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

被引:7
作者
Ghezelayagh, Zahra [1 ,2 ]
Zabihi, Mahsa [2 ,3 ]
Zarkesh, Ibrahim [4 ]
Goncalves, Carla A. C. [5 ]
Larsen, Michael [5 ]
Hagh-parast, Newsha [2 ]
Pakzad, Mohammad [2 ]
Vosough, Massoud [6 ]
Arjmand, Babak [7 ]
Baharvand, Hossein [1 ,2 ]
Larijani, Bagher [8 ]
Grapin-Botton, Anne [5 ,9 ]
Aghayan, Hamid Reza [7 ]
Tahamtani, Yaser [2 ,10 ]
机构
[1] Univ Sci & Culture, ACECR, Dept Dev Biol, Fac Basic Sci & Adv Technol Biol, Tehran, Iran
[2] Univ Sci & Culture, ACECR, Dept Stem Cells & Dev Biol, Fac Basic Sci & Adv Technol Biol, Tehran, Iran
[3] Univ Sci & Culture, ACECR, Dept Genet, Fac Basic Sci & Adv Technol Biol, Tehran, Iran
[4] ACECR, Dept Cell Engn, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran, Iran
[5] Univ Copenhagen, Novo Nordisk Fdn Ctr Stem Cell Biol DanStem, Fac Hlth Sci, Copenhagen, Denmark
[6] ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Regenerat Med, Tehran, Iran
[7] Univ Tehran Med Sci, Endocrinol & Metab Mol Cellular Sci Inst, Cell Therapy & Regenerat Med Res Ctr, Tehran, Iran
[8] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran
[9] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany
[10] ACECR, Royan Inst Reprod Biomed, Reprod Epidemiol Res Ctr, Tehran, Iran
关键词
AggreWell; Co-culture; Fetal mesenchyme; Niche-specific; Pancreas; Spheroid; EMBRYONIC STEM-CELLS; INSULIN-PRODUCING CELLS; BETA-CELLS; EFFICIENT GENERATION; CULTURE; MATURATION; EXPANSION; TISSUES; ISLET; LINES;
D O I
10.1007/s12015-021-10266-z
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:360 / 377
页数:18
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