristem Therapeutics had positive 12-month results from Phase I clinical trials for its PLX stem cells for the treatment of critical limb ischemia


Critical Limb Ischemia or CLI is the culmination of a condition s degenerative disorder called peripheral artery disease (PAD). PAD results from the obstruction of blood vessels, and the most common cases of PAD occur in the blood vessels in the legs. The symptoms are leg pain, difficulty in walking, progressive tissue damage and death, which leads to a need to amputate the limb in order to prevent the onset of gangrene. The best way to treat PAD create new blood vessels that can deliver blood to the tissues of the leg, which will keep the leg tissue alive and prevent cell death and limb degeneration.

To this end, an Israeli stem cell therapy company called “Pluristem” has completed a Phase I clinical trial for its PLX-1 stem cell line as treatment for critical limb ischemia.  This phase 1 trial continued for 12 months and was conducted under protocols approved by the United States Food & Drug Administration (FDA), and the German Paul-Ehrlich-Institute.  In order for such a clinical trial to be considered significant, the treatment must enhance the percentage of patients who survive without suffering amputation of the affected limb.  This endpoint is called the amputation free survival or AFS rate.

Based on the AFS rate after 12 months of treatment, the clinicians involved in the study concluded that PLX-PAD cells seem to provide effective treatment for CLI.  Edwin Horwitz, president of the International Society for Cellular Therapy and chairman of Pluristem’s Scientific Advisory Board, stated: “AFS is the single most important endpoint in CLI clinical trials… Even though these Phase I trials were not controlled studies, the data collected in these trials on AFS indicate significant potential for PLX-PAD cells in treating CLI patients.” Because Phase I studies are designed to test the safety of the treatment, they cannot be used to determine the efficacy of the treatment.  The PLX-1 cells are definitely safe for human patients, since the study met all endpoints and did not have to be stopped because of unforeseen side effects.  Therefore, Pluristem will almost certainly be allowed to conduct Phase II studies with PLX-1 cells, which are designed to determine the efficacy of treatments.

PLX-1 cells are derived from human placenta.  Human placenta contains a wealth of stem cells, and one of the stem cell populations in human placenta is a mesenchymal stem cell that can form blood vessels and stimulate the regenerative effects of other stem cells.  These particular mesenchymal stem cells derived from placenta can potentially enhance the capabilities of umbilical blood-making stem cells when such cells are used to reconstitute the bone marrow of human patients (see Prather, Toren, Meiron, Expert Opin Biol Ther.2008;8(8):1241-50).  Furthermore, these same PLX-1 cells restore blood flow in laboratory animals that suffer from CLI (Prather, et al., Cytotherapy. 2009;11(4):427-34).

Since the only present cure for CLI is amputation of the affected limb, regenerative treatments like PLX-1 are a welcome site for those who suffer from Peripheral Artery Disease.

Using Induced Pluripotent Stem Cells to Model Mental Diseases in a Dish


The brains of patients who suffer from neurological disorders like autism or schizophrenia work differently than those who do not have such conditions. The precise functional differences in the neurons of those who suffer from such conditions are not completely understood, but stem cell technology has provided a way to study this very question. Scientists have literally been able to “turn back the clock” on the neurons of schizophrenic patients and see some of the abnormalities they display during development.

Researchers isolated skin cells from schizophrenia patients and converted the skin cells into induced pluripotent skins cells (iPSCs) by utilizing using genetic engineering technologies. They then treated these iPSCs with various growth factors to reprogram them into neurons, which are the cells in the central and peripheral nervous systems that generate nerve impulses and are responsible for thinking, reasoning, emotion, and other basic and higher brain functions. Once they made the cultured neurons, they subjected them to various physiological tests and measured the ability of neurons made from the iPSCs derived from patients with schizophrenia, and compared them to neurons made by the same protocol from patients who do not suffer from schizophrenia. The results were telling.

Neurons made from iPSCs derived from skin cells from schizophrenia patients looked normal, but the connections they made with other neurons were abnormal. Neurons connect with each other through special connections called “synapses.” Synapses consist of the end of the neuron, which is called the “axon terminus,” and the cell that receives the neural impulse from the signaling neuron. Neurons can give their input to the front part of another neuron, or they can give their input to other parts of a neuron. Synapses consist of a host of special proteins that dock the neurons together and facilitate the reception of signals from one neuron to another. Defects in synapses lead to abnormalities in nerve impulse conduction, and the neurons from schizophrenic patients showed structural abnormalities in the synapses that they made with other neurons and also produced fewer synapses with other neurons in general.

