实验室培养的自我可持续肌肉细胞修复肌肉损伤和疾病,小鼠研究显示
04/20/2022
![Image of mouse muscle](/-/media/images/newsreleases/2022/04/newsroom-vanessa-mouse-muscle-april-20.jpeg?h=720&iar=0&w=1280&hash=39C08E0742381EAD21CD7F0CE6F4946D)
In proof-of-concept experiments, 约翰霍普金斯大学的医学科学家表示,他们已经成功培养出能够自我更新并修复老鼠肌肉组织损伤的人类肌肉干细胞, 有可能推进人类治疗肌肉损伤和肌肉萎缩疾病的努力.
A report on the experiments was published April 7 in Cell Stem Cell.
To make the self-renewing stem cells, 科学家们从实验室培养的人类皮肤细胞开始,这些细胞经过基因重组,进入了一种更原始的状态,在这种状态下,这些细胞几乎有可能变成体内任何类型的细胞. At this point, the cells are known as induced pluripotent stem (IPS) cells, 将它们与标准细胞生长因子和营养物质混合,促使它们分化成特定的细胞类型.
In the laboratory, 长期以来,科学家们一直能够将IPS细胞转化为各种类型的细胞, including skin and brain cells. What has been far more difficult, say the researchers, 是将IPS细胞转化为特定器官的自我更新干细胞的能力吗.
The research team, led by Gabsang Lee, Ph.D., D.V.M., professor of neurology and member of the Institute for Cell Engineering at Johns Hopkins Medicine, 用营养丰富的肉汤诱导诱导多能干细胞转化为肌肉干细胞. Further studies are planned, Lee says, 进一步检查配方以确定哪些成分可能是酿造肌肉干细胞的关键.
Lee is co-founder of Vita Therapeutics Inc., a Baltimore, Maryland-based cell engineering company, 他们希望将肌肉干细胞疗法推向市场,治疗肌肉萎缩症, including muscular dystrophy. 他警告说,这种干细胞疗法目前还不可行.
In proof-of-concept experiments with mice, 研究小组试图确定新发育的细胞将在活体动物中迁移到哪里, and if they could repair damaged tissue.
研究小组报告说,当他们将肌肉干细胞注射到老鼠肌肉中时, the cells moved to an area of the muscles known as the niche, where other natural muscle stem cells are typically found, and stayed there for more than four months.
研究小组随后使用两种不同的方法来确定肌肉干细胞是否能修复受损组织.
In one method, 研究人员将肌肉干细胞移植到经过基因工程改造的小鼠体内,并在没有免疫系统的情况下进行繁殖,以避免移植细胞的排斥反应. 然后,他们将老鼠暴露在一种肌肉降解毒素和辐射中,以消除老鼠体内已经存在的肌肉干细胞.
在肌肉组织的毒素和辐射损伤部位, 研究人员发现,移植的人类肌肉干细胞发育成成肌细胞, 一种肌肉结构细胞,通过融合和发展正常肌肉特征的微纤维来修复损伤. 他们还发现,一些移植的人类肌肉干细胞迁移到生态位,并表现得像老鼠体内自然发现的肌肉干细胞一样.
In a second set of experiments, 研究人员将肌肉干细胞移植到含有抗肌萎缩蛋白基因突变的基因工程小鼠体内, which results in Duchenne muscular dystrophy, a muscle wasting disorder in mice and humans.
研究人员发现,移植的肌肉干细胞可以移动到肌肉生态位区域. Over several months, 试验表明,移植后的小鼠在小型跑步机上的跑步距离是未移植小鼠的两倍, a measure of muscle strength.
“这些肌肉干细胞可能被开发成多种肌肉疾病的治疗方法,” says Lee.
研究小组计划在其他肌肉相关疾病的小鼠模型中研究这些细胞在运动医学中的潜在用途, trauma, and age-related muscle loss.
本研究由美国国立卫生研究院(R01NS093213)提供支持, R01-AR076390, K01-AR074048, R01AR070751), the Maryland Stem Cell Research Fund, the Maryland Stem Cell Fellowship, Vita Therapeutics, the Muscular Dystrophy Association, the Peter and Carmen Lucia Buck Foundation, the American Heart Association Predoctoral Fellowship, an American Heart Association Career Development Award, an American Heart Association Established Investigator Award, and National Research Foundation of Korea grants.
根据Vita Therapeutics和约翰霍普金斯大学的许可协议,Lee, Kathryn R. Wagner, 和大学有权获得与本新闻稿中讨论的研究中所述技术相关的版税分配. Vita Therapeutics provided partial support for this study. 李、瓦格纳和彼得·安德森是Vita Therapeutics的联合创始人,并持有该公司的股权.
其他参与这项研究的科学家包括孙丛山, Suraj Kannan, In Young Choi, HoTae Lim, Hao Zhang, Grace Chen, Nancy Zhang, Seong-Hyun Park, Carlo Serra, Shama Iyer, Thomas Lloyd, Chulan Kwon and Peter Andersen of Johns Hopkins; Richard Lovering of the University of Maryland School of Medicine (now at the National Institutes of Health); Su Bin Lim of the Ajou University School of Medicine in South Korea; and Congshan Sun and Kathryn Wagner, 他曾在约翰霍普金斯大学和肯尼迪克里格研究所工作,现在在Vita Therapeutics和F. Hoffman La-Roche Inc., respectively.