title: Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice.
abstract: Pluripotent human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating patients with diabetes. To investigate the impact of the host recipient on hESC-derived pancreatic progenitor cell maturation, cells were transplanted into immunodeficient SCID-beige mice or nude rats. Following the transplant, basal human C-peptide levels were consistently higher in mice compared with rats, but only rats showed robust meal- and glucose-responsive human C-peptide secretion by 19-21 weeks. Grafts from rats contained a higher proportion of insulin:glucagon immunoreactivity, fewer exocrine cells, and improved expression of mature β cell markers compared with mice. Moreover, ECM-related genes were enriched, the collagen network was denser, and blood vessels were more intricately integrated into the engrafted endocrine tissue in rats relative to mice. Overall, hESC-derived pancreatic progenitor cells matured faster in nude rats compared with SCID-beige mice, indicating that the host recipient can greatly influence the fate of immature pancreatic progenitor cells post-transplantation.
authors.affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Bruin
authors.affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Asadi
authors.affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Fox
authors.affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Suheda
authors.initials: S
authors.lastname: Erener
authors.affiliation: BetaLogics Venture, Janssen R&D LLC, 1000 Route 202 South, Room J108A, Raritan, NJ 08869, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Rezania
authors.affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Surgery, University of British Columbia, 950 West 10(th) Avenue, Vancouver, BC V5Z 1M9, Canada. Electronic address: tim.kieffer@ubc.ca.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000032:analysis; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D010179:Pancreas / Q000166:cytology*; D051381:Rats; D011923:Rats, Nude; D013045:Species Specificity; D033581:Stem Cell Transplantation
chemical_list: D002096:C-Peptide