Soluble Motogens and Chemoattractants from Damaged Muscle

受损肌肉中的可溶性促动力剂和化学引诱剂

• 批准号: 8500217
• 负责人: Dawn D Cornelison
• 金额: $ 15.66万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8500217
• 关键词: Acute; Address; Adult; Affinity; Algorithms; Area; Basic Science; Biological Assay; CXCL12 gene; Cell Therapy; Cells; Cellular biology; Charge; Chemotactic Factors; Chemotaxis; Clinical; Collaborations; Commit; Complex; Cues; Data; Data Set; Development; Disease; Distal; Duchenne muscular dystrophy; Endogenous Factors; Engraftment; Environment; Failure; Gel Chromatography; Goals; Heparin; Hepatocyte Growth Factor; Home environment; Homing; Human; In Vitro; Injection of therapeutic agent; Injury; Investigation; Ion-Exchange Chromatography Procedure; Literature; Locomotion; Maintenance; Measures; Mediating; Mediator of activation protein; Messenger RNA; Methods; Movement; Muscle; Muscle Cells; Muscle Fibers; Muscle satellite cell; Muscular Dystrophies; Myoblasts; Myopathy; Natural regeneration; Nature; Physiological; Play; Population; Positioning Attribute; Posture; Procedures; Process; Proliferating; Proteins; Proteomics; Protocols documentation; Publishing; Quality of life; Recruitment Activity; Regulation; Research Personnel; Respiration; Role; Sampling; Serum; Signal Pathway; Signal Transduction; Site; Skeletal Muscle; Software Tools; Speed; Stem Cell Development; Stem cells; Stromal Cell-Derived Factor 1; Surveys; System; Techniques; Testing; Therapeutic; Time; Tissues; Work; adult stem cell; cell motility; cell type; chemokine; human disease; improved; in vivo; injured; insight; interest; liquid chromatography mass spectroscopy; meetings; muscle hypertrophy; muscle regeneration; myogenesis; receptor; regenerative; release factor; repaired; research study; satellite cell; success; therapeutic effectiveness; working group

DESCRIPTION (provided by applicant): Skeletal muscle provides the contractile force necessary for not only locomotion but also maintenance of posture and respiration. Diseases that weaken or damage skeletal muscle therefore decrease not only quality of life but are, in cases such as Duchenne's muscular dystrophy, fatal. Differentiated muscle cells are terminally postmitotic and cannot generate new myonuclei to replace those lost to damage or disease; a population of adult stem cells termed satellite cells serves to supply new committed muscle cells for muscle hypertrophy, repair, and regeneration. Satellite cells are distributed throughout the muscle and it is well- established that if they are within an area of muscle that is damaged they will activate from their usual quiescent state and proliferate to form a pool of replacement myoblasts, which will differentiate into new muscle fibers or fuse with damaged ones to rapidly and effectively repair the muscle damage. An area of increasing interest is the potential for satellite cells distal to an area of damage to be recruited and relocated through cell migration; this would enhance the efficiency of satellite cell-mediated muscle regeneration. Therapeutic engraftments studies in which satellite cells are injected into dystrophic muscle have met with little success, and one reason has been a failure of injected cells to spread and efficiently engraft. The experiments we propose will explore the ability of factors released by damaged muscle either to promote general motility of satellite cells or to stimulate homing of satellite cels to a specific area; these studies are necessary to define the number and nature of the factors that would require further in-depth study in a later proposal. An understanding of the capacity of satellite cells to move and relocate in vivo, and the role those two activities play in muscle regeneration, would therefore add not only to basic understanding of muscle regeneration but also impact clinical therapies for DMD and other muscle diseases. In the course of these experiments, we are also working towards improved methods for automated tracking of cells in culture, in collaboration with Dr. Kanappan Palaniappan. We will produce an extremely large dataset of tracked cells, which is necessary to develop algorithms capable of replicating tracking choices made by a human researcher. Given the dramatic increase in both video data in multiple contexts and interest in cell motility in this and other systems, software tools that can accurately detect and track changes in position in a complex, high-background environment will be useful to many groups working in stem cells, development, and cell biology.

描述（由申请人提供）：骨骼肌不仅提供运动所需的收缩力，还提供维持姿势和呼吸所需的收缩力。因此，削弱或损害骨骼肌的疾病不仅会降低生活质量，而且在杜兴氏肌营养不良症等情况下甚至是致命的。分化的肌肉细胞处于有丝分裂末期，不能产生新的肌核来替代因损伤或疾病而丢失的肌核；称为卫星细胞的成体干细胞群可以为肌肉肥大、修复和再生提供新的定向肌肉细胞。卫星细胞分布在整个肌肉中，并且众所周知，如果它们位于受损的肌肉区域内，它们将从通常的静止状态激活并增殖，形成替代成肌细胞池，这些成肌细胞将分化成新的肌纤维或与受损肌融合，快速有效修复肌肉损伤。人们越来越感兴趣的一个领域是，远离损伤区域的卫星细胞有可能通过细胞迁移被招募和重新定位。这将提高卫星细胞介导的肌肉再生的效率。将卫星细胞注射到营养不良的肌肉中的治疗性移植研究收效甚微，原因之一是注射的细胞未能扩散和有效移植。我们提出的实验将探索受损肌肉释放的因子促进卫星细胞总体运动或刺激卫星细胞归巢到特定区域的能力；这些研究对于确定需要在以后的提案中进一步深入研究的因素的数量和性质是必要的。因此，了解卫星细胞在体内移动和重新定位的能力，以及这两种活动在肌肉再生中发挥的作用，不仅会增加对肌肉再生的基本了解，还会影响 DMD 和其他肌肉疾病的临床治疗。 在这些实验过程中，我们还与 Kanappan Palaniappan 博士合作，致力于改进自动跟踪培养细胞的方法。我们将生成一个非常大的跟踪细胞数据集，这是开发能够复制人类研究人员所做的跟踪选择的算法所必需的。鉴于多种环境中视频数据的急剧增加以及对这个系统和其他系统中细胞运动的兴趣，能够准确检测和跟踪复杂、高背景环境中位置变化的软件工具将对干细胞研究中的许多团队有用。细胞、发育和细胞生物学。