02443nas a2200289   4500000000100000008004100001260001500042100001900057700001600076700002000092700002000112700001600132700002400148700001900172700002000191700002000211700001900231700001900250700002000269700002200289245010200311856004300413300001400456490000700470520166200477022001402139       2024                            d  c2024-12-011 aDavide Marotta1 aLaraib Ijaz1 aLilianne Barbar1 aMadhura Nijsure1 aJason Stein1 aNicolette Pirjanian1 aIlya Kruglikov1 aTwyman Clements1 aJana Stoudemire1 aPaula Grisanti1 aScott A Noggle1 aJeanne F Loring1 aValentina Fossati00aEffects of microgravity on human iPSC-derived neural organoids on the International Space Station  uhttps://doi.org/10.1093/stcltm/szae070  a1186-11970 v133 aResearch 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.  a2157-6564