PDF(Pubmed)
Abstract：
Cellular therapy holds immense promise to remuscularize the damaged myocardium but is practically hindered by limited allogeneic sources of cardiac-committed cells that engraft stably in the recipient heart after transplantation. Here, we demonstrate that the pericardial tissue harbors myogenic stem cells (pSCs) that are activated in response to inflammatory signaling after myocardial infarction (MI). The pSCs derived from the MI rats (MI-pSCs) show in vivo and in vitro cardiac commitment characterized by cardiac-specific Tnnt2 expression and formation of rhythmic contraction in culture. Bulk RNA-seq analysis reveals significant upregulation of a panel of genes related to cardiac/myogenic differentiation, paracrine factors, and extracellular matrix in the activated pSCs compared to the control pSCs (Sham-pSCs). Notably, we define MyoD as a key factor that governs the process of cardiac commitment, as siRNA-mediated MyoD gene silencing results in a significant reduction of myogenic potential. Injection of the cardiac-committed cells into the infarcted rat heart leads to long-term survival and stable engraftment in the recipient myocardium. Therefore, these findings point to pericardial myogenic progenitors as an attractive candidate for cardiac cell-based therapy to remuscularize the damaged myocardium.
摘要：
细胞疗法具有使受损心肌再肌化的巨大希望，但实际上受到移植后稳定移植在受体心脏中的心脏定向细胞的有限同种异体来源的阻碍。这里,我们证明,心包组织含有肌源性干细胞(pSCs),这些细胞在心肌梗死(MI)后响应炎症信号而被激活.源自MI大鼠的pSC(MI-pSC)显示体内和体外心脏定型,其特征在于心脏特异性Tnnt2表达和在培养物中形成节律性收缩。BulkRNA-seq分析揭示了一组与心脏/肌源性分化相关的基因的显着上调，旁分泌因子,和活化pSC中的细胞外基质与对照pSC(Sham-pSC)相比。值得注意的是,我们将MyoD定义为控制心脏承诺过程的关键因素，siRNA介导的MyoD基因沉默导致生肌潜能显著降低。将心脏定向细胞注射到梗塞的大鼠心脏中导致长期存活和在受体心肌中的稳定植入。因此,这些发现表明心包肌源性祖细胞是基于心脏细胞的治疗的一个有吸引力的候选者,可以使受损的心肌再肌化.
