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时间和细胞特异性的BMP信号激活抑制了冠状细胞缩
Stephen J Gadomski1,2,3, Byron W H Mui1,3,4,5, Raphael Gorodetsky6
1Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
iScience
|August 28, 2024
概括
人类骨髓 stromal 细胞 (hBMSCs) 在覆盖氨酸的纤维素微粒 (HyA-FMBs) 上形成软骨. 这项研究阐明了该机制,表明工程化球体在体内产生稳定,非缩性软骨.
科学领域:
- 再生医学是一种再生医学.
- 干细胞生物学 干细胞生物学
- 软骨组织工程 软骨组织工程
背景情况:
- 目前用于退行性软骨疾病的干细胞疗法受到质软骨形成和维护的缺乏理解的阻碍.
- 人类骨髓层细胞/骨干干细胞 (hBMSCs/SSCs) 可以在酸涂层纤维素微珠 (HyA-FMBs) 上培养时产生稳定的质软骨,但根本机制尚未完全理解.
研究的目的:
- 阐明HBMSCs/SSCs在HyA-FMBs上形成稳定的质软骨的机制.
- 为了研究骨形态蛋白 (BMP) 信号在体生成中的作用,使用工程人类诱导的多能干细胞 (hiPSC) 衍生的硬质瘤细胞.
主要方法:
- 培养的hBMSC/SSC/HyA-FMB有机体用于分析BMP信号动态在体差异化过程中.
- 已建立的hiPSC衍生性硬化瘤细胞,并用转化生长因子β (TGF-β) 单独或与BMP2和生长分化因子5 (GDF5) 结合治疗它们.
- 在试验室中评估了状球体形成和基因表达标记物 (COL2A1,ACAN,PRG4,COL10A1,ALP),并在免疫受损的动物中移植后评估了软骨形成.
主要成果:
- 在hBMSC/SSC/HyA-FMB有机体中,在分化早期,BMP信号传递暂时减少,随后在体IGFBP5+/MGP+细胞中恢复.
- 在TGF-β/BMP2/GDF5治疗由hiPSC衍生的硬质瘤细胞中,诱导了SOX9+色球体,具有关键软骨基因基因 (COL2A1,ACAN,PRG4) 的高表达和高缩标志物 (COL10A1,ALP) 的低表达.
- 在体内移植的桃体衍生细胞/HyA-FMBs导致形成持久的,非缩性软骨,与移植的hBMSCs/SSCs/HyA-FMBs不同.
结论:
- 这项研究澄清了BMP信号通路,该通路对于使用hBMSCs/SSCs在HyA-FMBs上形成状软骨至关重要.
- 从hiPSC硬质瘤细胞中获得的工程性球体有效地在体内产生稳定,非缩的软骨,为软骨修复提供了有前途的细胞来源.
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