title: Co-culture with mature islet cells augments the differentiation of insulin-producing cells from pluripotent stem cells.
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 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
authors.forename: Bea Jun
authors.initials: BJ
authors.lastname: Oh
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Oh
authors.forename: Jin Myung
authors.initials: JM
authors.lastname: Choi
authors.forename: Sang-Man
authors.initials: SM
authors.lastname: Jin
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Shim
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Moon-Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism / Q000628:therapy; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D058228:Islet Amyloid Polypeptide / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D008819:Mice, Nude; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011384:Proinsulin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D011384:Proinsulin