Embryonic Stem Cell Therapy,EmCell

The Shady Side of
Embrionale Terapia con cellule staminali

Stephen Barrett, M.D.

Terapia con cellule staminali is certainly a promising area for research. Stem cells have the ability to give rise to many specialized cells in an organism. Certain types of stem cells are already used to restore blood-forming and immune system function after high-dose chemotherapy for some types of cancer, and several other restorative uses have been demonstrated. The broadest potential application is the generation of cells and tissues that could be used to repair or replace damaged organs. If scientists can learn how to control stem cell conversion into new, functionally mature cells, doctors might be able to cure many diseases for which therapy is currently inadequate [1,2]. Tuttavia, the claims made by commercial promoters go way beyond what is now likely and should be regarded with extreme skepticism. The main commercial sources have included Embryonic Tissues Center in the Ukraine; Stem Cell of America (formerly called Medra, Inc) in Mexico; the Brain Therapeutics Medical Clinic (formerly called the Health Restoration Medical Center and the Brain Cell Therapeutic Clinic) in Mission Viejo, California; IL Vita Nova Clinic in Barbados; and the Beijing Xishan Institute for Neuroregeneration and Functional Recovery in Beijing, Cina.

The Embryonic Tissues CenterEmCell

The Embryonic Tissues Center (EmCell) appears to be the oldest commercial source of embryonic terapia con cellule staminali. Its proprietors, Alexander Smikodub, MD, Ph.D., and Alexey Karpenko, MD, Ph.D., are described as professors at National Medical University. The EmCell Web site claims:

Scientists at the center have been doing embryonic stem cell transplantation for 13 anni, have performed 2,000 transplants, and have “the worlds largest clinical experience . . . in various diseases and conditions.” [3]
Smikodub was the “first in the world to introduce schemes of treatment of many diseases of internal illnesses . . . involving embryonic cell suspensions of mesenchymal, ectodermal, and endodermal origin.” [3]
The cells used at the the clinic “do not possess antigenic properties, making rejection impossible.” [5]
No negative side effects were observed [4].
“Curative effects of Embryonic Stem Cell Transplantation in numerous diseases are far beyond the possibilities of any other modern method.” [6]
Shortly after transplantation, patients experience “increased vigor, improved feeling of inner strength, belief in favorable result in treatment, absence of depression, improvement of mood and mental creativity.” [7]
“Restored functional activity of impaired and damaged internal organs and tissues leads to steady recovery.” [7]
The treatment has achieved “positive results” in cancer, AIDS, diabete, sclerosi multipla, Morbo di Crohn, and more than 50 other diseases and conditions [8].
Cell therapy contributes to “antitumoral immunity” and can be used to prevent disease as well as relapses and metastases [9].
How credible are these claims? How are the cells prepared? Are steps taken to ensure that they are not infectious? How was it determined that patients have no side effects? Does the clinic follow its patients and keep score? Have enough cancer patients to determine 5-year survival rates? Have Smikodub and Karpenko published their results? Do their theories and methodology make sense?

The ALS Therapy Development Foundation has been monitoring claims that fetal stem cell infusions might be effective against amyotropic lateral sclerosis (Lou Gehrig’s disease). Its Web site states that two American physicians (Mitchell Ghen, D.O., and Dan Cosgrove, MD) have treated patients in a “new and untested way,” but so far no conclusions could be drawn about effectiveness. Foundation documents also note that (UN) some patients have experienced flu-like symptoms, (B) three patients have had dark-colored urine that may signify hemolytic anemia and/or kidney damage, E (C) it is not clear whether the cellule staminali are actually surviving long enough to have an effect [10,11]. In March 2003, the FDA seized records at Ghen’s clinic and Cosgrove said he had stopped offering the treatment [12]. Cryobanks International, which had supplied the cells to Ghen and Cosgrove, stopped doing so after the FDA contacted them [13].

