Adult Stem Cell Therapy For Cardiac Failure

成体干细胞治疗心力衰竭

• 批准号: 6671714
• 负责人: NEAL DAVID EPSTEIN
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6671714
• 关键词: bone marrow; cardiovascular disorder therapy; heart failure; heart function; immunologic techniques; laboratory mouse; mature animal; microarray technology; mixed tissue /cell culture; muscle cells; myoblasts; stem cell transplantation; striated muscles; subtraction hybridization; transplant rejection

Heart failure may occur from a variety of causes including ischemic heart disease, toxins, pressure or volume overload. Recovery of cardiac function is hindered by a long known observation that cardiac myocytes do not divide in appreciable numbers during adult life. Physiologic demands for increased cardiac output are met by hypertrophy of existing cardiac myocytes through the formation of additional sarcomeres (the unitary contractile apparatus)within these cells. At the present time, the only remedy for end stage heart failure is cardiac transplant, which is limited by the supply of matched hearts and complicated by the need to suppress immune rejection. We have discovered a previously unknown subpopulation of stem cells in adult murine skeletal muscle that can be transformed into beating cardiomyocytes under primary tissue culture conditions. These cells are not satellite cells, myofibroblasts or myoblasts. A portion of the freshly isolated stem cells, injected into the vein of a mouse with chronic heart failure, will home to the heart and progress along a pathway to cardiac cell differentiation. In addition, we have produced a conditioned media from co-cultured bone-marrow and skeletal muscle cells that shortens the time that it takes the isolated stem cells to differentiate into cardiac myocytes. We are presently using a variety of gene array, genetic subtraction and immunologic techniques to further characterize these cells in order to facilitate the identification of human analogues. If the latter can be identified and isolated, they may be useful for therapeutic intervention in cardiac failure from a variety of causes. This would avoid the problems of immune rejection as well as the supply limitations of organ

心力衰竭可能来自多种原因，包括缺血性心脏病，毒素，压力或体积超负荷。悠久的观察结果阻碍了心脏功能的恢复，即心肌细胞在成人生活中不会有明显的数量分裂。通过在这些细胞中形成其他肉瘤（单一的收缩仪），现有心肌细胞的肥大来满足心脏输出增加的生理需求。目前，终末期心力衰竭的唯一补救措施是心脏移植，这受到匹配心脏的供应的限制，并因抑制免疫排斥的需要而变得复杂。我们已经发现了成年鼠骨骼肌中干细胞的先前未知的亚群，可以转化为在原发性组织培养条件下跳动的心肌细胞。这些细胞不是卫星细胞，肌纤维细胞或成肌细胞。新鲜分离的干细胞的一部分，注射到具有慢性心力衰竭的小鼠静脉中，将回到心脏，并沿着心脏细胞分化的途径进展。此外，我们从共培养的骨髓和骨骼肌细胞中产生了一种条件培养基，该培养基缩短了将其带动分离的干细胞分化为心肌细胞的时间。目前，我们正在使用各种基因阵列，遗传减法和免疫学技术来进一步表征这些细胞，以促进人类类似物的鉴定。如果可以识别和隔离后者，则可能对各种原因的心脏衰竭进行治疗干预。这将避免免疫排斥的问题以及器官的供应限制