Rehabilitative Interventions for Rejuvenating the Regenerative Potential of Skeletal Muscle

恢复骨骼肌再生潜力的康复干预措施

基本信息

批准号：
9299064
负责人：
Joseph Antonio Roche
金额：
$ 7.7万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9299064
关键词：
Activities of Daily Living Affect Aging Autopsy Biomedical Engineering Biopsy Breathing Cadaver Cell Therapy Cells Complement Data Exercise Fiber Frequencies Future Goals Green Fluorescent Proteins Human Immune Implant Injectable Intervention Metabolic Mitotic Mouse Protein Mus Muscle Muscle Contraction Muscle Fibers Muscle function Muscular Atrophy Myoblasts Myopathy Natural regeneration Operative Surgical Procedures Outcome Physiological Rehabilitation therapy Reporter Research Risk Role Skeletal Muscle Source Structure Techniques Testing Therapeutic Tissue Donors Tissue Grafts Tissue Harvesting Tissues Transplantation Trauma Work animal model development base effective therapy exercise intensity histological studies implantation improved improved functioning insight mechanical force minimally invasive muscle form muscle regeneration myogenesis neuromuscular activity neuromuscular stimulation novel regenerative satellite cell skeletal success therapy outcome translational impact

项目摘要

Project Summary Our studies will assess if donor skeletal muscle tissue (from human cadavers and mice) transplanted into host muscle through a novel Minimally Invasive Muscle Embedding (MIME) technique can promote donor-derived myogenesis. Our studies will also assess in neuromuscular electrical stimulation and forceful eccentric muscle contractions can enhance donor-derived myogenesis. We will perform our studies in immunodeficient NSG- GFP mice, which are not only good hosts for transplantation studies due to the low risk of immune rejection, but also because they express a green fluorescent protein (GFP) reporter in all their cells, making it easy to differentiate between host (GFP(+)) and donor-derived (GFP(-)) muscle fibers. We will assess donor-derived myogenesis through histological studies as well as physiological studies. If successful, our studies could have significant translational impact in the treatment of muscle loss arising from muscle disease and trauma. Our studies could also pave the way for a new line of research looking into the use of cadaveric muscle as a source of myogenic cells; provide important insights into the kinds of muscle activity needed to increase myogenesis from bioengineered muscle containing myogenic cells; and, also help in the development of animal models of human muscle disease where transplantation of human muscle into mouse is the approach of choice.

项目摘要我们的研究将评估供体骨骼肌组织（来自人尸体和小鼠）是否被移植到宿主通过新颖的微创肌肉嵌入（MIME）技术可以促进供体来源的肌肉肌发生。我们的研究还将评估神经肌肉电刺激和有力的偏心肌肉收缩可以增强供体衍生的肌发生。我们将进行免疫缺陷型NSG-的研究 GFP小鼠，由于免疫排斥的风险低，这不仅是用于移植研究的好宿主，而且是而且还因为它们在其所有细胞中表达绿色荧光蛋白（GFP）记者，因此很容易区分宿主（GFP（+））和供体衍生（GFP（ - ））肌肉纤维。我们将评估捐助者的衍生通过组织学研究和生理研究通过肌发生。如果成功的话，我们的研究可能会有肌肉疾病和创伤引起的肌肉损失的重大翻译影响。我们的研究还可以为新的研究系列铺平道路，以利用尸体肌肉作为来源肌源性细胞；提供有关增加肌发生所需的肌肉活动的重要见解来自含有肌原细胞的生物工程肌肉；并且，也有助于发展动物模型人类肌肉疾病，其中人类肌肉向小鼠移植是选择的方法。