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题目:: Co-culture with mature islet cells augments the differentiation of insulin-producing cells from pluripotent stem cells.
作者:: Oh(Bea Jun),Oh(Seung-Hoon),Choi(Jin Myung),Jin(Sang-Man),Shim(Woo-Young),Lee(Myung-Shik),Lee(Moon-Kyu),Kim(Kwang-Won),Kim(Jae Hyeon)
状态:: 发布时间2015-02-19 , 更新时间 2015-02-19
期刊:: Stem Cell Rev
摘要:: Islet transplantation has been hampered by the shortage of islet donors available for diabetes therapy. However, pluripotent stem cells (PSCs) can be an alternative source of insulin-producing cells (IPCs) because of their capacity for self-renewal and differentiation. We described a method to efficiently differentiate PSCs into IPCs by co-culturing mature islets with directed-differentiated pancreatic endoderm (PE) cells from mouse and human PSCs. PE cells co-cultured with islet cells or islet cell-derived conditioned medium (CM) showed increased expression levels of β-cell markers; significantly higher levels of proinsulin- and Newport Green (NG)-positive cells, which revealed the characteristics of insulin producing cells; and increased insulin secretion upon glucose stimulation. Co-culturing human PE cells with islet cells was also effective to differentiate PE cells into IPCs. Diabetic nude mice transplanted with co-cultured cells exhibited restored euglycemia, human C-peptide release, and improved glucose tolerance. Immunohistochemistry revealed that insulin+/C-peptide + cells existed in the grafted tissues. These results suggest that mature islet cells can increase the differentiation efficiency of PE cells into mature IPCs via paracrine effects.
语言:: eng
DOI:: 10.1007/s12015-014-9554-8

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