Stem cell biology in cardiovascular regeneration

心血管疾病，主要是心脏病和中风，是发达国家所有种族和族裔群体中男女死亡的主要原因。对发展中国家来说，这也是一个日益严重的问题。每年约有100万美国人死于心血管疾病，约占总死亡人数的42%。心血管疾病的并发症往往导致长？长期而言，生活质量严重下降。受损心脏的愈合能力有限，心肌梗死后新血管的生长能力有限，这是这些长期并发症，特别是心力衰竭的主要原因。我们的实验室主要研究干细胞在心血管再生中的作用。我们正在从成人骨髓中分离罕见的干细胞群。这些被称为多能成体祖细胞（MAPCs）的细胞代表了间充质基质细胞（MSC）的一个亚群，但具有能够分化成几乎所有身体组织的独特特性。当这些MAPCs被注射到发育中的小鼠胚胎中时，它们有助于形成所有器官结构（除了种系）特性，这些特性使它们与胚胎干细胞相似，只是它们来自成人而不是胚胎。我们正在研究MAPCs分化为内皮细胞和平滑肌细胞（正常血管中的主要细胞群）以及心肌细胞的分子机制。目前，我们正在大鼠和小鼠损伤模型中测试具有特征的MAPCs。我们建立了大鼠后肢缺血模型，并对不同类型干细胞（MAPC、MSC和ES-cell）改善后肢缺血灌注和功能的能力进行了测试和比较。了解干细胞的功能，包括分子和细胞途径，对于设计和开发心血管疾病的新疗法至关重要。我们预计，通过更好地了解这些成体干细胞的生物学特性及其在心脏再生中的作用，可能会开发出新的治疗干预措施，以改善许多患有慢性心脏病的患者的预后。

Cardiovascular disease (CVD), principally heart disease and stroke, is the leading cause of death for both men and women, among all racial and ethnic groups in developed countries. It is also an increasing problem for developing countries. Almost 1 million Americans die of CVD each year, which is approximately 42% of all deaths. Complications of CVD often results in a long?term, severe reduction in quality of life. The limited ability of the damaged heart to heal, and of new blood vessels to grow after myocardial infarction are the main reasons for these long term complications, specifically of heart failure. Our laboratory focuses on the role of stem cells in cardiovascular regeneration. We are isolating rare stem cell populations from the bone marrow of adults. These cells called Multipotent Adult Progenitor Cells (MAPCs) represent a subpopulation of Mesenchymal Stromal Cells (MSC) but have the unique properties of being able to differentiate into almost all tissues of the body. When these MAPCs are injected into a developing mouse embryo, they contribute to all organ structures (except the germ line) properties that make them similar to embryonic stem cells except that they are derived from adults, not embryos. We are investigating the molecular mechanisms that enable MAPCs to differentiate into endothelial and smooth muscle cells, the major cell populations found in normal blood vessel, as well as cardiomyocytes. At present we are testing characterized MAPCs in rat and mouse injury models. We have developed a hind limb ischemia model in rats and are testing and comparing different stem cell types (MAPC, MSC and ES-cell) in their ability to improve not only the perfusion but also the function of ischemic hind limbs. Understanding the function including the molecular and cellular pathways of stem cells is critical to the design and development of new therapies for cardiovascular diseases. We anticipate that by better understanding the biology of these adult stem cells and their role in cardiac regeneration, new therapeutic interventions may be developed to improve the outcome of the many patients that suffer from chronic cardiac diseases.