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Studying the diversity and epigenetic states of cardiac stem cells after ageing and rejuvenation

研究衰老和返老还童后心脏干细胞的多样性和表观遗传状态

基本信息

批准号：
269002191
负责人：
Dr. Katharina Wystub-Lis
金额：
--
依托单位：
The Victor Chang Cardiac Research Institute
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/269002191?language=en
关键词：
Studying diversity epigenetic states cardiac

项目摘要

The degree of cardiomyocyte (CM) turnover in the mammalian heart has been controversial although most workers now agree that there is only a very low level of CM replacement during aging and after injury. The origin of new CMs is still unclear, with different studies highlighting potential for proliferation of existing CMs as well stem cell deployment. Stem cell or rejuvenation therapies that achieve enhanced replacement of myocardium and vascular tissue in the wake of ischemic injury would be of enormous benefit to humanity. The Harvey group has previously described a population of colony-forming cells that reside within the CM interstitium and adventitia of coronary arteries in young adult mouse hearts. These cells form mesenchymal stem/stromal cell (MSC)-like cultures akin to those originally described in bone marrow (BM). We hypothesise that cardiac MSC-like cells are a stem cell type analogous to those in BM but with distinct origins and functionalities. We propose that they are dedicated to cardiac homeostasis and repair, acting as a reserve for multiple cell types in the heart, including CMs. They likely additionally act as stress sensors to support CM, vascular tissue and perhaps other stem cell populations through dedicated paracrine functions. The work proposed in this grant addresses the concept of stem cell rejuvenation in aged and compromised tissues. It seeks to understand the diversity and fate of cardiac stem cells in vivo and will explore the epigenetic changes that occur with ageing and stem cell rejuvenation.

哺乳动物心脏中心肌细胞（CM）更新的程度一直存在争议，尽管大多数工作者现在同意在衰老和损伤后只有非常低水平的CM替换。新CM的起源仍不清楚，不同的研究强调了现有CM增殖以及干细胞部署的潜力。干细胞或再生疗法，实现增强心肌和血管组织在缺血性损伤后的替代将是人类的巨大利益。Harvey小组先前描述了年轻成年小鼠心脏中冠状动脉的CM内膜和外膜内存在的集落形成细胞群。这些细胞形成类似于最初在骨髓（BM）中描述的那些的间充质干细胞/基质细胞（MSC）样培养物。我们假设心脏MSC样细胞是一种干细胞类型，类似于BM中的干细胞，但具有不同的起源和功能。我们认为它们致力于心脏的稳态和修复，作为心脏中多种细胞类型的储备，包括CM。它们可能还作为压力传感器，通过专门的旁分泌功能支持CM，血管组织和其他干细胞群。这项资助提出的工作解决了衰老和受损组织中干细胞再生的概念。它旨在了解体内心脏干细胞的多样性和命运，并将探索随着衰老和干细胞再生而发生的表观遗传变化。