The Use of Pluripotent Stem Cell-Derived Organoids to Study Extracellular Matrix Development during Neural Degeneration
The Use of Pluripotent Stem Cell-Derived Organoids to Study Extracellular Matrix Development during Neural Degeneration
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DOI：
10.3390/cells8030242
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发表时间：
2019-03
期刊：
影响因子：
6
通讯作者：
Yuanwei Yan;Julie Bejoy;Mark Marzano;Yan Li
中科院分区：
文献类型：
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作者：
Yuanwei Yan;Julie Bejoy;Mark Marzano;Yan Li
由于缺乏可靠的人脑研究模型，导致阿尔茨海默病 (AD) 病理（包括淀粉样蛋白斑、神经原纤维缠结和神经元死亡）的机制尚不清楚。基于人类多能干细胞 (hPSC) 的三维类器官系统在模拟神经退行性疾病（包括 AD）方面表现出了巨大的潜力。这些系统与工程工具相结合，可以在体外生成类脑组织，重现复杂的细胞-细胞和细胞-细胞外基质（ECM）相互作用。脑 ECM 在神经分化、增殖、神经元网络和 AD 进展中发挥重要作用。在这篇与脑 ECM 相关的文章中，对基于 hPSC 衍生的神经细胞、组织和脑类器官的 AD 病理学和进展建模的最新进展进行了回顾和总结。此外，还讨论了ECM在hPSC神经分化中的作用以及硫酸乙酰肝素蛋白多糖、硫酸软骨素蛋白多糖和透明质酸对神经变性进展的影响。强调了使用基于干细胞的类器官来研究神经变性和研究 ECM 发育对疾病进展的影响的优势。本文的内容对于理解干细胞微环境中细胞与基质的相互作用以治疗神经退行性变具有重要意义。
The mechanism that causes the Alzheimer’s disease (AD) pathologies, including amyloid plaque, neurofibrillary tangles, and neuron death, is not well understood due to the lack of robust study models for human brain. Three-dimensional organoid systems based on human pluripotent stem cells (hPSCs) have shown a promising potential to model neurodegenerative diseases, including AD. These systems, in combination with engineering tools, allow in vitro generation of brain-like tissues that recapitulate complex cell-cell and cell-extracellular matrix (ECM) interactions. Brain ECMs play important roles in neural differentiation, proliferation, neuronal network, and AD progression. In this contribution related to brain ECMs, recent advances in modeling AD pathology and progression based on hPSC-derived neural cells, tissues, and brain organoids were reviewed and summarized. In addition, the roles of ECMs in neural differentiation of hPSCs and the influences of heparan sulfate proteoglycans, chondroitin sulfate proteoglycans, and hyaluronic acid on the progression of neurodegeneration were discussed. The advantages that use stem cell-based organoids to study neural degeneration and to investigate the effects of ECM development on the disease progression were highlighted. The contents of this article are significant for understanding cell-matrix interactions in stem cell microenvironment for treating neural degeneration.