人诱导多能干细胞的神经元、星形胶质细胞、少突胶质细胞和小胶质细胞分化形成芯片上的神经组织:一种评估间充质干细胞来源的细胞外囊泡治疗潜力的神经炎症模型。
Differentiation of Neurons, Astrocytes, Oligodendrocytes and Microglia From Human Induced Pluripotent Stem Cells to Form Neural Tissue-On-Chip: A Neuroinflammation Model to Evaluate the Therapeutic Potential of Extracellular Vesicles Derived from Mesenchymal Stem Cells.
发表日期:2023 Nov 08
作者:
Pelin Saglam-Metiner, Elif Duran, Leila Sabour-Takanlou, Cigir Biray-Avci, Ozlem Yesil-Celiktas
来源:
Stem Cell Reviews and Reports
摘要:
干细胞 (SC) 技术的进步使得能够生成能够概括人源化体外三维 (3D) 模型的组织学、分子和生理学特性的细胞模型,以及细胞衍生疗法的生产,例如细胞外囊泡 (EV) 。芯片器官平台和人类诱导多能干细胞 (hiPSC) 衍生的神经/神经胶质细胞的改进为研究 3D 个性化神经组织模型提供了前所未有的系统,并且易于设置和快速输出。在这里,我们重点介绍单源 hiPSC 中神经元、星形胶质细胞、少突胶质细胞和小胶质细胞分化过程中的关键点。此外,我们提出了一个由具有相同遗传背景的分化细胞组成的明确的人源化神经组织芯片模型,以及骨髓间充质干细胞(BMSC)衍生的细胞外囊泡的治疗潜力,以提出一种新的治疗方法用于神经炎症衍生的疾病。约 100 nm CD9 EV 可促进细胞间相互作用的细胞因子对神经组织芯片模型中肿瘤坏死因子-α (TNF-α) 诱导的神经炎症的更强的抗炎和促重塑作用,该模型非常适合模拟真实的神经细胞-胶质病理生理学。© 2023。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下公司)的独家许可。
Advances in stem cell (SC) technology allow the generation of cellular models that recapitulate the histological, molecular and physiological properties of humanized in vitro three dimensional (3D) models, as well as production of cell-derived therapeutics such as extracellular vesicles (EVs). Improvements in organ-on-chip platforms and human induced pluripotent stem cells (hiPSCs) derived neural/glial cells provide unprecedented systems for studying 3D personalized neural tissue modeling with easy setup and fast output. Here, we highlight the key points in differentiation procedures for neurons, astrocytes, oligodendrocytes and microglia from single origin hiPSCs. Additionally, we present a well-defined humanized neural tissue-on-chip model composed of differentiated cells with the same genetic backgrounds, as well as the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles to propose a novel treatment for neuroinflammation derived diseases. Around 100 nm CD9 + EVs promote a more anti-inflammatory and pro-remodeling of cell-cell interaction cytokine responses on tumor necrosis factor-α (TNF-α) induced neuroinflammation in neural tissue-on-chip model which is ideal for modeling authentic neural-glial patho-physiology.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.