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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Human spongiosa mesenchymal stem cells fail to generate cardiomyocytes in vitro
Svetlana Mastitskaya1, Bernd Denecke
1Interdisciplinary Centre for Clinical Research (IZKF), BIOMAT, RWTH Aachen University, Aachen, Germany. svetlana.mastitskaya@googlemail.com
Insights
Human mesenchymal stem cells (hMSCs) show limited potential for cardiac regeneration. Despite differentiation attempts, hMSCs did not form functional heart cells, questioning their use in treating heart disease.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Human mesenchymal stem cells (hMSCs) are explored for ischemic heart disease therapy.
- Previous in vitro studies on hMSC cardiac differentiation yielded controversial and unreproducible results.
Purpose of the Study:
- To analyze various protocols for cardiac differentiation of hMSCs.
- To investigate the impact of chemical treatments and culture methods on hMSC cardiomyogenic potential.
Main Methods:
- Analysis of published hMSC cardiac differentiation protocols.
- Application of differentiation cocktails, biomaterial scaffolds, and co-culture techniques.
- Treatment with 5'-azacytidine and trichostatin A.
Main Results:
- hMSCs failed to generate functionally active cardiomyocytes in vitro.
- Some cells showed increased cardiac-specific gene expression after treatment and co-culture.
- Differentiation protocols, chemical treatments, and co-culture did not yield functional cardiomyocytes.
Conclusions:
- hMSCs do not appear to form functional cardiomyocytes in vitro.
- The use of hMSCs for mechanical heart muscle repair is questionable based on these findings.
Background:
Human mesenchymal stem cells (hMSCs) are broadly discussed as a promising cell population amongst others for regenerative therapy of ischemic heart disease and its consequences. Although cardiac-specific differentiation of hMSCs was reported in several in vitro studies, these results were sometimes controversial and not reproducible.
Results:
In our study we have analyzed different published protocols of cardiac differentiation of hMSCs and their modifications, including the use of differentiation cocktails, different biomaterial scaffolds, co-culture techniques, and two- and three-dimensional cultures. We also studied whether 5'-azacytidin and trichostatin A treatments in combination with the techniques mentioned above can increase the cardiomyogenic potential of hMSCs. We found that hMSCs failed to generate functionally active cardiomyocytes in vitro, although part of the cells demonstrated increased levels of cardiac-specific gene expression when treated with differentiation factors, chemical substances, or co-cultured with native cardiomyocytes.
Conclusion:
The failure of hMSCs to form cardiomyocytes makes doubtful the possibility of their use for mechanical reparation of the heart muscle.