IL ALS Foundation has also investigated the Cell Therapy Clinic by talking with a staff physician, sending a detailed follow-up questionnaire, and talking with several former patients. The Foundation’s report states:

EmCell did not answer many of the questions, and in some areas refused to elaborate on important details such as their method for screening against the AIDS or hepatitis viruses in the cells or their method of cell extraction.
We also asked . . . questions that focused on how they were able to report on patients who have benefited from the treatment. They were not willing to explain their conclusions or how they reached them.
We have not found any data that suggests that the methodology used by EmCell is scientifically reasonable, or that it is helping ALS patients. Although the Foundation has not received any reports of ALS patients being harmed by EmCell, the Foundation has not received any verifiable reports of improvement following EmCell treatment either.
Terapia con cellule staminali is being pursued by a number of credible institutions around the world and ALS-TDF is working with many of the leaders in that area. EmCell’s $15,000 terapia con cellule staminali bears very little resemblance to what is currently being done in leading institutions around the world.
One of the main elements that makes EmCell’s approach different from these leading institutions is their method of delivery. EmCell is injecting fetal stem cells into the abdomen and veins of patients. This approach is similar to the therapy that has been offered in Mexico, in which they have been using bovine stem cells as a cell source. Tuttavia, those who visited these Mexican clinics have not shown any measurable benefit that we know of to date.
EmCell suggested to us that the number of cells does not matter since the cells will divide once they are in the body. If EmCell believes this is true, this raises a significant red flag since the effect of every credible terapia con cellule staminali tried to date has been, in part, dependent on the number of cells injected. Dose does matter, and it indicates there is a lack of understanding on the part of EmCell about how stem cells work.
EmCell suggests that these stem cells DO NOT draw the attention of the immune system. This is another red flag. It is well known that the immune system will generally eliminate any foreign cell, especially in the peripheral system where EmCell is transplanting the cells. Newly injected cells are very unlikely to live very long without some form of immune suppression. In current US stem cell experiments, immunosuppressive drugs are generally used.
Most scientists . . . do not believe it’s plausible to inject a limited number of cells into the abdomen and have them travel into the brain in any way that would help in ALS.
EmCell does not appear to have any real tracking mechanism in place to identify improvements and declines in their patients after they have returned home. After talking with several patients who visited the clinic, it is clear that no evaluation was made of their physical or neurological condition. It is suspicious that they are making claims of improvement for an entire group of people that were not followed in a manner that could generate any viable claims [14].
In August 2003, I did Medline searches to see whether Smikodub or Karpenko had published any reports about their patients in peer-reviewed medical journals. I found none that appeared relevant to the curative claims described above.

Stem Cell of America (formerly called Medra, Inc.)

The chief American commercializer of embryonic terapia con cellule staminali is William C. Rader, MD, a psychiatrist in Malibu, California, who used to run Rader Institute clinics that specialized in treating eating disorders. For $25,000 (wired in advance), Rader will arrange for treatment at his Mexican clinic. In the past, he has also done business under the names Mediquest Ltd., Czech Foundation, Dulcinea Institute, Ltd., and Medra, Inc. A message posted to the Yahoo StemCells group indicates that before he opened his own clinic (In 1997 in the Bahamas), Rader escorted patients to the Ukraine clinic. Like EmCell, Rader has claimed that his fetal trattamento con cellule staminali is not antigenic and has no side effects. In a 1997 document, he stated:

Because fetal cells uniquely do not have antigenicity, they can be given to anyone with no reaction, no rejection, immunusuppressive drug therapy, or any side effects whatsoever. When a patient receives fetal fresh cell therapy (usually given intravenously over a few hours. . . ), the first action of cells is to stimulate the cells already present in the recipient’s system, making them more potent. Then they actually replace the recipient’s immune cells and, eventually engraft, which means they actually continually grow more fetal cells, resulting in a new and stronger immune system [15].

With respect to cancer, Rader has claimed that his treatment enables chemotherapy and radiation to continue longer and virtually eliminate their side effects [15]. Medra’s “Factsheet” claimed:

The fetal stem cell searches out, detects and then attempts to repair any damage or deficit discovered, as well as releases growth factors, which stimulate the body’s own repair mechanisms. . . .

A partial list of diseases includes:

Alzheimers, Anemia, Autismo, Brain damage, Cancer, Cerebral Palsy, Sindrome dell'affaticamento cronico, Depressione, Diabete, Diverticolite, Epilessia, Impotence, Immune Suppression, Leucemia, Sclerosi multipla, Parkinsons, Artrite reumatoide, Sickle Cell Anemia, Spinal Cord Injury, Colpo, Systemic Lupus Erythematosus and Ulcerative Colitis. . . .

Rarely has a single treatment modality offered so much promise to those suffering from some of mankind’s worst afflictions [16].

Rader has also claimed that by “strengthening the immune system, fetal cells offer prevention from acquiring multiple diseases, including cancer, where the fetal cells actually form an anti-cancer barrier which becomes another anti-aging factor.” [13] I don’t believe that. In order to substantiate such claims, thousands of people would have to be followed in a controlled trial that lasted many years. Stem cell technology has not existed long enough for any such study to have been done.

