Reprogramming and Directed Differentiation of Skeletal Muscle Cells from hPSCs.

hPSC 中骨骼肌细胞的重编程和定向分化。

• 批准号: 8919079
• 负责人: April D Pyle
• 金额: $ 32.07万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8919079
• 关键词: Aging; Antisense Oligonucleotides; Biology; Birth; Cachexia; Cell Differentiation process; Cell Line; Cell Therapy; Cell Transplantation; Cells; Childhood; Clinical Trials; Cues; Cyclic GMP; Development; Disease; Duchenne muscular dystrophy; Dystrophin; Embryo; Embryonic Development; Engraftment; Evaluation; Foundations; Future; Genetic; Genome; Germ Layers; Goals; Grant; Growth; Growth Factor; Human; Human Development; Human body; Immune; In Vitro; Incidence; Knowledge; Laboratories; Lead; Lentivirus Vector; Life; Light; Location; Maintenance; Mediating; Mesoderm; Modeling; Mus; Muscle; Muscle Cells; Muscle Fibers; Muscular Dystrophies; Mutation; Myopathy; PAX7 gene; Paraxial Mesoderm; Pathway interactions; Patients; Pattern; Pluripotent Stem Cells; Population; Progenitor Cell Engraftment; Reading Frames; Recruitment Activity; Regenerative Medicine; Research; Role; SHH gene; Safety; Sampling; Signal Transduction; Skeletal Muscle; Somatic Cell; Source; Specific qualifier value; Stem cells; System; Testing; Therapeutic; Therapeutic Intervention; Time; To specify; Transplantation; Viral; Virus Diseases; Work; cell growth; cell type; design; effective therapy; exon skipping; genetic manipulation; human embryonic stem cell; improved; in vivo; induced pluripotent stem cell; male; mini-dystrophin; molecular recognition; mouse model; myogenesis; nanoparticle; nanostructured; novel; novel strategies; overexpression; pre-clinical; progenitor; public health relevance; regenerative; regenerative therapy; repaired; research clinical testing; research study; satellite cell; screening; self assembly; skeletal; skeletal muscle differentiation; small molecule; stem cell biology; tool; transcription factor; tumorigenic; wasting

DESCRIPTION (provided by applicant): Human pluripotent stem cells (hPSCs) have enormous promise for regenerative medicine as they can differentiate into cells from all three embryonic germ layers. Further hPSCs provide a unique pre-clinical screening tool for evaluating disease mechanisms and therapies in patient samples. Despite the enormous potential of hPSC, many obstacles need to be overcome before the use of stem cells in cell-based therapy will be realized, including an incomplete knowledge of the growth factor cues regulating human skeletal muscle progenitor cell (SMPC) specification, growth and engraftment. In this proposal we will investigate the cellular cues required to direct skeletal muscle fate from hPSCs as seen during embryonic development. We will also develop the first screening approach to identify new regulators of human SMPC fate. It is imperative that we understand how to obtain SMPCs without genetic or viral manipulation. As an alternative approach we have developed a unique non-viral reprogramming platform, which results in superior delivery and reprogramming efficiency, and will be utilized to specify SMPCs without viral or genetic manipulation. We will compare the in vivo engraftment potential of growth factor directed versus reprogrammed SMPCs in a mouse model of DMD. The development of reprogramming strategies to direct SMPC fate and the identification of signals regulating muscle progenitor cell specification and maintenance could improve our basic understanding of human skeletal myogenesis as well as enhance our ability to generate scalable progenitors from humans for muscle disorders including DMD.

描述（由申请人提供）：人类多能干细胞（hPSCs）在再生医学中具有巨大的前景，因为它们可以从所有三个胚胎胚层分化成细胞。此外，hPSCs为评估患者样本中的疾病机制和治疗方法提供了独特的临床前筛选工具。尽管hPSC具有巨大的潜力，但在将干细胞用于基于细胞的治疗之前，还需要克服许多障碍，包括对调节人类骨骼肌祖细胞（SMPC）规格、生长和植入的生长因子线索的不完全了解。在这个建议中，我们将研究指导骨骼肌命运所需的细胞线索