Mesenchymal stem cells (MSC) are not universal and may be subject to dynamic changes upon local milieus in vivo and after isolation and cultivation in vitro. Here, we demonstrate that MSC derived from murine pericardial adipose tissue (pMSC) constitute two cohorts of population distinguished by the level of CD73 expression (termed as CD73high and CD73low pMSC). Transplantation of two types of cells into mouse hearts after myocardial infarction (MI) revealed that the CD73high pMSC preferentially brought about structural and functional repair in comparison to the PBS control and CD73low pMSC. Furthermore, the CD73high pMSC displayed a pronounced anti-inflammatory activity by attenuating CCR2+ macrophage infiltration and upregulating several anti-inflammatory genes 5 days after in vivo transplantation and ex vivo cocultivation with peritoneal macrophages. The immunomodulatory effect was not seen in cocultivation experiments with pMSC derived from CD73 knockout mice (CD73-/-) but was partially blocked by pretreatment of the A2b receptor antagonist, PSB603. The results highlight a heterogeneity of the CD73 expression that may be related to its catalytic products on the modulation of the local immune response and thus provide a possible explanation to the inconsistency of the regenerative results when different sources of donor cells were used in stem cell-based therapy.
Spatial segregation is one of the most important mechanisms that facilitates coexistence among competing species. Large populations of two introduced and congeneric goby species (Rhinogobius giurinus and Rhinogobius cliffordpopei) now co-occur in Lake Erhai, a plateau lake in the Yunnan-Guizhou Plateau (China). Herein we quantified the spatio-temporal distribution of the two species to determine whether spatial segregation occurred within the same ecosystem. A total of 67,819 individuals of R. giurinus and 36,043 of R. cliffordpopei were sampled across four seasons. The results indicated that R. giurinus mostly occupied profundal habitat (PH) while R. cliffordpopei mainly used littoral habitat (LH). Correlation analysis revealed the abundance of R. giurinus was positively associated with deep water, silt and coarse sand substrata, whereas the distribution of R. cliffordpopei was positively associated with high densities of macrozooplanktons and high abundances of other fish species, high concentration of dissolved oxygen and high densities of submerged macrophytes. Except in spring, the body condition of R. giurinus was significantly higher in the PH than in the LH. The body condition of R. cliffordpopei did not differ significantly between habitats in the four seasons. These findings demonstrate that the two congeneric and introduced goby species occupy distinct habitats, indicating that spatial segregation enables coexistence of the two invasive species at high abundances within an ecosystem.
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.
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