Medra, Inc.’s “Factsheet” identified Rader as medical director and “il prof. Albert Scheller, MD, Ph.D.” as “chief scientific investigator.” Searching Medline, I found no publications one by either of them that are relevant to the claims they made for Medra’s treatment. In 2011, Medra changed its name to Stem Cell of America and Rader’s clinic was moved from the Dominican Republic to Mexico. In 2014, the Medical Board of California revokjed Rader’s medical license. During the proceedings, the board concluded that many of the claims Rader had made in his book, Blocked in the U.S.A, were false [17].

Beijing Xishan Institute for Neuroregeneration and Functional Recovery

The Beijing Xishan Institute for Neuroregeneration and Functional Recovery in Beijing, Cina, is offering stem cell treatment for spinal cord injury, amyotrophic lateral sclerosis Alzheimers disease, paralisi cerebrale, colpo, Parkinsons disease and other neurodegenerative conditions. Its founder/director, Dott. Hongyun Huang, is a neurosurgeon who did research on the biology of fetal cells at Rutgers University and New York University before returning to China. Huang says he injects patients with olfactory sheathing cells (OSCs) obtained from aborted fetuses. The Institute is reported to have treated hundreds of patients and to have thousands of people on its waiting list. The cost is reported to be over $20,000 [18]. In 2003 Huang reported his experience with 171 patients and claimed that OEC transplantation can improve the neurological function of spinal cord of spinal cord injury patients regardless of their age [18]. Tuttavia, his report contains no raw data, provides few details of the patients’ functional ability, did not compare the patients to untreated patients, and limited the patient evaluations to only 2 A 8 weeks after the operation. In 2006, the journal Neurorehabilitation and Neural Repair published a detailed report on his results with seven patients whom the authors examined before and one or more times within a year after Huang’s treatment. The authors concluded: (UN) five of the seven patients had significant complications (three had meningitis), (B) none of the patients showed objective evidence of improvement, E (C) unless Huang conducts a proper study, patients would be ill-advised to undergo his treatment [20]. A report in the Boston Globe noted that Huang’s website includes profiles of patients he has treated for a wide variety of conditions with different causes and different symptoms, yet Huang treats them all with the same cells [18].

Other Clinics

At least two other clinics have advertised trattamento con cellule staminali. The Brain Therapeutics Medical Clinic is run by David Steenblock, D.O., who claims to have “put together a number of growth factors and natural products that are known to promote and protect new brain cells” and calls terapia con cellule staminali UN “new and exciting treatment for brain regeneration.” The clinic’s Web site states that Steenblock “has devoted many years to research in the fields of biochemistry, pathology, nerve and muscle physiology, cardiovascular disease and other diseases of aging.” Yet a Medline search shows that his only mainstream journal publications were three co-authored articles about clotting factors in dogs and guinea pigsall published in the late 1960s when he worked as a laboratory research assistant during his osteopathic training. In 1994, after being charged with negligently treating two patients, Steenblock signed a stipulation under which he admitted failing to adequately document their management and had failed to issue a warning about possible side effects of an injection he had administered to one of them. He was assessed $10,000 and placed oin five years’ probation under which he was required to take extra continuing education courses in pharmacology, medical charting, and ethics [21]. In 1995, after the door to his hyperbaric oxygen chamber blew out (injuring three persons), investigators noted that he was using three unlicensed persons as “physical therapy assistants.” [Subsequent charges that he had violated his probation resulted in extending his probation for another three months and assessment of another $3,500 in costs [22].

The Vita Nova Clinic offers terapia con cellule staminali designed and administered by Professor Yuliy V. Baltaytis, MD, Dottorato di ricerca, DSc. The Vita Nova site claims that Baltaytis has written six books and over 200 scientific articles and has successfully treated patients with arthritis, Alzheimer, cancro, diabete, leucemia, and many other conditions. Tuttavia, he has no publications indexed in Medline and is not mentioned on any other Web site (which I would expect if he had significant scientific standing). I see no more reason to trust him or Steenblock than there is to trust the others mentioned above.

In 2009, a team of Israeli scientists reported that a teenage boy had developed tumors of his brain and spine four years after beginning trattamento con cellule staminali at a Russian clinic. The tumors appear to have been derived from the transplanted stem cells. The boy has a rare neurological disease that local doctors say could not have been helped by stem-cell therapy [23].

