Pluripotent Stem Cells in Clinical Setting—New Developments and Overview of Current Status

Abstract

The number of clinical trials using human pluripotent stem cells (hPSC) - both embryonic and induced pluripotent stem cells (hESC/iPSC) - has expanded in the last several years beyond expectations. By the end of 2021, a total of 90 trials had been registered in 13 countries with over 3000 participants. However, only USA, Japan, China, and the UK are conducting both hESC- and hiPSC-based trials. Together USA, Japan, and China have registered 78% (70 out of 90) of all trials worldwide. More than a half of all trials (51%) are focused on treatment of degenerative eye diseases and malignancies, enrolling nearly 2/3 of all participants in hPSC-based trials. Although no serious adverse event resulting in death or morbidity due to hPSC-based cellular therapy received have been reported, information about safety and clinical efficacy are still very limited. With the availability of novel technologies for precise genome editing, a new trend in the development of hPSC-based cellular therapies seems to be emerging. Engineering universal donor hPSC lines has become a holy grail in the field. Indeed, because of its effectiveness and simplicity nanomedicine and in vivo delivery of gene therapy could become more advantageous than cellular therapies for treatment of multiple diseases. In future, for the best outcome, hPSC-based cellular therapy might be combined with other technological advancements such as biomimetic epidural electrical stimulation that can restore trunk and leg motor functions after complete spinal injury.

Matrix-free human pluripotent stem cell manufacturing by seed train approach and intermediate cryopreservation

“…Recently, an increasing number of clinical trials based on hPSC-derived progenies has been initiated [2]. However, depending on the target therapy, estimated cell doses per patient range from 10 9 to 10 10 cells [3,4].…”

Hypoimmunogenic Human Pluripotent Stem Cells as a Powerful Tool for Liver Regenerative Medicine

“…From iPSC discovery by Takahashi and Yamanaka in 2006 [1], various strategies have been developed and new ones continue to emerge aiming at optimizing the technology and improving safety and clinical use. Clinical trials using iPSCs are rapidly increasing and they are mainly focused on ocular diseases, malignancies, neural degenerative disorders and cardiovascular diseases [2]. However, the cost of autologous iPSC therapy, due to reprogramming, differentiation, and quality control of patient-specific iPSCs, is not sustainable and forced the research towards the use of allogeneic cells with several efforts trying to solve the immune rejection issue caused by HLA mismatch.…”

The Manufacture of Xeno- and Feeder-Free Clinical-Grade Human Embryonic Stem Cell Lines: First Step for Cell Therapy

“…Cell therapies involving hESC have shown very promising results for the treatment of certain diseases, especially age-related macular degeneration, and confirmed safety of hESC-derived cells for humans [ 7 , 8 , 9 , 10 ]. These results stand behind the rise of cell therapies using hESCs, as their number increased from 11 trials in 2015, followed by 32 trials in 2019 to 47 trials in 2021 [ 11 , 12 , 13 , 14 ]. However, the prospective clinical use of hESC-derived cells needs to be further examined from the point of their safety, quality, functionality, and efficacy.…”