Muscle regeneration through stem cell transplantation

通过干细胞移植实现肌肉再生

• 批准号: 6577407
• 负责人: JOHNNY HUARD
• 金额: $ 24.2万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6577407
• 关键词: CD34 molecule; SCID mouse; cell adhesion; cell proliferation; cytotoxic T lymphocyte; dystrophin; enzyme linked immunosorbent assay; flow cytometry; fluorescent in situ hybridization; helper T lymphocyte; immunocytochemistry; regeneration; stem cell transplantation; striated muscles; tissue /cell culture; transplantation immunology; vascular endothelial growth factors

DESCRIPTION (provided by applicant): We recently have used a modified preplate technique to isolate 3 populations of myogenic cells from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although 2 of these populations display satellite cell characteristics, the third population consists of long_term proliferating (LTP) cells expressing hematopoietic stem cell markers. The stem cell characteristics of the LTP cells include the abilities to retain their phenotype for more than 30 passages in culture (self-renewal) and to differentiate into various lineages, including muscle, neural, osteogenic, and endothelial. The transplantation of the LTP cells, in contrast to satellite cell transplantation, significantly improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The overall goal of our proposed project is to further investigate important features of the LTP cells (i.e., sources and mechanisms involved with the improved transplantation capacity) that are paramount to their potential use in transplantation to improve muscle regeneration and deliver dystrophin to dystrophic muscle. In this project we will investigate potential sources of the LTP cells by determining their relationship to satellite cells and to the Side Population (SP) stem cells derived from skeletal muscle (Aim #1). We subsequently will investigate mechanisms by which the LTP cells display an improved transplantation capacity in skeletal muscle. We will evaluate the relative effects of the proliferation and differentiation kinetics of the cells (Aim #2) and determine the possibility that immune_privileged cell behavior also plays a role in the increased regenerative capacity of LTP cells in skeletal muscle (Aim #3). Analysis of the relative importance of the LTP cells' self-renewal and multipotent capabilities will shed light on the contribution of stem cell characteristics to the improved transplantation capacity in skeletal muscle (Aim #4). This project might increase our understanding of the basic biology of myogenic cell populations that display stem cell characteristics. This in turn may unveil new techniques to improve muscle regeneration in dystrophic or injured skeletal muscle via the transplantation of muscle-derived stem cells.

描述（由申请人提供）： 我们最近使用了一种改良的预熟练技术，根据其粘附特性和增殖行为将3个肌源性细胞群体与正常小鼠骨骼肌分离。尽管这些人群中有2个显示出卫星细胞特征，但第三个群体由表达造血干细胞标记的长期增殖（LTP）细胞组成。 LTP细胞的干细胞特征包括能够在培养物中保留30多个段落的表型的能力（自我更新），并分化为各种谱系，包括肌肉，神经，成骨和内皮。 与卫星细胞移植相比，LTP细胞的移植显着提高了肌肉再生和肌营养不良蛋白递送到营养不良肌肉的效率。 我们提出的项目的总体目标是进一步研究LTP细胞的重要特征（即与改善的移植能力有关的来源和机制），这对于它们在移植中的潜在使用至关重要，以改善肌肉再生并将肿瘤性肌营养不良蛋白传递到营养不良的肌肉中。在该项目中，我们将通过确定与卫星细胞的关系以及与骨骼肌衍生的侧群（SP）干细胞（AIM＃1）来研究潜在的LTP细胞的潜在来源。随后，我们将研究LTP细胞在骨骼肌中表现出改善的移植能力的机制。我们将评估细胞的增殖和分化动力学的相对影响（AIM＃2），并确定免疫_privileged细胞行为在骨骼肌中LTP细胞的再生能力提高（AIM＃3）中也起作用。 分析LTP细胞自我更新和多能功能的相对重要性将阐明干细胞特征对骨骼肌移植能力提高的贡献（AIM＃4）。 该项目可能会增加我们对显示干细胞特征的肌原细胞群体的基本生物学的理解。 反过来，这可能会推出新技术，以通过移植肌肉衍生的干细胞来改善营养不良或受伤的骨骼肌肌肉的肌肉再生。