PDF(Pubmed)
Abstract：
Tissue damage often induces local inflammation that in turn dictates a series of subsequential responses, such as stem cell activation and growth, to maintain tissue homeostasis. The aim of the study is to testify the possibility of using inflammation-trained stem cells as optimal donor cells to augment the efficacy of cell therapy. The pericardial stem/stromal cells derived from the animals after myocardial infarction (MI-pSC) showed an enhanced myogenic potential and augmented reparative activity after transplantation in the injured hearts, as compared to the Sham-pSC. Bulk RNA-Seq analysis revealed significant upregulation of a panel of myogenic and trophic genes in the MI-pSC and, notably, Sfrp1 as an important anti-apoptotic factor induced robustly in the MI-pSC. Injection of the MI-pSC yielded measurable numbers of surviving cardiomyocytes (Tunel and Casp-3 negative) within the infarct area, but the effects were significantly diminished by siRNA-based silence of Sfrp1 gene in the pSC. Primed Sham-pSC with pericardial fluid from MI rats mimicked the upregulation of Sfrp1 and enhanced myogenic potential and reparative activity of pSC. Taken together, our results illustrated the inflammation-trained pSC favor a reparative activity through upregulation of Sfrp1 gene that confers anti-apoptotic activity in the injured cardiomyocytes. Therefore, the active form of stem cells may be used as a cardiac protective agent to boost therapeutical potential of stem cells.
摘要：
组织损伤通常会引起局部炎症，进而决定一系列后续反应，如干细胞活化和生长，维持组织稳态.该研究的目的是证明使用经炎症训练的干细胞作为最佳供体细胞来增强细胞疗法功效的可能性。来自心肌梗死后动物的心包干/基质细胞（MI-pSC）在受伤的心脏移植后显示出增强的肌源性潜能和增强的修复活性，与假PSC相比。BulkRNA-Seq分析显示MI-pSC中一组生肌和营养基因的显着上调，特别是,Sfrp1作为重要的抗凋亡因子，在MI-pSC中受到强烈诱导。注射MI-pSC在梗死区域内产生了可测量数量的存活心肌细胞（Tunel和Casp-3阴性）。但是在pSC中基于siRNA的Sfrp1基因沉默的作用显着减弱。MI大鼠心包液引发的Sham-pSC模仿了Sfrp1的上调，并增强了pSC的生肌潜能和修复活性。一起来看,我们的结果表明，经炎症训练的pSC通过上调Sfrp1基因而具有修复活性，从而在受损的心肌细胞中赋予抗凋亡活性。因此,干细胞的活性形式可用作心脏保护剂以增强干细胞的治疗潜力。
