Journal
REPRODUCTIVE SCIENCES
Volume 26, Issue 5, Pages 669-682Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1933719118786461
Keywords
transdifferentiation; cardiomyocyte-like cells; pancreatic beta cell-like cells; endometrial stromal mesenchymal stem cells; insulin
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Funding
- Bio-industry Technology Development Program [IPET312060-5]
- Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea
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Porcine mesenchymal stem cells (MSCs) are similar to human MSCs, hence considered a valuable model for assessing potential for cell therapy. Porcine adipose-derived MSCs (AD-MSCs) and endometrial stromal MSCs (EMSCs) displayed fibroblast-like morphology and were positive for MSC markers CD73, CD90, and CD105 and negative for hematopoietic markers CD34 and CD45. The EMSCs had similar or slightly higher growth rate compared to AD-MSCs, and similar percentage of cells of both EMSCs and AD-MSCs were at G0/G1 and G2/M phases; however, EMSCs had significantly (P < .05) higher percentage of cells at S phase of cell cycle than AD-MSCs. Transdifferentiation ability to cardiomyocyte-like cells was confirmed in differentiated cells by the expression of lineage-specific marker genes such as DES, ACTA2, cTnT, and ACTC1 by real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, cardiomyocyte-specific protein markers cTnT and ACTC1 were expressed in completely differentiated cells. Endodermal differentiation capacity of EMSCs to pancreatic beta cell-like cells was evident with the changes in morphology and the expression of beta-cell-specific marker genes such as PDX1, GLUT2, SST, NKX6.1, PAX4, and NGN3 as analyzed by RT-qPCR. The differentiated cells secreted insulin and C-peptide upon glucose challenge and also they expressed insulin, PDX1, PAX4, NGN3, and GLUT2 at protein level as assessed by immunostaining confirming the successful differentiation to beta cell-like cells. Porcine EMSCs possess all the characteristics of MSCs and are suitable model for studying molecular mechanisms of cellular differentiation.
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