Injury-induced fetal reprogramming imparts multipotency and reparative properties to pericardial adipose stem cells

Abstract

Background: Injury may induce a sequential activation of intrinsic reparative activity that supports the maintenance of tissue homeostasis.

Method: In 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 (WT1^pos) isolated MI Wistar rats with an intact pericardial sac in which cardiac transudate was accumulated, sampled, and analyzed.

Results: The WT1^pos cells formed colony-like aggregates in culture that subsequently generated phase-bright cells that homogenously constituted WT1 expression (> 98%). The WT1^pos 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 WT1^pos cells promoted regional angiogenesis and myogenesis which led to significant functional amelioration of the infarcted hearts. Furthermore, we demonstrated that WT1^pos cells uniquely secreted hepatocyte growth factor (HGF) as a key antiapoptotic factor that promotes cardiac repair.

Conclusion: Injury-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.

Keywords: Angiogenesis; Apoptosis; Hepatocyte growth factor (HGF); Pericardial adipose stem cells (pADSC); Pericardial fluid; Wilms’ tumor factor 1 (WT1).