P2: MYOGENIC POTENTIAL OF BONE MARROW CELLS

P2：骨髓细胞的生肌潜能

• 批准号: 7725248
• 负责人: MEHRDAD ABEDI
• 金额: $ 24.1万
• 依托单位: ROGER WILLIAMS HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725248
• 关键词: Bone Marrow Cells; Cell Count; Cell Transplants; Cells; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Desmin; Direct Lytic Factors; Event; Frequencies; Funding; Grant; Green Fluorescent Proteins; Infusion procedures; Injection of therapeutic agent; Injury; Institution; Lead; Marrow; Mus; Muscle; Muscle Cells; Muscle Fibers; Nature; Numbers; Population; Radiation; Rate; Research; Research Personnel; Resources; Skeletal muscle injury; Source; Time; Transplantation; Treatment Protocols; United States National Institutes of Health; cell type; in vivo; transdifferentiation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Conversion of green-fluorescent protein (GFP) positive marrow cells to skeletal muscle cells has been demonstrated and is the focus of this project. We have determined that donor GFP+ marrow cells have converted to muscle cells by colocalizing GFP and desmin in morphologically characteristic muscle fibers. We have found increasing levels of marrow conversion or transdifferentiation to skeletal muscle cells by altering the specifics of the transplant regimen including cell number, timing of transplant and mode of cell delivery (i.e. local injection vs systemic infusion or mobilization of transplanted cells). We have also found that the number of conversion events changes with different mobilization regimens and that subsets of marrow cells, give higher rates of conversion than unseparated marrow cells. The nature of the skeletal muscle injury, radiation or direct cardiotoxin injection, is also critical in determining the level of transdifferentiation of marrow to muscle cells seen in vivo. In preliminary studies using a cardiotoxin muscle injury in previously transplanted mice, combined with radiation and direct injection of different populations of marrow cells we have obtained conversion rates up to12%, i.e. 12% of the muscle fibers were GFP+ skeletal muscle cells. This project evaluates the specifics of muscle injury which will lead to high-level conversion of marrow to muscle and to explore which particular cell type can give rise to muscle at the highest frequency, the timing of transplant suitable for such conversions and the number of cells necessary to obtain significant muscle conversion.

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