Co-culture with Mature Islet Cells Augments the Differentiation of Insulin-Producing Cells from Pluripotent Stem Cells
- Authors
- 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
- Issue Date
- Feb-2015
- Publisher
- HUMANA PRESS INC
- Keywords
- Pluripotent stem cells; Insulin-producing cells; Co-culture; beta-cell differentiation; Diabetes; Transplantation
- Citation
- STEM CELL REVIEWS AND REPORTS, v.11, no.1, pp.62 - 74
- Journal Title
- STEM CELL REVIEWS AND REPORTS
- Volume
- 11
- Number
- 1
- Start Page
- 62
- End Page
- 74
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10832
- DOI
- 10.1007/s12015-014-9554-8
- ISSN
- 1550-8943
- Abstract
- 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 beta-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.
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