Clinical trials using human pluripotent stem cells worldwide

Human pluripotent stem cells can self-renew indefinitely in culture while maintaining the ability to become any cell type in the human body. Over the last decade, a growing number of clinical trials using these stem cells to develop novel cellular treatments for diseases, such as Parkinson’s Disease, blindness, diabetes and cancer, have been initiated in various parts of the world.

Now, a review paper that systematically categorizes and summarizes all completed and ongoing clinical trials with human pluripotent stem cells has been published in the journal Cell Stem Cell. The review uncovers that more than 1200 patients have now received treatment with pluripotent stem cell products as part of 116 different clinical trials. In total, more than 100 billion cells have been administered to patients across the globe. The trials are targeting 34 different indications, the majority of which are eye diseases, brain diseases and cancer.

Much of the initial underlying information in the review came from the US based website clinicaltrials.gov, which hosts information on clinical trials worldwide. However, clinicaltrials.gov is not an exhaustive database, and trial information is often not updated on the site. Furthermore, the website is based on user information which is not validated by authorities. Therefore, manual curation of trials through information from other national databases, publications, press releases and personal communication with trial representatives was necessary to validate the information going into the review.

We very thoroughly went through every single clinical trial, and we contacted the responsible sponsor of each trial to validate the activity status of the trial and to receive the most recent trial updates. This way, we made sure that the information we included in the paper was correct and up to date, and we excluded trials which we were not able to validate through the sponsor or third-parties.

“Dr Main is a consultant from Australia and Dr Carpenter is a consultant based on the West Coast of the US, while I myself is based in Copenhagen. Collectively, we've therefore been in a good position to cover activities around the world. Our contact with trial sponsors also allowed us to, for the first time, actually count how many patients have been transplanted with human pluripotent stem cell products in total, ever since these products first came into clinical trial, ” said Associate Professor Agnete Kirkeby.

Despite concerns about tumor formation, no cases of this have been reported from the more than 1200 patients receiving pluripotent stem cell treatments as part of controlled clinical trials so far. Overall, the review thereby concludes that there does not appear to be any generalizable safety concerns for these kinds of novel cellular therapies.

The review is the first of its kind to provide compiled information on immunosuppression used in the different pluripotent cell therapy clinical trials. Immunosuppression inhibits the body's immune system and prevents rejection of the transplanted cells and it is therefore an important part of designing and developing safe stem cell trials.

“When contacting the responsible clinical trial sponsors, we found them to be very helpful in providing additional trial information, and we sensed a great deal of excitement around getting this review out as a resource to the field. Many people have asked us for access to the review before it's even published,”  said Associate Professor Kirkeby.

It is anticipated that this review on the landscape of human pluripotent stem cells in clinical use will be an invaluable resource to stem cell scientists all over the world. The authors have plans to update the review on a regular basis, as the field is rapidly progressing with new therapies and new clinical trials each year.

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