If that was not enough, Gage and his co-workers went the next step. They treated these cultured neurons with drugs that are normally used to treat schizophrenia. These drugs reversed the abnormalities found in the cultured neurons. This completely contradicts some of the current thinking regarding the treatment of schizophrenia, which asserts that by regulating the amount of particular neurotransmitters like dopamine and serotonin, psychiatrists can ameliorate the symptoms of schizophrenia. Now it appears that the drugs actually induce structural changes in the neurons and the synaptic junctions they make with other neurons and this is the reason these drugs mitigate schizophrenia symptoms.

Lead researcher, Fred (Rusty) Gage, professor of genetics at the Salk Institute for Biological Studies and a member of the executive committee of the Kavli Institute for Brain and Mind (KIBM) at the University of California, San Diego, said: “This allows us to identify subtle changes in the functioning of neuronal circuits that we never had access to before.” Gage continued: “As we accumulate models for these diseases – bipolar disease, schizophrenia, depression, autism – we are going to be able to explore if there are really differences between them that exist on a cellular or gene expression level.” — Fred Gage

Gage also noted that the need to induce structural changes in the neurons in order to assuage the symptoms of schizophrenia might explain why schizophrenia drugs take time before they actually help the patient. In fact, this might explain why other psychoactive drugs take so long to work as well. For example, if depression was simply a matter of modulating the concentration of a particular neurotransmitter, then an anti-depressant should have immediate effects. However, such drugs like antidepressants often take weeks to work. Could it be that such medications work at the structural level and not only at the neurotransmitter level?

When asked what technological advances are needed to explore this further, Gage responded: “One limitation is we haven’t differentiated the cells into specific cell types—neuronal subtypes. Right now we’re just laying these neurons down and allowing them to form connections as they might. Looking ahead, it’s going to be important for us to differentiate the cells. For example, to differentiate and model the cortical neurons, which are responsible for thinking tasks, or the hippocampal neurons, which are responsible for memory tasks. I can one day see us using microfluidic chambers to achieve this. They will allow us to compartmentalize microscopically specific subtypes of neurons in certain locations, and then regulate how they connect to each other. That way you can simulate in a more accurate manner how these subtypes connect with each other in the brain. The future of this is really exciting because the dish is going to get much more complicated.”

Regenexx Corporation uses stem cells to help young woman with lower back pain


Regenexx Corporation in Broomfield, CO specializes in using a patient’s own stem cells to treat joint problems. They have treated arthritic knees, shoulders, and backs with their on-site bone marrow stem cell processing procedure. By transplanting the expanded stem cells from a patient into the joint, patients can experience relief of symptoms and structural improvement of the affected joint.

Regenexx has just announced that a 36-year old woman who suffered from significant back pain for two and a half years was treated by the Regenexx procedure. She had tried physical therapy, IDET (a procedure where a catheter is inserted in the low back disc to burn away painful nerves), epidural steroid injections, facet injections, and trigger point injections, but her pain did not abate. Her MRI showed reactive bone swelling in the vertebrae with compression of the left S1 nerve root. Regenexx physicians had her own specially cultured stem cells were injected into the L5-S1 lower back disc using the Regenexx-C technique.

Her response was telling.  When asked how she felt now as opposed to before the procedure, she said that she felt “Good,” and had experienced “noticeable improvement.” She now only has mild pain, and her range of motion has increased. She can do more since the procedure, and she wrote: ”Much more active and back to a normal life!”

She had failed about every existing conservative low back injection therapy and surgery, but she responded well to the injection of her own specially cultured stem cells into the L5-S1 disc. Regenexx scientists cautiously noted that not every patient achieve these same results, but they were able to help this young lady return to a more active lifestyle.

Umbilical Cord Blood Stem Cells and Spinal Cord injury


In a previous post we discussed statements stem cell scientist Alan Trounson about the use of bone marrow-derived mesenchymal stem cells as a treatment for spinal cord injuries.  In this post, we will examine other statements he makes about umbilical cord stem cells as treatments for spinal cord injury.

