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模拟微重力对野生型和马凡氏综合征人诱导多能干细胞来源的类胚体的影响。

Effects of Simulated Microgravity on Wild Type and Marfan hiPSCs-Derived Embryoid Bodies.

作者信息

Spitalieri Paola, Marini Mario, Scioli Maria Giovanna, Murdocca Michela, Longo Giuliana, Orlandi Augusto, Novelli Giuseppe, Sangiuolo Federica

机构信息

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy.

Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

出版信息

Cell Mol Bioeng. 2021 Jun 7;14(6):613-626. doi: 10.1007/s12195-021-00680-1. eCollection 2021 Dec.

Abstract

BACKGROUND

Mechanical unloading in microgravity is thought to induce tissue degeneration by various mechanisms, including the inhibition of regenerative stem cell differentiation. In this work, we investigate the effects of microgravity simulation on early lineage commitment of hiPSCs from healthy and Marfan Syndrome (MFS; OMIM #154700) donors, using the embryoid bodies model of tissue differentiation and evaluating their ultra-structural conformation. MFS model involves an anomalous organization of the extracellular matrix for a deficit of fibrillin-1, an essential protein of connective tissue.

METHODS

models require the use of embryoid bodies derived from hiPSCs. A DRPM was used to simulate microgravity conditions.

RESULTS

Our data suggest an increase of the stemness of those EBs maintained in SMG condition. EBs are still capable of external migration, but are less likely to distinguish, providing a measure of the remaining progenitor or stem cell populations in the earlier stage. The microgravity response appears to vary between WT and Marfan EBs, presumably as a result of a cell structural component deficiency due to fibrillin-1 protein lack. In fact, MFS EBs show a reduced adaptive capacity to the environment of microgravity that prevented them from reacting and making rapid adjustments, while healthy EBs show stem retention, without any structural changes due to microgravity conditions.

CONCLUSION

EBs formation specifically mimics stem cell differentiation into embryonic tissues, this process has also significant similarities with adult stem cell-based tissue regeneration. The use of SMG devices for the maintenance of stem cells on regenerative medicine applications is becoming increasingly more feasible.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12195-021-00680-1.

摘要

背景

微重力环境下的机械卸载被认为会通过多种机制导致组织退化,包括抑制再生干细胞分化。在本研究中,我们利用组织分化的胚状体模型并评估其超微结构构象,研究微重力模拟对来自健康供体和马凡综合征(MFS;OMIM #154700)供体的人诱导多能干细胞早期谱系定向分化的影响。MFS模型涉及细胞外基质的异常组织,原因是原纤维蛋白-1缺乏,原纤维蛋白-1是结缔组织的一种重要蛋白质。

方法

模型需要使用源自人诱导多能干细胞的胚状体。使用旋转壁式生物反应器模拟微重力条件。

结果

我们的数据表明,在模拟微重力条件下培养的胚状体干性增加。胚状体仍能够向外迁移,但分化的可能性较小,这为早期阶段剩余的祖细胞或干细胞群体提供了一种衡量方法。野生型和马凡综合征胚状体的微重力反应似乎有所不同,推测这是由于缺乏原纤维蛋白-1导致细胞结构成分不足所致。事实上,马凡综合征胚状体对微重力环境的适应能力降低,这使得它们无法做出反应并快速调整,而健康胚状体则表现出干细胞保留,且没有因微重力条件而发生任何结构变化。

结论

胚状体的形成特别模拟了干细胞向胚胎组织的分化,这一过程与基于成体干细胞的组织再生也有显著相似之处。在再生医学应用中,使用模拟微重力装置来维持干细胞变得越来越可行。

补充信息

在线版本包含可在10.1007/s12195-021-00680-1获取 的补充材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e45/8630351/bc2eca3a5fe8/12195_2021_680_Fig1_HTML.jpg

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