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Review
. 2021 Apr 20;2(4):100238.
doi: 10.1016/j.xcrm.2021.100238.

Applications of iPSC-derived beta cells from patients with diabetes

Kristina G Maxwell  1   2 , Jeffrey R Millman  1   2
Affiliations
Review

Applications of iPSC-derived beta cells from patients with diabetes

Kristina G Maxwell et al. Cell Rep Med. .

Abstract

Improved stem cell-derived pancreatic islet (SC-islet) differentiation protocols robustly generate insulin-secreting β cells from patient induced pluripotent stem cells (iPSCs). These advances are enabling in vitro disease modeling studies and the development of an autologous diabetes cell replacement therapy. SC-islet technology elucidates key features of human pancreas development and diabetes disease progression through the generation of pancreatic progenitors, endocrine progenitors, and β cells derived from diabetic and nondiabetic iPSCs. Combining disease modeling with gene editing and next-generation sequencing reveals the impact of diabetes-causing mutations and diabetic phenotypes on multiple islet cell types. In addition, the supply of SC-islets, containing β and other islet cell types, is unlimited, presenting an opportunity for personalized medicine and overcoming several disadvantages posed by donor islets. This review highlights relevant studies involving iPSC-β cells and progenitors, encompassing new conclusions involving cells from patients with diabetes and the therapeutic potential of iPSC-β cells.

Keywords: CRISPR; beta cells; cell therapy; diabetes; differentiation; disease modeling; iPS cells; islets; pluripotency; stem cells.

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Conflict of interest statement

K.G.M. and J.R.M. are inventors on licensed patents and patent applications related to the SC-β cell technology described in this manuscript. J.R.M. is a consultant for Sana Biotechnology. K.G.M. is the chief operations officer and co-founder of Salentra Biosciences. J.R.M. is the chief scientific officer and co-founder of Salentra Biosciences.

Figures

None
Graphical abstract
Figure 1
Figure 1
Applications of SC-islets from patients with diabetes Patient tissue biopsies can be reprogrammed into induced pluripotent stem cells (iPSCs) and differentiated into stem cell-derived islets (SC-islets) that contain β (SC-β) cells. These SC-islets have applications in disease modeling, gene editing, and cell therapy in animal models. They also provide a source for autologous cell replacement therapy for patients with diabetes. DE, definitive endoderm; EP, endocrine progenitor; PGT, primitive gut tube; PP, pancreatic progenitor.
See this image and copyright information in PMC

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