Terapia con cellule staminali embrionali, EmCell

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Terapia con cellule staminali embrionali

Stefano Barrett, MD.

Stem cell therapy is certainly a promising area for research. Le cellule staminali hanno la capacità di dare origine a molte cellule specializzate in un organismo. Alcuni tipi di cellule staminali sono già utilizzati per ripristinare la funzione della formazione del sangue e del sistema immunitario dopo la chemioterapia ad alte dosi per alcuni tipi di cancro, e sono stati dimostrati molti altri usi riparativi. L’applicazione potenziale più ampia è la generazione di cellule e tessuti che potrebbero essere utilizzati per riparare o sostituire organi danneggiati. Se gli scienziati riuscissero a imparare come controllare la conversione delle cellule staminali in nuove, cellule funzionalmente mature, i medici potrebbero essere in grado di curare molte malattie per le quali la terapia è attualmente inadeguata [1,2]. Tuttavia, le affermazioni avanzate dai promotori commerciali vanno ben oltre ciò che è ora probabile e dovrebbero essere considerate con estremo scetticismo. Le principali fonti commerciali hanno incluso Embryonic Centro Tessuti in Ucraina; Cellule staminali d'America (precedentemente chiamato Medra, Inc) in Messico; la clinica medica di terapia del cervello (precedentemente chiamato Centro medico per il ripristino della salute e Clinica terapeutica delle cellule cerebrali) a Missione Viejo, California; IL Clinica Vita Nova alle Barbados; e l'Istituto Xishan di Pechino per la neurorigenerazione e il recupero funzionale a Pechino, Cina.

Il Centro dei tessuti embrionaliEmCell

Il Centro dei tessuti embrionali (EmCell) appears to be the oldest commercial source of embryonic stem cell therapy. I suoi proprietari, Alexander Smikodub, MD, Dottorato di ricerca, e Alexey Karpenko, MD, Dottorato di ricerca, sono descritti come professori presso la National Medical University. Il sito Web EmCell afferma:

Gli scienziati del centro hanno effettuato trapianti di cellule staminali embrionali 13 anni, hanno eseguito 2,000 trapianti, e avere “la più grande esperienza clinica al mondo . . . in varie malattie e condizioni.” [3]
Smikodub era il “primo al mondo a introdurre schemi di trattamento di molte malattie di malattie interne . . . che coinvolgono sospensioni cellulari embrionali di mesenchima, ectodermico, e origine endodermica.” [3]
Le cellule utilizzate nella clinica “non possiedono proprietà antigeniche, rendendo impossibile il rifiuto.” [5]
Non sono stati osservati effetti collaterali negativi [4].
“Gli effetti curativi del trapianto di cellule staminali embrionali in numerose malattie vanno ben oltre le possibilità di qualsiasi altro metodo moderno.” [6]
Poco dopo il trapianto, esperienza dei pazienti “aumento del vigore, miglioramento della sensazione di forza interiore, fiducia nel risultato favorevole del trattamento, assenza di depressione, miglioramento dell’umore e della creatività mentale.” [7]
“L'attività funzionale ripristinata degli organi e dei tessuti interni compromessi e danneggiati porta ad un recupero costante.” [7]
Il trattamento ha raggiunto “risultati positivi” nel cancro, AIDS, diabete, sclerosi multipla, La malattia di Crohn, e più di 50 altre malattie e condizioni [8].
La terapia cellulare contribuisce a “immunità antitumorale” e può essere utilizzato per prevenire malattie, ricadute e metastasi [9].
Quanto sono credibili queste affermazioni? Come vengono preparate le cellule? Vengono adottate misure per garantire che non siano infettive? Come è stato stabilito che i pazienti non hanno effetti collaterali? La clinica segue i suoi pazienti e tiene il punteggio? Avere abbastanza pazienti affetti da cancro per determinare i tassi di sopravvivenza a 5 anni? Chiedi a Smikodub e Karpenko di pubblicare i loro risultati? Le loro teorie e la loro metodologia hanno senso?

