Injury-induced fetal reprogramming imparts multipotency and reparative properties to pericardial adipose stem cells.
Injury-induced fetal reprogramming imparts multipotency and reparative properties to pericardial adipose stem cells.
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损伤诱导的胎儿重编程赋予心包脂肪干细胞多能性和修复特性
DOI：
10.1186/s13287-018-0959-1
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发表时间：
2018-08-13
影响因子：
7.5
通讯作者：
Ding Z
中科院分区：
文献类型：
--
作者：
Tang J;Wang X;Tan K;Zhu H;Zhang Y;Ouyang W;Liu X;Ding Z
损伤可能会诱导内在修复活性的连续激活，从而支持组织稳态的维持。在本实验中，我们研究了心肌梗死 (MI) 是否能够恢复维尔姆斯肿瘤因子 1 (WT1) 的表达，作为心包脂肪干细胞 (pADSC) 中胎儿重编程的关键标志。我们对表达 WT1 的 pADSC (WT1pos) 分离的 MI Wistar 大鼠的免疫表型标志物、心脏电位和修复活性进行了表征，这些大鼠具有完整的心包囊，其中积累了心脏漏出液，进行了采样和分析。 WT1pos 细胞在培养物中形成集落样聚集体，随后产生均质地构成 WT1 表达的相亮细胞 (> 98%)。 WT1pos 细胞与典型的 pADSC 具有相同的表面标记，但在特定条件下增强了心脏发生（isl-1、gata-4、Sox2 和 Tbx18）以及心脏定向（内皮细胞：28%；心肌原性：12.3%）的转录本。值得注意的是，WT1pos细胞的心脏移植促进了局部血管生成和肌生成，从而导致梗塞心脏的功能显着改善。此外，我们证明 WT1pos 细胞独特地分泌肝细胞生长因子（HGF）作为促进心脏修复的关键抗凋亡因子。 pADSC 中与损伤相关的胎儿重编程促进心脏分化，并通过增强 HGF 的产生来促进修复活动。因此，损伤“条件化”的 pADSC 可能代表来自梗死患者的有用的自体细胞供体，用于基于细胞的治疗。
Injury may induce a sequential activation of intrinsic reparative activity that supports the maintenance of tissue homeostasis. 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 (WT1pos) isolated MI Wistar rats with an intact pericardial sac in which cardiac transudate was accumulated, sampled, and analyzed. The 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. 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.
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影响因子：
4.5
作者：
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通讯作者：
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