Cord Blood Banking

The Cord Blood Registry (Cbr), headquartered in San Bruno, California. provides processing and storage of stem cells from umbilical cord blood for potential future use by the child or family members. In 2010, its fees were $2,195 initially and $125 per year for storage after the first year. Cryobanks International, located in Alamonte Springs, Florida, offers what appears to be similar services. Its 2010 fees were $1,399 for the first year and $120 per year after that, with discounts available for long-term prepayment.

Cbr’s Web site states that stem cells are being used to treat a variety of cancers and blood disorders and that research shows possible value against Alzheimer’s disease, Morbo di Parkinson, e malattie cardiache. It also states that, “Saving your baby’s cord blood . . . can be lifesaving to your family.” [24] Tuttavia, The American Academy of Pediatrics (AAP) states there is no strong evidence to recommend routine cord blood banking for an infant’s future use. It’s 2007 position statement on that subject states:

No accurate estimates exist of the likelihood of children to need their own stored cells. The range of available estimates is from 1 In 1,000 to more than 1 In 200,000. For this and other reasons, it is difficult to recommend that parents store their children’s cord blood for future use.
Given the difficulty in estimating the need for using one’s own cord blood cells for transplantation, private storage of cord blood as “biological insurance” is unwise. Tuttavia, banking should be considered if there is a family member with a current or potential need to undergo a stem cell transplantation. Per esempio, conditions such as leukemia or severe hemoglobinopathy may indicate the need for directed-donor cord blood banking for sibling cord blood transplantation [25].
Others have noted that people who receive their own stem cells might be prone to repeat the same disease. In March 2004, The Medical Letter concluded: “At the present time, private storage of umbilical cord blood is unlikely to be worthwhile. Parents should be encouraged to contribute, when they can, to public cord banks instead.” [26]

The Bottom Line

Although terapia con cellule staminali has a few practical applications and considerable promise, there is no reason to believe that EmCell, Medra, IL Brain Therapeutics Medical Clinic, Vita Nova, the Beijing Xishan Institute for Neuroregeneration and Functional Recovery, or any other commercial stem-cell clinic are providing it as a legitimate service. Their theories and methods are simplistic; their treatments may have adverse effects; they offer no credible outcome data; and their promises go far beyond what is now possible.

Cord blood banking has some legitimate uses but appears to be a poor investment except for people who (UN) have a relative with a disease for which cord blood effectiveness has been demonstrated or (B) are wealthy enough to afford betting more than $3,000 on a long shot.
References

Stem cell basics. NIH Web site, accessed September 24. 2009.
What would you hope to achieve from human pluripotent stem cell research? National Institute of Health Web site, aprile 26, 2000.
Embryonic stem cell transplantation: 13 years of clinical experience. EmCell Web site, accessed June 19, 2006.
Historical background of embryonic stem cell transplantation. EmCell Web site, accessed June 19, 2006.
Features of embryonic stem cell transplantation. EmCell Web site, accessed accessed June 19, 2006.
Major curative effects of embryonic stem cell transplantation. EmCell Web site, accessed accessed June 19, 2006.
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Experience in treatment of oncology patients. EmCell Web site, accessed accessed June 19, 2006.
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What’s happening with cord blood. ALS-TDF Web site, Dec 2002.
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Fetal terapia con cellule staminali factsheet. Maggio 2004.
Decision after non-adoption. In the matter iof the accusation against William C. Rader, M.D. Medical Board of California Case No. 20-2010-205857, Oct 6, 2014.
Cook G. Chinese surgeon’s claims about cell implants disputed. Boston Globe, Giugno 19, 2006.
Huang H and others. Influence of patients’ age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury. Chinese Medical Journal 116:1488-1491, 2003.
Dobkin BH and others. Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury. Neurorehabilitation and Neural Repair 20:5-13, 2006.
Barrett S. Regulatory action against David Steenblock, D.O. (1993-1994) Quackwatch, Marzo 31, 2004.
Barrett S. Regulatory action against David Steenblock, D.O. (1997-2000). Quackwatch. Marzo 31, 2004.
Amariglio N and others. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 6(2): e1000029. doi:10.1371/journal. pmed.1000029.
CBR home page, accessed Sept 9, 2010.
Policy Statement: Cord blood banking for potential future transplantation. Pediatrics 119:165-170, 2007.
Private cord blood banks. The Medical Letter 46:21-22, 2004.
This article was revised on April 5, 2015.