La Fondazione per lo sviluppo della terapia ALS ha monitorato le affermazioni secondo cui le infusioni di cellule staminali fetali potrebbero essere efficaci contro la sclerosi laterale amiotropa (La malattia di Lou Gehrig). Il suo sito Web afferma che due medici americani (Mitchell Ghen, FARE., e Dan Cosgrove, MD) hanno trattato pazienti in a “modo nuovo e non testato,” ma finora non è stato possibile trarre conclusioni sull'efficacia. Anche i documenti della Fondazione lo notano (UN) alcuni pazienti hanno manifestato sintomi simil-influenzali, (B) tre pazienti hanno avuto urine di colore scuro che potrebbero indicare anemia emolitica e/o danno renale, E (C) non è chiaro se il cellule staminali in realtà sopravvivono abbastanza a lungo da avere un effetto [10,11]. A marzo 2003, la FDA sequestrò i documenti della clinica di Ghen e Cosgrove disse che aveva smesso di offrire il trattamento [12]. Criobanche internazionali, che aveva fornito le celle a Ghen e 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, o che aiuta i pazienti affetti da SLA. Sebbene la Fondazione non abbia ricevuto alcuna segnalazione di pazienti affetti da SLA che abbiano subito danni EmCell, Nemmeno la Fondazione ha ricevuto segnalazioni verificabili di miglioramento in seguito al trattamento con EmCell.
Terapia con cellule staminali è perseguito da una serie di istituzioni credibili in tutto il mondo e ALS-TDF sta lavorando con molti dei leader in quell’area. EmCell $15,000 stem cell therapy bears very little resemblance to what is currently being done in leading institutions around the world.
Uno degli elementi principali che rendono l’approccio di EmCell diverso da quello di queste istituzioni leader è il loro metodo di consegna. EmCell inietta cellule staminali fetali nell'addome e nelle vene dei pazienti. Questo approccio è simile alla terapia offerta in Messico, 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.

Cellule staminali d'America (precedentemente chiamato Medra, Inc.)

The chief American commercializer of embryonic stem cell therapy 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. Nel passato, 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 stem cell treatment is not antigenic and has no side effects. Nell'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, Paralisi cerebrale, Sindrome da stanchezza cronica, Depressione, Diabete, Diverticulitis, Epilessia, Impotenza, Immune Suppression, Leucemia, Sclerosi multipla, Parkinsons, Artrite reumatoide, Sickle Cell Anemia, Lesione del midollo spinale, 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, compreso il cancro, 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, Dottorato di ricerca” 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, FARE., 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 stem cell therapy a “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, patologia, 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 stem cell treatment 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. Criobanche internazionali, 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 a più di 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. A marzo 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 stem cell therapy 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.
Riferimenti

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.
Main effects and specific features of embryonic stem cell transplantation. EmCell Web site, accessed accessed June 19, 2006.
The list of conditions and diseases, where we applied embryonic stem cell transplantation with positive results. EmCell Web site, accessed accessed June 19, 2006.
Experience in treatment of oncology patients. EmCell Web site, accessed accessed June 19, 2006.
Cord blood review. ALS Web site, dicembre 2002.
What’s happening with cord blood. ALS-TDF Web site, dicembre 2002.
Wahlberg D. FDA studies ALS doctor, trattamento. Atlanta Journal-Constitution, Marzo 29, 2003.
Hundley K. Mining medical waste. San. Petersburg Times May 12, 2003.
Review of EmCell by ALS-TDF. ALS-TDF Web site, Giugno 2002.
Rader W. Documents faxed in 1997.
Fetal stem cell therapy factsheet. Maggio 2004.
Decision after non-adoption. In the matter iof the accusation against William C. Rader, MD. Medical Board of California Case No. 20-2010-205857, ottobre 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.

 

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