Trounson also writes earlier in the same article: “Studies involving umbilical cord blood for neurological indications have been promoted as a result of preclinical data on the apparent formation of neurons in vitro but there is little evidence of their transdifferentiation to functional neurons or glial cells in vivo.”

This statement, like the one about bone marrow-derived mesenchymal stem cells, is misleading.  First of all, umbilical cord blood contains a wide variety of cell types and stem cells.  There is a blood-making stem cell in cord blood, and there are also mesenchymal stem cells, unrestricted somatic cells, and neural stem cells.  Furthermore, there is no evidence that embryonic stem cells form neurons in the spinal cord of human patients either.  Therefore, Trounson is setting a standard for umbilical stem cells that even embryonic stem cells cannot yet meet.  The real question is does administration of umbilical cord stem cells help patients with neurological conditions.

Can umbilical cord stem cells form neurons in culture?  The answer is a clear yes.  Buzanska and colleagues established the existence of a neural stem cell population in umbilical cord blood.  They expanded a population of neural stem/progenitor cells selected from the non-blood-making fraction of umbilical cord blood.  From this fraction, they established a human umbilical cord blood neural stem-like cell (HUCB-NSC) line.  They treated the cells with serum and a chemical called dBcAMP to make them form neurons.  Upon treatments, the HUCB-NSC cells expressed many functional proteins for a variety of different types of neurons, and also showed the types electrophysiological characteristics of neurons.   This definitively showed that cord blood-derived progenitors could be effectively differentiated into functional neuron-like cells in vitro  (Buzanska et al., Neurodegener Dis. 2006;3(1-2):19-26).

Buzanska’s data is significant because most of the time when umbilical cord blood stem cells are used in experiments, a mixed population is used that consists of a few neural-progenitor cells and many other type of progenitor cells.  Therefore, the failure of umbilical cord stem cells to form neuron in vivo is not an indication of the failure of the specific neural progenitor population to form neurons.  Rather it is an indication that the small population of neural progenitor cells was unable to form enough detectable neurons for the experiment in question.

Secondly, Trounson states that there is little evidence of the differentiation of cells to neurons or glia in vivo.  However, an experiment by Lim and his colleagues have shown that this is not the case.  Lim and coworkers administered human umbilical cord mesenchymal stem cells (MSCs) into the spinal cord by means of lumbar puncture and intravenously into the tail vein of rats that had suffered a stroke.  The cells were transplanted 3 days after the stroke, and the rats were tested one week, two weeks, three weeks, and four weeks after the stroke.  Rat brains were also examined one week after the administration of the umbilical cord stem cells.  That rats that had received hUCB-MSCs by means of lumbar puncture had significantly more cells in the damaged areas of the brain than those rats that had received cells intravenously.  Also, many of the cells administered by means of lumbar puncture expressed genes specific to neurons and astrocytes.  Animals that received hUCB-MSCs also showed significantly improved motor function and reduced ischemic damage when compared with untreated control animals.  This is good evidence that umbilical stem cells can form neurons in vivo, which is in direct contradiction to Trounson’s assertion (Lim JY, et al., Stem Cell Res Ther. 2011 Sep 22;2(5):38).

Additionally, administration of umbilical cord cells can help patients with neurological diseases even though they may not differentiate into neurons in the spinal cords of patients.  For instance, several stroke patients have shown improvement after administration of umbilical cord stem cells (Harris DT, Stem Cell Rev. 2008 Dec;4(4):269-74).  Therefore, umbilical cord stem cells have therapeutic potential for neurological conditions, that is, as yet, untapped, and deprecating them does patients no good at all.

Remember that Trounson is receiving lots of taxpayer money for his California Stem Cell Institute.  This institute is pushing embryo-destructive research on the public by using taxpayer dollars.  Therefore, it is necessary for him to make somatic stem cells look as paltry as possible and push embryonic stem cells into as positive light as possible,  However, the huge amount of money simply cannot be justified and neither can the wanton destruction of human life.  Trounson has overstated the vase of embryonic stem cells and understated the case for adult and umbilical stem cells.  It is simple politics and not science.