Effects of microgravity on human iPSC-derived neural organoids on the International Space Station.

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING
Davide Marotta, Laraib Ijaz, Lilianne Barbar, Madhura Nijsure, Jason Stein, Nicolette Pirjanian, Ilya Kruglikov, Twyman Clements, Jana Stoudemire, Paula Grisanti, Scott A Noggle, Jeanne F Loring, Valentina Fossati
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Abstract

Research conducted on the International Space Station (ISS) in low-Earth orbit (LEO) has shown the effects of microgravity on multiple organs. To investigate the effects of microgravity on the central nervous system, we developed a unique organoid strategy for modeling specific regions of the brain that are affected by neurodegenerative diseases. We generated 3-dimensional human neural organoids from induced pluripotent stem cells (iPSCs) derived from individuals affected by primary progressive multiple sclerosis (PPMS) or Parkinson's disease (PD) and non-symptomatic controls, by differentiating them toward cortical and dopaminergic fates, respectively, and combined them with isogenic microglia. The organoids were cultured for a month using a novel sealed cryovial culture method on the International Space Station (ISS) and a parallel set that remained on Earth. Live samples were returned to Earth for analysis by RNA expression and histology and were attached to culture dishes to enable neurite outgrowth. Our results show that both cortical and dopaminergic organoids cultured in LEO had lower levels of genes associated with cell proliferation and higher levels of maturation-associated genes, suggesting that the cells matured more quickly in LEO. This study is continuing with several more missions in order to understand the mechanisms underlying accelerated maturation and to investigate other neurological diseases. Our goal is to make use of the opportunity to study neural cells in LEO to better understand and treat neurodegenerative disease on Earth and to help ameliorate potentially adverse neurological effects of space travel.

微重力对国际空间站上人类 iPSC 衍生神经器官组织的影响。
在低地轨道国际空间站(ISS)上进行的研究显示了微重力对多个器官的影响。为了研究微重力对中枢神经系统的影响,我们开发了一种独特的类器官策略,用于模拟受神经退行性疾病影响的大脑特定区域。我们从诱导多能干细胞(iPSCs)中生成了三维人类神经类器官,这些干细胞来自原发性进行性多发性硬化症(PPMS)或帕金森病(PD)患者以及无症状对照组,分别向皮质和多巴胺能命运分化,并与同源小胶质细胞结合。在国际空间站(ISS)上使用一种新型密封低温培养方法对这些有机体进行了为期一个月的培养,同时还在地球上进行了平行培养。活体样本被送回地球进行 RNA 表达和组织学分析,并附着在培养皿上以实现神经元的生长。我们的研究结果表明,在低地轨道培养的皮质和多巴胺能器官组织中,与细胞增殖相关的基因水平较低,而与成熟相关的基因水平较高,这表明细胞在低地轨道成熟得更快。这项研究还在继续进行多项任务,以了解加速成熟的机制,并研究其他神经系统疾病。我们的目标是利用在低地轨道研究神经细胞的机会,更好地了解和治疗地球上的神经退行性疾病,并帮助改善太空旅行对神经系统的潜在不利影响。
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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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