TRANSPLANTATION OF MYOBLASTS

成肌细胞移植

• 批准号: 3410834
• 负责人: ROBERT J WYMAN
• 金额: $ 6.99万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3410834
• 关键词: Drosophilidae; cell age; cell differentiation; early embryonic stage; electron microscopy; electrophysiology; fluorescent dye /probe; gene mutation; genetic disorder; histochemistry /cytochemistry; innervation; larva; metamorphosis; muscle disorders; muscle function; muscle transplantation; myoblasts; neuromuscular function; silver impregnation; temperature sensitive mutant

The experiments which we are proposing will test the ability of muscle stem cells to survive transplantation, to colonize or augment host muscle to reverse the effects of genetically-induced alterations in the integrity and life span of muscle, and to become immortal. Classic experiments by Hadorn and others in Drosophila melanogaste have shown that the epithelial (cuticle- forming) cells associated with the imaginal disks of the presumptive adult appendages can be immortalized by culturing them in the abdomens of adult hosts. This isolates them from the hormonal cues that induce metamorphic cell differentiation. These cultured imaginal disks can then be induced to differentiate normally, months or even years later, by transplanting them into late-larval hosts and allowing them to undergo metamorphosis. The recent development of techniques for marking Drosophila cells with biochemical tags will enable us to determine whether the life span of the adepithelial cells (adult muscle precursors) within the disks can be similarly prolonged by transplantation. The first aim of this project will be to follow the fates of these muscle stem cells as they are transplanted into successive hosts and to determine whether the differentiation of normal adult muscle stem-cell populations can be retarded or accelerated. Our second aim will be to test the ability of the transplanted myoblasts to reverse the effects of genetic mutations which delete a single specific muscle or cause it to degenerate prematurely. We will screen hosts for behavioral and physiological recovery of function, and individually mark and evaluate the activity of their motorneurons. The out come of these experiments should also help to answer our third aim: to determine whether it is defects in the muscles or in the neurons innervating the muscles that are responsible for the muscle deletions.

我们提出的实验将测试的能力 肌肉干细胞在移植中存活、定殖或 增强宿主肌肉以逆转遗传诱导的影响 改变肌肉的完整性和寿命，并成为 不朽。 Hadorn 等人的经典实验 果蝇的研究表明，上皮细胞（角质层） 形成）与成虫盘相关的细胞 假定的成年附肢可以通过培养而永生化 它们在成年宿主的腹部。 这将他们与 诱导变态细胞分化的激素线索。 然后可以诱导这些培养的​​成虫盘分化 通常，几个月甚至几年后，将它们移植到 晚期幼虫宿主并允许它们经历变态。 果蝇标记技术的最新进展 带有生化标签的细胞将使我们能够确定是否 上皮细胞（成人肌肉前体细胞）的寿命 通过移植同样可以延长椎间盘内的时间。 该项目的首要目标是追踪这些人的命运 肌肉干细胞被移植到连续的宿主中 并判断是否分化为正常成人 肌肉干细胞群体可以被延迟或加速。 我们的第二个目标是测试移植者的能力 成肌细胞逆转基因突变的影响 删除单个特定肌肉或导致其退化 过早地。 我们将对房东的行为和行为进行筛查 生理功能恢复情况，并单独标记和 评估他们的运动神经元的活动。 这些实验的结果也应该有助于回答我们的问题 第三个目标：确定是肌肉缺陷还是身体缺陷？ 支配肌肉的神经元负责 肌肉缺失。