RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells
by
Paula Mueller 1,2, Markus Wolfien 3
, Katharina Ekat 4, Cajetan Immanuel Lang 5, Dirk Koczan 6, Olaf Wolkenhauer 3,7, Olga Hahn 4, Kirsten Peters 4, Hermann Lang 8, Robert David 1,2,* and Heiko Lemcke 1,2
Paula Mueller 1,2, Markus Wolfien 3, Katharina Ekat 4, Cajetan Immanuel Lang 5, Dirk Koczan 6, Olaf Wolkenhauer 3,7, Olga Hahn 4, Kirsten Peters 4, Hermann Lang 8, Robert David 1,2,* and Heiko Lemcke 1,2
1
Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Rostock University Medical Center, 18057 Rostock, Germany
2
Faculty of Interdisciplinary Research, Department Life, Light & Matter, University Rostock, 18059 Rostock, Germany
3
Institute of Computer Science, Department of Systems Biology and Bioinformatics, University of Rostock, 18057 Rostock, Germany
4
Department of Cell Biology, Rostock University Medical Center, 18057 Rostock, Germany
5
Department of Cardiology, Rostock University Medical Center, 18057 Rostock, Germany
6
Institute of Immunology, Rostock University Medical Center, 18057 Rostock, Germany
7
Stellenbosch Institute of Advanced Study, Wallenberg Research Centre, Stellenbosch University, 7602 Stellenbosch, South Africa
8
Department of Operative Dentistry and Periodontology, Rostock University Medical Center, 18057 Rostock, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 504; https://doi.org/10.3390/cells9020504
Received: 6 December 2019 / Revised: 13 February 2020 / Accepted: 17 February 2020 / Published: 22 February 2020
(This article belongs to the Special Issue Stem Cell Research on Cardiology)
Multipotent adult mesenchymal stromal cells (MSCs) could represent an elegant source for the generation of patient-specific cardiomyocytes needed for regenerative medicine, cardiovascular research, and pharmacological studies. However, the differentiation of adult MSC into a cardiac lineage is challenging compared to embryonic stem cells or induced pluripotent stem cells. Here we used non-integrative methods, including microRNA and mRNA, for cardiac reprogramming of adult MSC derived from bone marrow, dental follicle, and adipose tissue. We found that MSC derived from adipose tissue can partly be reprogrammed into the cardiac lineage by transient overexpression of GATA4, TBX5, MEF2C, and MESP1, while cells isolated from bone marrow, and dental follicle exhibit only weak reprogramming efficiency. qRT-PCR and transcriptomic analysis revealed activation of a cardiac-specific gene program and up-regulation of genes known to promote cardiac development. Although we did not observe the formation of fully mature cardiomyocytes, our data suggests that adult MSC have the capability to acquire a cardiac-like phenotype when treated with mRNA coding for transcription factors that regulate heart development. Yet, further optimization of the reprogramming process is mandatory to increase the reprogramming efficiency.
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Keywords:
mesenchymal stromal cells (MSC); mRNA; miRNA; cardiac reprogramming; cardiac differentiation
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MDPI and ACS Style
Mueller, P.; Wolfien, M.; Ekat, K.; Lang, C.I.; Koczan, D.; Wolkenhauer, O.; Hahn, O.; Peters, K.; Lang, H.; David, R.; Lemcke, H. RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells. Cells 2020, 9, 504.
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