Genetically Engineered Muscle Stem Cell Transplantation for Muscular Dystrophy...

基因工程肌肉干细胞移植治疗肌营养不良症......

基本信息

批准号：
8507146
负责人：
ATSUSHI ASAKURA
金额：
$ 31.27万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8507146
关键词：
Achievement Affect Biopsy Blood Vessels Cell Culture Techniques Cell Differentiation process Cell Therapy Cell Transplants Cells Characteristics Code Complex Data Degenerative Disorder Development Disease Duchenne muscular dystrophy Dystrophin Engraftment Epigenetic Process Failure Fibroblasts Generations Genes Genetic Genetic Engineering Goals Homing Homologous Gene Human Immune Immune system In Vitro Individual Injection of therapeutic agent Lead Light Mechanics Memory Methods Modification Mus Muscle Muscle Contraction Muscle Fibers Muscle satellite cell Muscular Dystrophies Mutation Myoblasts Natural regeneration Patients Property Proteins Protocols documentation Quality of life Reporting Research Sarcolemma Skeletal Muscle Somatic Cell Source Stem cell transplant Structure Teratoma Testing Therapeutic Tissues Transduction Gene Transplantation c-Myc Staining Method cell type embryonic stem cell gene therapy improved induced pluripotent stem cell mdx mouse muscle degeneration novel novel therapeutic intervention practical application prevent programs receptor receptor expression repaired restoration satellite cell self-renewal transcription factor

项目摘要

DESCRIPTION (provided by applicant): Duchenne Muscular Dystrophy (DMD) is caused by mutations in the gene coding for dystrophin, which functions to maintain muscle fiber structure and function, preventing it from being damaged by muscle contraction. Presently, there is no definitive treatment for DMD patients. Current therapies focus on prolonging survival and improving quality of life. Definitive treatment will require that functional dystrophin protein is restored in all affected muscle groups. Possible approaches include cell therapy, gene therapy or a combination of the two. We hope that transplantation of a particular type of muscle repair cell will help us to develop new therapeutic approaches to this disease. Muscle stem cells, termed satellite cells, isolated from healthy donors or patients should be able to provide dystrophin and repair muscle damage in DMD patients. For efficient therapy of DMD, satellite cells which maintain the self-renewing ability are necessary. Therefore, in this proposal, (1) we will focus on the study of how cultured satellite cells maintain their self-renewal capacity. In addition, systemic injection of satellite cells is an essential protocol that will provide healthy ells into all affected muscle tissues in DMD patients. Thus, (2) we will attempt to improve systemic delivery methods for satellite cells using a novel homing receptor expression. Furthermore, we need to use cells that are not rejected by a patient's immune system. (3) We are able to generate an unlimited number of satellite cells from induced pluripotent stem cells (iPSCs) derived from the patient's myoblasts. In combination with gene transduction, this concerted approach will help us to make satellite cells that can be transplanted into patients for a definitie cure of DMD.

描述（由申请人提供）：Duchenne肌肉营养不良症（DMD）是由编码肌营养不良蛋白的基因中的突变引起的，该突变的功能可维持肌肉纤维的结构和功能，从而阻止了肌肉的肌肉收缩受损。目前，对于DMD患者没有明确的治疗方法。当前的疗法集中于延长生存和改善生活质量。确定的治疗将要求在所有受影响的肌肉组中恢复功能性肌营养不良蛋白。可能的方法包括细胞疗法，基因疗法或两者的组合。我们希望移植特定类型的肌肉修复细胞将有助于我们开发新的治疗方法。从健康供体或患者中分离出的卫星细胞的肌肉干细胞应能够在DMD患者中提供肌营养不良蛋白并修复肌肉损伤。为了进行有效的DMD治疗，需要保持自我更新能力的卫星细胞。因此，在此提案中，（1）我们将重点研究培养的卫星细胞如何保持其自我更新能力的研究。此外，全身注射卫星细胞是必不可少的方案，它将为DMD患者的所有受影响的肌肉组织提供健康的ELL。因此，（2）我们将尝试使用新型的归巢受体表达来改善卫星细胞的全身传递方法。此外，我们需要使用不被患者免疫系统拒绝的细胞。（3）我们能够从源自患者的肌细胞的诱导多能干细胞（IPSC）中生成无限数量的卫星细胞。结合基因转导，这种一致的方法将有助于我们制造可以将其移植到患者中以确定DMD的卫星细胞。