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Pancreatic Endoderm‐Derived From Diabetic Patient‐Specific Induced Pluripotent Stem Cell Generates Glucose‐Responsive Insulin‐Secreting Cells
Author(s) -
Rajaei Bahareh,
Shamsara Mehdi,
Amirabad Leila Mohammadi,
Massumi Mohammad,
Sanati Mohammad Hossein
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25459
Subject(s) - induced pluripotent stem cell , biology , stem cell , pdx1 , microbiology and biotechnology , endoderm , cellular differentiation , enteroendocrine cell , induced stem cells , cell therapy , insulin , endocrinology , medicine , cancer research , embryonic stem cell , endocrine system , biochemistry , islet , hormone , gene
Human‐induced pluripotent stem cells (hiPSCs) can potentially serve as an invaluable source for cell replacement therapy and allow the creation of patient‐ and disease‐specific stem cells without the controversial use of embryos and avoids any immunological incompatibility. The generation of insulin‐producing pancreatic β‐cells from pluripotent stem cells in vitro provides an unprecedented cell source for personal drug discovery and cell transplantation therapy in diabetes. A new five‐step protocol was introduced in this study, effectively induced hiPSCs to differentiate into glucose‐responsive insulin‐producing cells. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, primitive gut‐tube endoderm, posterior foregut, pancreatic endoderm, and endocrine precursor. Each stage of differentiation were characterized by stage‐specific markers. The produced cells exhibited many properties of functional β‐cells, including expression of critical β‐cells transcription factors, the potency to secrete C‐peptide in response to high levels of glucose and the presence of mature endocrine secretory granules. This high efficient differentiation protocol, established in this study, yielded 79.18% insulin‐secreting cells which were responsive to glucose five times higher than the basal level. These hiPSCs‐derived glucose‐responsive insulin‐secreting cells might provide a promising approach for the treatment of type I diabetes mellitus. J. Cell. Physiol. 232: 2616–2625, 2017. © 2016 Wiley Periodicals, Inc.