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Published on: January 18, 2019
Characteristics and Cardiomyogenic Potential of Rat Fetal Cardiac Progenitor Cells at Different Developmental Stage
Tung Nguyen Thanh1, Him Cha Shin2, Hwal Ran Kim3
11Department of Biomedical Sciences, Inha University College of Medicine, 100 Inharo, Nam-gu, Incheon, 22212 Korea.
Insights
Rat fetal cardiac progenitor cells (rFCPCs) isolated at different embryonic stages (E12 and E15) exhibit distinct properties. These developmental differences impact their characteristics and differentiation potential, crucial for cardiovascular regeneration therapies.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Stem Cell Biology
Background:
- Cardiac progenitor cells (CPCs) are crucial for heart development and repair.
- Identifying distinct CPC populations based on developmental stage is essential for understanding their potential.
- Previous studies have identified various CPCs with differentiation capabilities.
Purpose of the Study:
- To directly compare the characteristics of rat fetal cardiac progenitor cells (rFCPCs) isolated at embryonic day 12 (E12) and embryonic day 15 (E15).
- To evaluate the influence of developmental stage on rFCPC properties, including marker expression, proliferation, and differentiation potential.
- To determine the optimal CPC source for cardiovascular regeneration therapies.
Main Methods:
- Isolation and characterization of rFCPCs from E12 and E15 rat embryos.
- Flow cytometry analysis for mesenchymal stem cell markers (CD105, CD73, CD29, CD34, CD45).
- Quantitative analysis of stem cell markers (Oct4, Nkx2.5) and proliferation rates (doubling time).
- Assessment of cardiomyogenic differentiation potential using immunocytochemistry for cardiac markers (α-MHC, cTnT, cTnC, Cx43).
Main Results:
- Both E12 and E15 rFCPCs expressed mesenchymal stem cell markers but lacked hematopoietic markers.
- E12 rFCPCs showed higher Oct4 and lower Nkx2.5 expression compared to E15 rFCPCs, with significant changes observed by passage 5.
- E12 rFCPCs had a longer average doubling time than E15 rFCPCs.
- Both cell types differentiated into cardiomyocytes, but E15 rFCPCs exhibited more intense α-MHC staining.
Conclusions:
- Developmental stage significantly influences the properties and differentiation potential of fetal cardiac progenitor cells.
- E15 rFCPCs may possess a more robust cardiomyogenic differentiation capacity compared to E12 rFCPCs.
- These findings highlight the importance of considering developmental origins when selecting CPCs for cell-based cardiovascular therapies.
Abstract:
In recent years, several kinds of cardiac progenitor cells have been identified and isolated from heart tissue. These cells showed differentiation potential into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro and in vivo. Morphogenetic events are tightly regulated during development to determine cell destiny and reshape the embryonic lineage. In this study, we directly compared the characteristics of rat fetal cardiac progenitor cells (rFCPCs) isolated from the chamber formation stage at embryonic day 12 (E12) and at the septation stage of E15. Both kinds of rFCPCs expressed mesenchymal stem cell markers (CD105, CD73, and CD29) but not CD34 and CD45. The E12 rFCPCs expressed a high level of Oct4 compared to E15 until passage 5 and showed a steep decline of Nkx2.5 expression at passage 5. However, Nkx2.5 expression at E15 was maintained until passage 5 and Oct4 expression slightly increased at passage 5. We also detected an intense staining for Oct4 antibody in E12 heart tissue sections. The average doubling time of the E12 rFCPCs from passage 3 to passage 15 was about 5 hours longer than E15. These cells could also be induced into cardiomyocytes expressing α-MHC, cTnT, cTnC, and Cx43 under cardiomyogenic culture conditions and rFCPCs at E15 showed more intense staining of α-MHC than cells at E12 by immunocytochemistry. Taken together, our results show that developmental differences between E12 and E15 may influence their properties and differentiation. Furthermore those differences should be considered when deciding on the optimal cell source for cell replacement therapy in cardiovascular regeneration.
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