Remote Transplantation of Mesenchymal Stem Cells Protects the Heart Against Ischemia-Reperfusion Injury

Abstract

Cardioprotection can be evoked through extracardiac approaches. This prompted us to investigate whether remote transplantation of stem cells confers protection of the heart against ischemic injury. The cardioprotective effect of subcutaneous transplantation of na€ ıve versus heme oxygenase-1 (HMOX-1)-overexpressing mouse mesenchymal stem cells (MSC) to mice was investigated in hearts subjected to ischemia-reperfusion in a Langendorff perfusion system. Mice were transplanted into the interscapular region with na€ ıve or HMOX-1 transfected MSC isolated from transgenic luciferase reporter mice and compared to sham-treated animals. The fate of transplanted cells was followed by in vivo bioluminescence imaging, revealing that MSC proliferated, but did not migrate detectably from the injection site. Ex vivo analysis of the hearts showed that remote transplantation of mouse adipose-derived MSC (mASC) resulted in smaller infarcts and improved cardiac function after ischemia-reperfusion compared to sham-treated mice. Although HMOX-1 overexpression conferred cytoprotective effects on mASC against oxidative stress in vitro, no additive beneficial effect of HMOX-1 transfection was noted on the ischemic heart. Subcutaneous transplantation of MSC also improved left ventricular function when transplanted in vivo after myocardial infarction. Plasma analysis and gene expression profile of na€ ıve-and HMOX-1-mASC after transplantation pointed toward pentraxin 3 as a possible factor involved in the remote cardioprotective effect of mASC. These results have significant implications for understanding the behavior of stem cells after transplantation and development of safe and noninvasive cellular therapies with clinical applications. Remote transplantation of MSC can be considered as an alternative procedure to induce cardioprotection. STEM CELLS

Mesenchymal stromal cells improve cardiac function and left ventricular remodeling in a heart transplantation model

“…MSC-MVs have also been reported to induce prosurvival genes and down-regulate pro-apoptotic genes, 27 which may provide a reasonable explanation for the observed beneficial effects of MSCs in reducing the frequency of apoptotic cells in the transplanted heart.…”

Vascular Regeneration by Stem/Progenitor Cells

“…59 Because of their easy isolation and relative abundance compared with other kinds of mesenchymal stem cells, adipose tissue stromal cells have recently become a popular cell type for stem cell research. 60 Injection of allogeneic abdominal adipose-derived stem cells, either with or without transfection with plasmid-VEGF165, has been shown to provide a protective role in a rabbit model of critical hind limb ischemia. These adiposederived stem cells increased arteriolar density and protection against ischemia-induced muscle lesions.…”

Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine

“…The cardioprotective properties of HO-1 were evaluated in studies conducted on the HO-1-overexpressing BM- [167] and ASCs [168] delivered to injured cardiac tissue.…”

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