基质弹性调节骨肌肉干细胞在培养中自我更新
P M Gilbert1, K L Havenstrite, K E G Magnusson
1Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|July 22, 2010
概括
模仿肌肉弹性的软基质使成年肌肉干细胞 (MuSCs) 在培养中自我更新. 这一突破支持未来用于肌肉消耗疾病的细胞疗法.
科学领域:
- 生物医学工程 生物医学工程
- 干细胞生物学 干细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 成人干细胞,就像肌肉干细胞 (MuSCs),在体内具有显著的再生潜力.
- 当使用常规方法在体外培养MuSC时,这种再生能力显著下降.
- 细胞微环境,或利基,在干细胞功能和命运中发挥着关键作用.
研究的目的:
- 研究基质生物物理特性对培养中的肌肉干细胞 (MuSC) 命运的影响.
- 开发一种生物工程基质,将关键的利基特征汇总起来,以改善 MuSC 培养.
- 评估在模仿生理肌肉弹性的基板上培养的MuSCs的自我更新和再生潜力.
主要方法:
- 使用生物工程水凝基质,可调节弹性 (12kPa),以模仿本地肌肉组织.
- 采用高度自动化的单细胞跟踪算法来监测MuSC的行为.
- 在小鼠体内移植培养的MuSCs,并使用组织学和生物发光成像技术评估肌肉再生.
主要成果:
- 在柔软的水凝基板 (12kPa) 上培养的MuSCs在体外表现出持续的自我更新.
- 相比之下,在刚性塑料基板上的MuSC (约. 10^6 kPa) 迅速失去它们的再生能力.
- 在软基质上培养的移植的MuSCs在体内肌肉再生中起到了显著的作用.
结论:
- 基质弹性是调节肌肉干细胞 (MuSC) 命运和培养中的自我更新的关键因素.
- 通过生物工程基质来总结生理组织刚性,使成年MuSCs的传播成为可能.
- 这种方法有望开发有效的基于细胞的治疗方法来治疗肌肉消耗的疾病.
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