Improved Differentiation of hESC-Derived Pancreatic Progenitors by Using Human 
Fetal Pancreatic Mesenchymal Cells in a Micro-scalable Three-Dimensional 
Co-culture System.

Ghezelayagh, Zahra; Zabihi, Mahsa; Zarkesh, Ibrahim; Gonçalves, Carla A C; Larsen, Michael; Hagh-Parast, Newsha; Pakzad, Mohammad; Vosough, Massoud; Arjmand, Babak; Baharvand, Hossein; Larijani, Banafshé; Grapin-Botton, Anne; Aghayan, Hamid Reza; Tahamtani, Yaser

doi:10.1007/s12015-021-10266-z

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Improved Differentiation of hESC-Derived Pancreatic Progenitors by Using Human Fetal Pancreatic Mesenchymal Cells in a Micro-scalable Three-Dimensional Co-culture System.

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Grapin-Botton, Anne
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Ghezelayagh, Z., Zabihi, M., Zarkesh, I., Gonçalves, C. A. C., Larsen, M., Hagh-Parast, N., et al. (2022). Improved Differentiation of hESC-Derived Pancreatic Progenitors by Using Human Fetal Pancreatic Mesenchymal Cells in a Micro-scalable Three-Dimensional Co-culture System. Stem cell reviews and reports, 18(1), 360-377. doi:10.1007/s12015-021-10266-z.

Cite as: https://hdl.handle.net/21.11116/0000-000B-0355-2

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.