“…Similarly, Nair et al (2019) and Veres et al (2019) have used insulin and CD49a, respectively, as b cell maturation markers to perform magnetic sorting and increase the purity of their cell product. Recently, Parent et al (2022) described a scalable magnetic sorting method using monoclonal antibodies against SC-islet progenitors that results in generation of SC-islets with improved glucose-stimulated insulin secretion and reduced growth upon transplantation.…”
Section: Current Strategies For Removal Of Off-target Cellsmentioning
“…Similarly, Nair et al (2019) and Veres et al (2019) have used insulin and CD49a, respectively, as b cell maturation markers to perform magnetic sorting and increase the purity of their cell product. Recently, Parent et al (2022) described a scalable magnetic sorting method using monoclonal antibodies against SC-islet progenitors that results in generation of SC-islets with improved glucose-stimulated insulin secretion and reduced growth upon transplantation.…”
Section: Current Strategies For Removal Of Off-target Cellsmentioning
“…CD9 was found as a negative cell-surface marker for β cells (Li et al, 2020 ). Furthermore, a recent study identified three monoclonal antibodies to mark islet endocrine cell populations, which were used for magnetic sorting to enrich insulin-expressing cells with a high fraction of recovery (Parent et al, 2022 ). Fig.…”
Section: Concerns and Recent Advances In Stepwise Pancreatic β Cell D...mentioning
Pancreatic β cells differentiated from stem cells provide promise for cell replacement therapy of diabetes. Human pluripotent stem cells could be differentiated into definitive endoderm, followed by pancreatic progenitors, and then subjected to endocrinal differentiation and maturation in a stepwise fashion. Many achievements have been made in making pancreatic β cells from human pluripotent stem cells in last two decades, and a couple of phase I/II clinical trials have just been initiated. Here, we overview the major progresses in differentiating pancreatic β cells from human pluripotent stem cells with the focus on recent technical advances in each differentiation stage, and briefly discuss the current limitations as well.
“…It has been found that as few as two ESC colonies implanted into immunodeficient mice can result in teratoma formation; when the clumps were trypsinized to single-cell suspensions before injection, 245 cells were sufficient to form teratomas after 10 weeks (8). Several groups have reported the formation of teratomatous tissue elements in grafts when not purified PSC-derived pancreatic endoderm cells were infused in mice (9)(10)(11)(12)(13).…”
Allogeneic islet transplantation allows for the re-establishment of glycemic control with the possibility of insulin independence, but is severely limited by the scarcity of organ donors. However, a new source of insulin-producing cells could enable the widespread use of cell therapy for diabetes treatment. Recent breakthroughs in stem cell biology, particularly pluripotent stem cell (PSC) techniques, have highlighted the therapeutic potential of stem cells in regenerative medicine. An understanding of the stages that regulate β cell development has led to the establishment of protocols for PSC differentiation into β cells, and PSC-derived β cells are appearing in the first pioneering clinical trials. However, the safety of the final product prior to implantation remains crucial. Although PSC differentiate into functional β cells in vitro, not all cells complete differentiation, and a fraction remain undifferentiated and at risk of teratoma formation upon transplantation. A single case of stem cell-derived tumors may set the field back years. Thus, this review discusses four approaches to increase the safety of PSC-derived β cells: reprogramming of somatic cells into induced PSC, selection of pure differentiated pancreatic cells, depletion of contaminant PSC in the final cell product, and control or destruction of tumorigenic cells with engineered suicide genes.
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