The Origin of Human Mesenchymal Stromal Cells Dictates Their Reparative Properties

Abstract

BackgroundHuman mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest in regard to cell‐based therapies. We aimed to test the hypothesis that hMSCs from the heart and epicardial fat would be better cells for infarct repair.Methods and ResultsWe isolated and grew hMSCs from patients with ischemic heart disease from 4 locations: epicardial fat, pericardial fat, subcutaneous fat, and the right atrium. Significantly, hMSCs from the right atrium and epicardial fat secreted the highest amounts of trophic and inflammatory cytokines, while hMSCs from pericardial and subcutaneous fat secreted the lowest. Relative expression of inflammation‐ and fibrosis‐related genes was considerably higher in hMSCs from the right atrium and epicardial fat than in subcutaneous fat hMSCs. To determine the functional effects of hMSCs, we allocated rats to hMSC transplantation 7 days after myocardial infarction. Atrial hMSCs induced greatest infarct vascularization as well as highest inflammation score 27 days after transplantation. Surprisingly, cardiac dysfunction was worst after transplantation of hMSCs from atrium and epicardial fat and minimal after transplantation of hMSCs from subcutaneous fat. These findings were confirmed by using hMSC transplantation in immunocompromised mice after myocardial infarction. Notably, there was a correlation between tumor necrosis factor‐α secretion from hMSCs and posttransplantation left ventricular remodeling and dysfunction.ConclusionsBecause of their proinflammatory properties, hMSCs from the right atrium and epicardial fat of cardiac patients could impair heart function after myocardial infarction. Our findings might be relevant to autologous mesenchymal stromal cell therapy and development and progression of ischemic heart disease.

Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion, and Fibrotic Burden When Administered to Patients Undergoing Coronary Artery Bypass Grafting

“…From preclinical and translational studies in an acute or subacute ischemic environment, it is known that MSCs act in a multifactorial manner 36-39 . MSCs release anti-fibrotic matrix metaloproteases, modulate cardiac stem cell proliferation and differentiation 9 , stimulate neovascularization 17, 2240 , establish intercellular coupling with cardiomyocytes 41 , mediate Akt-dependant change in calcium and upregulate C×43 42 .…”

Reconstitute the damaged heart via the dual reparative roles of pericardial adipose-derived flk-1+ stem cells

“…The recently developed strategy using multipotent stem cells to substitute the damaged cardiomyocytes has been considered as one of the exciting interventions to ameliorate cardiac contractile function [1,2]. While several laboratories have shown functional benefits with transplantation of stem cells derived from either cardiac [3,4] or extra cardiac sources [5][6][7][8], we have recently demonstrated that the stem cells derived from the pericardial adipose tissue (pADSC) favored myogenic differentiation and yielded efficiently cardiac repair in vivo [9], although the mechanistic basis involved remains unclear [10]. Previous experiments have proved that the stem cell-mediated benefits were mediated by the paracrine effects which may involve in releasing growth factors [11] or microRNA [12] and also likely in horizontal gene transfer [13].…”

“…Previous experiments have proved that the stem cell-mediated benefits were mediated by the paracrine effects which may involve in releasing growth factors [11] or microRNA [12] and also likely in horizontal gene transfer [13]. Therefore, the therapeutic effectiveness largely depends on the type of donor cells injected [7] and their capability of generating adequate trophic factors.…”

Myogenic differentiation and reparative activity of stromal cells derived from pericardial adipose in comparison to subcutaneous origin

“…The cell source-related heterogeneity may not only be related to cell proliferation, clonogenicity, and the potential to differentiate, but also may greatly affect the survivability and behavior after being transplanted into the hostile environment of ischemia, inflammation, proapoptotic factors, and scarring from myocardial infarction [3, 6]. Recently, Naftali-Shani et al .…”