Improved Differentiation of Hesc-Derived Pancreatic Progenitors by Using Human Fetal Pancreatic Mesenchymal Cells in a Micro‐Scalable Three-Dimensional Co-Culture System Publisher Pubmed



Ghezelayagh Z^{1, 2} ; Zabihi M^{2, 3} ; Zarkesh I⁴ ; Goncalves CAC⁵ ; Larsen M⁵ ; Haghparast N² ; Pakzad M² ; Vosough M⁶ ; Arjmand B⁷ ; Baharvand H^{1, 2} ; Larijani B⁸ ; Grapinbotton A^{5, 9} ; Aghayan HR⁷ ; Tahamtani Y^{2, 10}
Source: Stem Cell Reviews and Reports Published:2022

Abstract

Mesenchymal cells of diverse origins differ in gene and protein expression besides producing varying effects on their organ-matched epithelial cells’ maintenance and differentiation capacity. Co-culture with rodent’s tissue-specific pancreatic mesenchyme accelerates proliferation, self-renewal, and differentiation of pancreatic epithelial progenitors. Therefore, in our study, the impact of three-dimensional (3D) co-culture of human fetal pancreatic-derived mesenchymal cells (hFP-MCs) with human embryonic stem cell-derived pancreatic progenitors (hESC-PPs) development towards endocrine and beta cells was assessed. Besides, the ability to maintain scalable cultures combining hFP-MCs and hESC-PPs was investigated. hFP-MCs expressed many markers in common with bone marrow-derived mesenchymal stem cells (BM-MSCs). However, they showed higher expression of DESMIN compared to BM-MSCs. After co-culture of hESC-PPs with hFP-MCs, the pancreatic progenitor (PP) spheroids generated in Matrigel had higher expression of NGN3 and INSULIN than BM-MSCs co-culture group, which shows an inductive impact of pancreatic mesenchyme on hESC-PPs beta-cells maturation. Pancreatic aggregates generated by forced aggregation through scalable AggreWell system showed similar features compared to the spheroids. These aggregates, a combination of hFP-MCs and hESC-PPs, can be applied as an appropriate tool for assessing endocrine-niche interactions and developmental processes by mimicking the pancreatic tissue. Graphic Abstract: [Figure not available: see fulltext.] © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.