Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy.

摘要

Project 1: Dilated cardiomyopathy affects approximately 1 in 2,500 individuals in the United States and is the 3rd most common cause of heart failure and the most frequent cause of heart transplantation. Patients that suffer from various muscle diseases, including Duchenne muscular dystrophy (DMD), develop progressive cardiomyopathy. Cellular cardiomyoplasty, which involves the transplantation of exogenous cells into the heart, is a possible approach by which to repair diseased or injured myocardium and improve cardiac function. Though there are a number of drugs prescribed to treat dilated cardiomyopathy, there is no cure and individuals eventually require a heart transplant; therefore the use of cardiomyoplasty to repair the hearts of individuals suffering from cardiomyopathy could possibly be an effective alternative to heart transplantation. Technical Objective No. 1: To investigate the effect of cell survival, proliferation, and differentiation on the regeneration/repair capacity of various human MDSC populations implanted into the heart of mdx/SCID mice. Technical Objective No. 2: To investigate the role that angiogenesis plays in the regeneration/repair capacity of human MDSCs injected into the hearts of mdx/SCID mice. Project 2: This project will determine the extent to which novel sources of hepatocytes can be used for regeneration and repair of injuries to the liver and liver failure. A more complete understanding of the extent to which donor liver cells can be resuscitated from non-traditional sources and expanded for application to reduce liver injury and toxin and/or cancer risk should enhance the number of areas where hepatic stem cell transplantation might be effectively applied. Technical Objective No. 1: To characterize and expand hepatocytes from patients with cirrhosis and end-stage liver disease in immune deficient hosts whose livers permit extensive repopulation with donor cells.