首页> 外文期刊>EBioMedicine >p53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivo
【24h】

p53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivo

机译:p53调节体内和体外糖尿病人心脏祖细胞的命运

获取原文
           

摘要

p53 is an important modulator of stem cell fate, but its role in cardiac progenitor cells (CPCs) is unknown. Here, we tested the effects of a single extra-copy of p53 on the function of CPCs in the presence of oxidative stress mediated by doxorubicin in vitro and type-1 diabetes in vivo. CPCs were obtained from super-p53 transgenic mice (p53-tg), in which the additional allele is regulated in a manner similar to the endogenous protein. Old CPCs with increased p53 dosage showed a superior ability to sustain oxidative stress, repair DNA damage and restore cell division. With doxorubicin, a larger fraction of CPCs carrying an extra-copy of the p53 allele recruited @cH2A.X reestablishing DNA integrity. Enhanced p53 expression resulted in a superior tolerance to oxidative stress in vivo by providing CPCs with defense mechanisms necessary to survive in the milieu of the diabetic heart; they engrafted in regions of tissue injury and in three days acquired the cardiomyocyte phenotype. The biological advantage provided by the increased dosage of p53 in CPCs suggests that this genetic strategy may be translated to humans to increase cellular engraftment and growth, critical determinants of successful cell therapy for the failing heart.
机译:p53是干细胞命运的重要调节剂,但其在心脏祖细胞(CPC)中的作用尚不清楚。在这里,我们测试了在体外由阿霉素和体内1型糖尿病介导的氧化应激存在下,p53单拷贝对CPC功能的影响。 CPC从超级p53转基因小鼠(p53-tg)获得,其中其他等位基因的调控方式与内源蛋白相似。 p53剂量增加的旧CPC表现出了较强的维持氧化应激,修复DNA损伤和恢复细胞分裂的能力。对于阿霉素,募集了@ cH2A.X的大部分携带p53等位基因额外拷贝的CPC可以重新建立DNA完整性。通过为CPC提供在糖尿病心脏环境中生存所必需的防御机制,增强的p53表达导致了对体内氧化应激的优异耐受性;他们植入了组织损伤区域,并在三天内获得了心肌细胞表型。 CPC中p53剂量增加所提供的生物学优势表明,这种遗传策略可能会转化为人类,以增加细胞植入和生长,这是心脏衰竭患者成功进行细胞治疗的关键决定因素。

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号