AUTHOR=Pellegrini Silvia , Zamarian Valentina , Sordi Valeria 

TITLE=Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes

JOURNAL=Transplant International

VOLUME=Volume 35 - 2022

YEAR=2022

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2022.10575

DOI=10.3389/ti.2022.10575

ISSN=1432-2277

ABSTRACT=Allogeneic islet transplantation allows the reestablishment of glycaemic control with the possibility of insulin independence, but it is severely limited by the scarcity of organ donor. A new source of insulin-producing cells would significantly increase the possibility that cell therapy becomes a broad and standard therapy for diabetes treatment. 
Recent breakthroughs in stem cell biology, especially the establishment of the pluripotent stem cells (PSC) techniques, have generated great enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Beta cell replacement therapy with stem cells is drawing nearer the clinical application thanks to the increase in knowledge of the stages that regulate the development of the β cell, leading to the setup of more efficient protocols for the differentiation of PSC into β cells. Nowadays, PSC-derived β cells are appearing in the first pioneering clinical trials. 
The safety issue related to the final cellular product prior implantation assumes therefore crucial importance. In fact, PSC can be differentiated into functional β cells in vitro, but not all the cells might reach complete differentiation and potentially a fraction of cells might remain undifferentiated and expose to a risk of teratoma formation upon transplantation. Although recent protocol refinements have reduced this risk, the foreseeable implementation of stem cell-based therapies in thousands of patients calls for caution. One single case of stem cell derived tumour may set the field back for years.
In this review, we focus on the potential approaches to increase the safety of PSC-derived β cells. These can be summarized in four different strategies: the safest reprogramming of somatic cells into iPSC, the selection of pure differentiated pancreatic cells, the depletion of contaminant PSC in the final cell product, and the control of tumorigenic cells with suicide genes.