I don’t know why, but people still bet on who will inject human embryonic stem cell (ESC) derived cells for the first time ever into a patient – Geron or Advanced Cell Technology (ACT)? Geron’s phase I clinical trial is still on hold and while we are expecting an answer from the FDA , none of the patients were officially treated yet. ACT filed an IND application to the FDA for first human clinical trial using ESC to treat eye disease and hope to start it this year. So, everybody is taking a deep breath before these 2 clinical trials will start officially in US.
Excerpt from Knoepfler Lab Stem Cell Blog:
Still no news from Geron on that clinical hold by the FDA that is now nearly a year long. I’m told (no big surprise) that ACT investors are hoping the Geron hold is very long and that ACT will become the first biotech with an FDA-approved hESC-based clinical trial. I still think Geron will be first but haven’t heard anything in a while.
Meanwhile, countries such as India do not have an FDA and such trials are regulated differently. You may be surprised to know, but more than 4 years ago the first patient ever was injected by ESC-derived cells in the Institute of Transplantation Sciences, India. More than that, results of this experiment were published in a well respected peer-reviewed journal Transplantation Proceedings. We were so excited about this remarkable event that we started to discuss online:
This paper describes a case report of tolerance induction in a male kidney transplant recipient, in which donor bone marrow (from his sister) was “superpotentiated” by the co-administration of embryonic stem cells generated from the sister that were administered with the bone marrow.
The recipient appeared healthy at 100 days post procedure and did not require immune suppression, which is a fundamental advancement in the field of transplant immunology.
I’d like to bring up a methodological part, described in the paper:
We planned to subject her to long ovarian stimulation simultaneous with our regular tolerance induction protocol. The retrieved oocyte would be denuded and enucleated using an aspiration technique. We planned to use a single cumulus cell from the same donor to inject into the enucleated oocyte (somatic cell nuclear transfer [SCNT]-oocyte). The SCNT-oocyte would be developed into a blastocyst. The inner cell mass hatched from this blastocyst would be cocultured with her own unmodified BM for directed differentiation into HSCs. We planned to analyse these cells for their counts, viability, CD34+/45+ counts, as well as to detect molecular markers for pluripotency and karyotyping. We planned to infuse them into the periphery of recipient after confirming their counts and viability. Renal transplantation was to be performed 1 week after the cell infusion…
The Institutional Review Board approved the study protocol and informed consent forms.
Dr. Trivedi, who was brave enough to perform this procedure for the first time in clinic, appeared to be a very nice guy and kindly replied to our request about follow-up of this patient and their future plans:
In response to our coverage of this event, the senior author of the paper, Dr. H.L. Trivedi has requested us to post the following:
” Thank you for your interest in our work. I would like to draw the attention of your readership that this patient will be finishing 1 year without any rejection/ teratoma. He is doing well. We have also implemented the same protocol in 35 more patients successfully. H.L. Trivedi “
Now, 4 years after, I was curious enough to ask Dr. Triverdi about follow-up of this trial via email. Especially I was curious about safety of procedure and I got the following answer:
“We have now abandoned hESC since they were not so potent as thought to be. In fact now we use human adipose tissue derived mesenchymal stem cells which we have patented and these show wonderful results. We have been able to treat renal Tx patients with these cells and our patients do well with minimum/ no immunosuppression.
None of the patients has developed any tumor masses etc, because we differentiated cells into hematopoietic cell lines before transplanting them in to recipients. Many thanks for interest in our work. H.L. Trivedi”
Well, still a lot of questions remain, because they didn’t publish follow-up results (even if it was not clinically beneficial) after this clinical case. But I think this first paper in Transplantation Proceedings is very important, because its claim is a first (is that what you meant?). I was really thrilled by the fact that the first clinical use of ESC-derived cells was done with tolerance induction in organ transplant purpose and that it was with hematopoietic derivatives. The most important message is that, despite the fact that undifferentiated ESC (hematopoietic cells were not purified from cultured ESC) were injected, the therapy appeared to be safe long-term. For some reasons I feel happy for my Indian colleagues, maybe because I spent some years of my life in transplantation medicine.