Harnessing Adult Stem Cells for Cardiac Regeneration

描述（由申请人提供）：我们对干细胞生物学的理解，特别是在其用于治疗性心血管再生方面，一直在以惊人的速度继续。在过去的几年里，内源性心脏干细胞的鉴定提高了利用这些细胞进行心脏修复的可能性。最近，我们的实验室已经观察到心脏祖细胞群体的存在。这些所谓的心脏侧群（CSP）细胞，在成人心脏中通过其独特的Hoechst染料流出模式鉴定，代表了一种独特的心脏祖细胞群，能够通过与成人心肌细胞偶联介导的过程进行生物化学和更重要的功能性心肌分化。此外，在心肌梗死（MI）后，CSP细胞被急性耗尽，并通过内源性CSP细胞的自我更新和心外骨髓来源的侧群（BMSP）干细胞的归巢而恢复。BMSP归巢至损伤的心脏后，采用类似于内源性CSP细胞的免疫表型。因此，利用体外和体内方法学的多学科方法，本提案的主要目标是描绘调节CSP细胞增殖和分化的信号传导途径。此外，我们将确定BMSP细胞归巢到受损心肌的功能意义，最终目标是利用这些成体干细胞进行生理学意义上的心脏再生。

DESCRIPTION (provided by applicant): Our understanding of stem cell biology, especially in regards to its use for therapeutic cardiovascular regeneration, has continued at a staggering pace. Over the past few years, the identification of endogenous cardiac stem cells has raised the exciting possibility of harnessing these cells for cardiac repair. Recently, our laboratory has observed the existence of a cardiac progenitor cell population. These so termed cardiac side-population (CSP) cells, identified in adult hearts by their distinct Hoechst dye efflux pattern, represent a distinct cardiac progenitor cell population, capable of both biochemical and, more importantly, functional cardiomyogenic differentiation through a process mediated by coupling with adult cardiomyocytes. Moreover, after myocardial infarction (Ml), CSP cells are acutely depleted, and are restored through self-renewal of endogenous CSP cells and homing of extra-cardiac bone marrow-derived side population (BMSP) stem cells. Following homing to the injured hearts, BMSP adopt an immunophenotype similar to endogenous CSP cells. As such, utilizing a multidisciplinary approach of in-vitro and in-vivo methodologies, the main goal of this proposal is to delineate the signaling pathways regulating the proliferation and differentiation of CSP cells. Additionally, we will determine the functional significance of BMSP cell homing to injured myocardium, with the ultimate goal of harnessing these adult stem cells for physiologically significant cardiac regeneration.