Rehabilitative Interventions for Rejuvenating the Regenerative Potential of Skeletal Muscle

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）是否移植到宿主体内 肌肉通过一种新的微创肌肉嵌入（MIME）技术可以促进供体来源的 肌生成我们的研究也将评估在神经肌肉电刺激和有力的离心肌肉 收缩可以增强供体来源的肌生成。我们将在免疫缺陷的NSG中进行研究- GFP小鼠不仅由于免疫排斥风险低而成为移植研究的良好宿主， 还因为它们在所有细胞中表达一种绿色荧光蛋白（GFP）报告基因， 在宿主（GFP（+））和供体来源的（GFP（-））肌纤维之间进行区分。我们将评估捐赠者 通过组织学研究以及生理学研究来研究肌生成。如果成功的话，我们的研究 在治疗由肌肉疾病和创伤引起的肌肉损失中具有显著的转化影响。我们 这项研究也为一项新的研究铺平了道路，该研究将利用尸体肌肉作为一种来源。 肌原细胞;提供了重要的见解，以增加肌生成所需的肌肉活动种类 从含有肌原细胞的生物工程肌肉中提取;并且，还有助于开发 人类肌肉疾病，其中将人类肌肉移植到小鼠中是选择的方法。

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.