Abstract
BackgroundInjury may induce a sequential activation of intrinsic reparative activity that supports the maintenance of tissue homeostasis.MethodIn the present experiments, we investigated whether myocardial infarction (MI) was able to reinstate the expression of Wilms’ tumor factor 1 (WT1) as a key hallmark of fetal reprograming in the pericardial adipose-derived stem cells (pADSC). We characterized the immunophenotypical markers, cardiac potential, and reparative activity of WT1-expressing pADSC (WT1pos) isolated MI Wistar rats with an intact pericardial sac in which cardiac transudate was accumulated, sampled, and analyzed.ResultsThe WT1pos cells formed colony-like aggregates in culture that subsequently generated phase-bright cells that homogenously constituted WT1 expression (> 98%). The WT1pos cells shared identical surface markers with canonical pADSC, but enhanced transcripts for cardiogenesis (isl-1, gata-4, Sox2 and Tbx18) as well as cardiac commitment (endothelial: 28%; cardiomyogenic: 12.3%) in defined conditions. Remarkably, cardiac transplantation of WT1pos cells promoted regional angiogenesis and myogenesis which led to significant functional amelioration of the infarcted hearts. Furthermore, we demonstrated that WT1pos cells uniquely secreted hepatocyte growth factor (HGF) as a key antiapoptotic factor that promotes cardiac repair.ConclusionInjury-associated fetal reprogramming in pADSC facilitates cardiac differentiation and promotes the reparative activity by enhancing HGF production. As such, injury-“conditioned” pADSC may represent a useful autologous cell donor from infarcted patients for cell-based therapy.
Highlights
Injury may induce a sequential activation of intrinsic reparative activity that supports the maintenance of tissue homeostasis
Injury-associated fetal reprogramming in pericardial adipose-derived stem cells (pADSC) facilitates cardiac differentiation and promotes the reparative activity by enhancing hepatocyte growth factor (HGF) production
Reactivation of Wilms’ tumor factor 1 (WT1) expression in pericardial adipose tissue after ischemic injury During tissue preparation for the isolation of pADSC from the myocardial infarction (MI) rats, we found that the pericardial adipose tissue was located mainly in the anterior part of the fibrous layer of the pericardium and, sometimes, adhered to the heart surface after ischemic injury
Summary
Injury may induce a sequential activation of intrinsic reparative activity that supports the maintenance of tissue homeostasis. The epicardial stem cells can be isolated and expanded in vitro and favor a myogenic differentiation and, when transplanted into the infarcted heart in vivo, yield more effective cardiac repair in comparison with cells from subcutaneous fat [12]. It remains elusive whether the pericardial progenitors residing in the pericardial tissue could recapitulate an embryonic program in response to cardiac injury [8]. This question is of practical interest since pericardial adipose tissue is abundant and clinically easy to access, and the re-activated pericardial adipose-derived stem cells (pADSC) may represent one of the most suitable cell donors for cell-based therapy for cardiac ischemic disease [13]
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