Human cranial bone-derived mesenchymal stem cells cultured under simulated microgravity can improve cerebral infarction in rats

Kuwabara Masashi

Mitsuhara Takafumi

Teranishi Masataka

Okazaki Takahito

Takeda Masaaki

Ishii Daizo

Kondo Hiroshi

Shimizu Kiyoharu

Hosogai Masahiro

Hara Takeshi

Maeda Yuyo

Kurose Tomoyuki

Kawahara Yumi

Yuge Louis

Horie Nobutaka

Experimental Neurology

The efficacy of transplanting human cranial bone-derived mesenchymal stem cells (hcMSCs) cultured under simulated microgravity (sMG) conditions has been previously reported; however, their effect on cerebral infarction remains unknown. Here, we examined the efficacy of transplanting hcMSCs cultured in an sMG environment into rat models of cerebral infarction. For evaluating neurological function, hcMSCs cultured in either a normal gravity (1G) or an sMG environment were transplanted in rats 1 day after inducing cerebral infarction. The expression of endogenous neurotrophic, axonal, neuronal, synaptogenic, angiogenic, and apoptosis-related factors in infarcted rat brain tissue was examined using real-time polymerase chain reaction and western blotting 35 days after stroke induction. The RNAs of hcMSCs cultured under 1G or sMG environments were sequenced. The results showed that neurological function was significantly improved after transplantation of hcMSCs from the sMG group compared with that from the 1G group. mRNA expressions of nerve growth factor, fibroblast growth factor 2, and synaptophysin were significantly higher in the sMG group than in the 1G group, whereas sortilin 1 expression was significantly lower. RNA sequencing analysis revealed that genes related to cell proliferation, angiogenesis, neurotrophy, neural and synaptic organization, and inhibition of cell differentiation were significantly upregulated in the sMG group. In contrast, genes promoting microtubule and extracellular matrix formation and cell adhesion, signaling, and differentiation were downregulated. These results demonstrate that hcMSCs cultured in the sMG environment may be a useful source of stem cells for the recovery of neurological function after cerebral infarction.

Mesenchymal stem cells

Simulated microgravity

Cerebral infarction

Human cranial bone

eng

Elsevier

© 2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

This is not the published version. Please cite only the published version.

この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。

[DOI] https://doi.org/10.1016/j.expneurol.2024.114947 isVersionOf

日本学術振興会

Japan Society for the Promotion of Science

[Crossref Funder] https://doi.org/10.13039/501100001691

模擬微小重力環境で培養したヒト頭蓋骨由来間葉系幹細胞の脳梗塞ラットへの移植効果

Effects of transplantation of human cranial bone-derived mesenchymal stem cells cultured in a simulated microgravity on rat cerebral infarction model

20K09348