Abstract
Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the most widely practiced treatment. However, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to a high blood glucose level. However, the determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for the treatment of diabetes is still debated. While hPSC-derived beta cells are perceived as the ultimate candidate, their efficiency needs further improvement in order to obtain a sufficient number of glucose responsive beta cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address the co-generation of functionally relevant islet cell subpopulations and structural properties contributing to the glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.
Highlights
Diabetes mellitus occurs due to the loss or impaired function of insulin-secreting pancreatic beta cells
For diabetes human pluripotent stem cells (hPSCs) derived from the inner cell mass (ICM)pluripotent of the blastocyst hiPSCs for diabetes treatment. hPSCs derived from the inner cell mass (ICM) of the blastocyst and hiPSCs generated from patient somatic cells can be differentiated into pancreatic progenitors that mature generated from patient somatic cells can be differentiated into pancreatic progenitors that mature in in vivo into glucose-responsive beta cells following transplantation
Substantial progress has been achieved in the differentiation of hPSCs into pancreatic beta cells
Summary
Diabetes mellitus occurs due to the loss or impaired function of insulin-secreting pancreatic beta cells. Have been designed, the in vitro generation of functional pancreatic beta cells has differentiation been challenging hPSC-derived pancreatic progenitor cells that give rise to mono-hormonal insulin-secreting cells (Figures 1 and 2). Only one clinical trial has been approved for hPSC-derived product for T1D within the body have been designed, the in vitro generation of functional pancreatic beta cells has treatment, led by the company ViaCyte (ClinicalTrials.gov Identifier: NCT03163511, NCT02239354). HPSCs derived from the inner cell mass (ICM) of the blastocyst and hiPSCs generated from patient somatic cells can be differentiated into pancreatic progenitors that mature generated from patient somatic cells can be differentiated into pancreatic progenitors that mature in in vivo into glucose-responsive beta cells following transplantation. Generated in vitro can be directly transplanted into mouse model
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