Core 1: Muscular Dystrophy Cell and Serum Banking Core

肌萎缩症细胞系和血清库核心

Muscular Dystrophy Cell Line and Serum Banking Core ABSTRACT The over-arching theme for this P50 CORT grant application is to accelerate the translation of novel genetic therapies from the bench into the clinic. A significant bottleneck in studying pathogenic variants or their correction in the various muscular dystrophies is the limiting factor of a muscle cell model system using patient derived myocytes. The proliferative capacity of muscle cells from muscular dystrophy patients is limited, and the process to obtain cells (muscle biopsy) is invasive. A technique using lentiviral vectors for both hTERT and MyoD delivery to the fibroblasts to create myogenic fibroblasts (hereafter called FibroMyoD) will overcome this bottleneck. The overall objective of the Muscular Dystrophy Cell Line and Serum Banking Core (MD-CLSB Core) will be preparing and banking human primary and immortalized cell lines that will support each of the CORT Projects, as well as for serum and plasma banking for exploratory and collaborative projects. The overall objective will be addressed in three specific aims. Aim 1 will create a unique cell line resource from muscular dystrophy subjects by banking dermal fibroblasts, obtained by skin biopsy, and creating FibroMyoD cell lines. Aim 2 will establish a serum biobank resource, through banking of samples obtained from clinic patients and research subjects, and make these samples available to CORT and external affiliated investigators for hypothesis-driven and discovery research. Finally, in Aim 3, we will develop an improved transdifferentiation protocol to generate mature myofibers from the FibroMyoD lines that more closely mimic mature myofibers. This MD-CLSB Core will leverage the existing expertise of the Nationwide Children's Hospital (NCH) Research Institute Cell Line Core, directed by Kim L. McBride, MD. This institutionally-supported shared resource has been creating and banking cell lines for nearly 10 years, and for the past three years has created primary fibroblast cell lines for the laboratory of the proposed CORT director, Dr. Kevin Flanigan. The current proposal will involve a greatly increased demand on the existing NCH Cell Line Core, and establishment of the CORT Core will provide the additional resources needed to serve as a resource to both the NCH and the broader muscle research community. The cell lines generated and serum samples stored will be a valuable resource for the projects of the proposed CORT, and the broader muscular dystrophy research community, in direct alignment with the P50 CORT mission.