Transient secretion of VEGF protein from transplanted hiPSC-CMs enhances engraftment and improves rat heart function post MI

Cell-based therapies offer an exciting and novel treatment for heart repair following myocardial infarction (MI). However, these therapies often suffer from poor cell viability and engraftment rates, which involve many factors, including the hypoxic conditions of the infarct environment. Meanwhile,...

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Veröffentlicht in:Molecular therapy 2023-01, Vol.31 (1), p.211-229
Hauptverfasser: Ai, Xuefeng, Yan, Bingqian, Witman, Nevin, Gong, Yiqi, Yang, Li, Tan, Yao, Chen, Ying, Liu, Minglu, Lu, Tingting, Luo, Runjiao, Wang, Huijing, Chien, Kenneth R., Wang, Wei, Fu, Wei
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Sprache:eng
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Zusammenfassung:Cell-based therapies offer an exciting and novel treatment for heart repair following myocardial infarction (MI). However, these therapies often suffer from poor cell viability and engraftment rates, which involve many factors, including the hypoxic conditions of the infarct environment. Meanwhile, vascular endothelial growth factor (VEGF) has previously been employed as a therapeutic agent to limit myocardial damage and simultaneously induce neovascularization. This study took an approach to transiently overexpress VEGF protein, in a controlled manner, by transfecting human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with VEGF mRNA prior to transplantation. The conditioning of iPSC-CMs with VEGF mRNA ultimately led to greater survival rates of the transplanted cells, which promoted a stable vascular network in the grafted region. Furthermore, bulk RNA transcriptomics data and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) and AGE-RAGE signaling pathways were significantly upregulated in the VEGF-treated iPSC-CMs group. The over-expression of VEGF from iPSC-CMs stimulated cell proliferation and partially attenuated the hypoxic environment in the infarcted area, resulting in reduced ventricular remodeling. This study provides a valuable solution for the survival of transplanted cells in tissue-engineered heart regeneration and may further promote the application of modified mRNA (modRNA) in the field of tissue engineering. [Display omitted] Fu et al. describe a study combining novel mRNA technology with cell-based therapy to enhance cardiac regeneration. This study provides a reliable solution for increasing the survival rates of transplanted cells in cardiac muscle and may further promote the application of modified mRNA in the field of tissue engineering.
ISSN:1525-0016
1525-0024
DOI:10.1016/j.ymthe.2022.08.012