{"title":"Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.","authors":"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","doi":"10.1093/stcltm/szad075","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"137-150"},"PeriodicalIF":5.4000,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872698/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cells Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/stcltm/szad075","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
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.
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.