Abstract
Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cellbased cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BMMSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts.
Original language | English |
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Article number | 1449 |
Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | International Journal of Molecular Sciences |
Volume | 22 |
Issue number | 3 |
DOIs | |
State | Published - 2 Feb 2021 |
Bibliographical note
Funding Information:Funding: This paper was supported by the Hong Kong Research Grants Council (21100818 to K.B.). This paper was also supported by the NRF funded by the Ministry of Education (2017M3A9B3061954 to H.J Park and 2019R1A6A3A13096787 to B.W Park).
Publisher Copyright:
© 2021 by the author. Licensee MDPI, Basel, Switzerland.
Keywords
- Engineered mesenchymal stem cells
- Hepatocyte growth factor
- Human mesenchymal stem cells
- Myocardial infarction
- Vascular regeneration