title: Endothelial cells mediate islet-specific maturation of human embryonic stem cell-derived pancreatic progenitor cells.
abstract: It is well recognized that in vitro differentiation of embryonic stem cells (ESC) can be best achieved by closely recapitulating the in vivo developmental niche. Thus, implementation of directed differentiation strategies has yielded encouraging results in the area of pancreatic islet differentiation. These strategies have concentrated on direct addition of chemical signals, however, other aspect of the developmental niche are yet to be explored. During development, pancreatic progenitor (PP) cells grow as an epithelial sheet, which aggregates with endothelial cells (ECs) during the final stages of maturation. Several findings suggest that the interactions with EC play a role in pancreatic development. In this study, we recapitulated this phenomenon in an in vitro environment by maturing the human ESC (hESC)-derived PP cells in close contact with ECs. We find that co-culture with different ECs (but not fibroblast) alone results in pancreatic islet-specific differentiation of hESC-derived PP cells even in the absence of additional chemical induction. The differentiated cells responded to exogenous glucose levels by enhanced C-peptide synthesis. The co-culture system aligned well with endocrine development as determined by comprehensive analysis of involved signaling pathways. By recapitulating cell-cell interaction aspects of the developmental niche we achieved a differentiation model that aligns closely with islet organogenesis.
authors.affiliation: 1 Department of Bioengineering, University of Pittsburgh, Pittsburgh , Pennsylvania.
authors.forename: Maria
authors.initials: M
authors.lastname: Jaramillo
authors.forename: Shibin
authors.initials: S
authors.lastname: Mathew
authors.forename: Hikaru
authors.initials: H
authors.lastname: Mamiya
authors.forename: Saik Kia
authors.initials: SK
authors.lastname: Goh
authors.forename: Ipsita
authors.initials: I
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D051379:Mice; D041681:NIH 3T3 Cells; D009928:Organ Specificity; D051381:Rats; D015398:Signal Transduction
chemical_list: D007328:Insulin