Marotta Davide, Ijaz Laraib, Barbar Lilianne, Nijsure Madhura, Stein Jason, Pirjanian Nicolette, Kruglikov Ilya, Clements Twyman, Stoudemire Jana, Grisanti Paula, Noggle Scott A, Loring Jeanne F, Fossati Valentina
The New York Stem Cell Foundation Research Institute, New York, NY 10019, United States.
Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, United States.
Stem Cells Transl Med. 2024 Dec 16;13(12):1186-1197. doi: 10.1093/stcltm/szae070.
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.
在近地轨道（LEO）的国际空间站（ISS）上进行的研究表明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。我们从患有原发性进行性多发性硬化症（PPMS）或帕金森病（PD）的个体以及无症状对照者的诱导多能干细胞（iPSC）中分别向皮质和多巴胺能命运分化，生成三维人类神经类器官，并将它们与同基因小胶质细胞结合。这些类器官在国际空间站（ISS）上使用一种新型密封冻存管培养方法培养了一个月，同时在地球上设置了一组平行样本。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促进神经突生长。我们的结果表明，在低地球轨道培养的皮质类器官和多巴胺能类器官中，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，这表明细胞在低地球轨道成熟得更快。这项研究将通过更多任务继续进行，以了解加速成熟的潜在机制，并研究其他神经系统疾病。我们的目标是利用在低地球轨道研究神经细胞的机会，更好地理解和治疗地球上的神经退行性疾病，并帮助减轻太空旅行可能产生的不良神经影响。
