Characterization of vascular progenitor subpopulations for the treatment of ischemic heart disease

项目摘要/摘要 收到这份多样性补充资料将支持我的学生斯特凡·维扎兹，他是萨尔瓦多人(拉丁裔) 血统，在他追求学术医学的职业生涯中。斯特凡去年夏天一直在培养他的技能 分子和细胞生物学，为本科期间的进一步培训做准备。在.期间 学年，他将磨练和应用这些技能，以更好地表征从 脂肪可能会产生功能性血管，作为缺血心肌的天然旁路。这 项目是我建议的目标2的自然延伸，目标2确定了新的生长因子和基质细胞 可能改变组织微环境和提高心肌细胞存活率的亚群 来源于人类诱导的多能干细胞在心肌梗死的缺血模型中。目前还不清楚 我们在目标2中确定的间质亚群是否可以单独治疗。 缺血性心脏病所致的终末期心力衰竭仍然是一种高发病率和高发病率的破坏性疾病。 死亡率。据估计，每九个人中就有一个死于心力衰竭。部分心脏缺血症患者 疾病可以发展侧支循环，即损伤区域的新血管提供自然的 为血流不畅的区域搭桥。目前尚不清楚这些附属物是如何发展的，以及它们在多大程度上 可以保护心肌免受永久性损伤。在本提案中，我们将使用先进的蜂窝和 分子成像技术(例如，流式细胞术、谱系追踪、单细胞测序和小动物 成像研究)以表征从脂肪中分离的间充质细胞亚群 缺血微环境中的功能性血管。如果成功，这些细胞不仅可以用作 辅助治疗为支持IPSC移植，也成为独立治疗提供 侧支循环保护心脏免受损伤。

PROJECT SUMMARY/ABSTRACT Receiving this Diversity supplement will support my student, Stefan Veizades, who is of Salvadorian (Latino) descent, in his pursuit of a career in academic medicine. Stefan has spent the last summer building his skills in molecular and cellular biology in preparation for further training during his undergraduate years. During the academic year, he will hone and apply these skills to better characterize mesenchymal stem cells isolated from fat that potentially generate functional vessels to serve as natural bypasses for the ischemic myocardium. This project is a natural extension of Aim 2 of my proposal, which identifies novel growth factors and stromal cell subpopulations that may modify the tissue microenvironment and improve the survival of cardiomyocytes derived from human induced pluripotent stem cells in an ischemic model of myocardial infarction. It is unclear whether the stromal sub-populations that we identified in Aim 2 can be stand-alone therapy. End-stage heart failure from ischemic heart disease remains a devastating disease with high morbidity and mortality. It is estimated that one in nine death results from heart failure. Some patients with ischemic heart disease can develop collateral circulation, namely, new vessels in the area of injury that provide natural bypasses for areas of poor blood flow. It remains unclear how these collaterals develop and to what extent they can protect the myocardium from permanent damage. In this proposal, we will use advanced cellular and molecular imaging techniques (e.g., flow cytometry, lineage tracing, single cell sequencing, and small animal imaging studies) to characterize subpopulations of mesenchymal cells isolated from fat that can produce functional vessels in the ischemic microenvironment. If successful, these cells can serve not only serve as adjuvant therapy for supporting the transplantation of iPSC, but also become stand-alone therapy to provide collateral circulation to protect hearts from damage.