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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 绿色荧光蛋白（GFP）阳性骨髓细胞向骨骼肌细胞的转化已经得到证实，也是该项目的重点。我们已经确定，通过将 GFP 和结蛋白共定位在形态特征的肌纤维中，供体 GFP+ 骨髓细胞已转化为肌肉细胞。我们发现，通过改变移植方案的细节，包括细胞数量、移植时间和细胞递送方式（即局部注射与全身输注或移植细胞动员），骨髓转化或转分化为骨骼肌细胞的水平不断提高。我们还发现，转化事件的数量随着不同的动员方案而变化，并且骨髓细胞亚群比未分离的骨髓细胞具有更高的转化率。骨骼肌损伤、辐射或直接心脏毒素注射的性质对于确定体内观察到的骨髓向肌肉细胞的转分化水平也至关重要。 在对先前移植的小鼠进行心脏毒素肌肉损伤的初步研究中，结合辐射和直接注射不同群体的骨髓细胞，我们获得了高达 12% 的转化率，即 12% 的肌纤维是 GFP+ 骨骼肌细胞。该项目评估了肌肉损伤的具体情况，这将导致骨髓向肌肉的高水平转化，并探索哪种特定细胞类型可以以最高频率产生肌肉、适合这种转化的移植时机以及细胞数量获得显着的肌肉转化所必需的。