Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cells Translational Medicine Pub Date : 2024-02-14 DOI:10.1093/stcltm/szad075
Hongtao Zhu, Xueqing Liu, Weili Ouyang, Yingcai Hao, Zheheng Ding, Kezhe Tan, Jianfeng Tang, Jianfeng Zhao, Xiaojun Ding, Zenghui Teng, Xiaoming Deng, Weidong Wu, Zhaoping Ding
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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.

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Sfrp1作为培养修复活性的经训练的心包干细胞中的关键旁分泌因子。
组织损伤通常会诱导局部炎症,进而导致一系列后续反应,如干细胞激活和生长,以维持组织稳态。该研究的目的是证明使用炎症训练的干细胞作为最佳供体细胞以提高细胞治疗效果的可能性。与Sham pSC相比,来自心肌梗死后动物的心包干细胞/基质细胞(MI pSC)在移植到受伤心脏后显示出增强的成肌潜能和增强的修复活性。大量RNA-Seq分析显示,MI pSC中一组肌源性和营养性基因显著上调,特别是Sfrp1作为一种重要的抗凋亡因子在MI pSC强烈诱导。MI pSC的注射在梗死区内产生了可测量数量的存活心肌细胞(Tunel和Casp-3阴性),但pSC中Sfrp1基因基于siRNA的沉默显著减弱了这种影响。用MI大鼠的心包液预处理的Sham pSC模拟了Sfrp1的上调,并增强了pSC的成肌潜能和修复活性。总之,我们的结果表明,炎症训练的pSC有利于通过上调Sfrp1基因的修复活性,从而在受伤的心肌细胞中赋予抗凋亡活性。因此,活性形式的干细胞可以用作心脏保护剂,以提高干细胞的治疗潜力。
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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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