Stem Cells Dev. 2018 May 23. doi: 10.1089/scd.2017.0299. [Epub ahead of print]

Simulated microgravity culture enhances the neuroprotective effects of human cranial bone-derived mesenchymal stem cells in traumatic brain injury.

Otsuka T¹, Imura T², Nakagawa K³, Shrestha L⁴, Takahashi S⁵, Kawahara Y⁶, Sueda T⁷, Kurisu K⁸, Yuge L⁹.

Abstract

Fundamental cures of central nervous system (CNS) diseases are rarely achieved due to the low regenerative ability of the CNS. Recently, cell-based therapy using mesenchymal stem cells (MSCs) has been explored as effective treatments for CNS diseases. Among the various tissue-derived MSCs, we have isolated human cranial bone-derived MSCs (cMSCs) in our laboratory. In addition, we have focused on simulated microgravity (MG) as a valuable culture environment of MSCs. However, the detailed mechanisms underlying functional recovery from the transplantation of MSCs cultured under MG conditions remain unclear. In this study, we investigated the therapeutic mechanisms of cMSCs transplantation cultured under MG conditions in traumatic brain injury (TBI) model mice. Human cMSCs were cultured under 1G and MG conditions, and cMSCs cultured under MG conditions expressed significantly higher mRNA levels of hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-β). In TBI model mice, the transplantation of cMSCs cultured under MG conditions (group MG) showed greater motor functional improvement compared to the only phosphate buffered saline administration (group PBS). Moreover, the protein expressions of tumor necrosis factor alpha (TNF-α) and the Bax/Bcl-2 ratio were significantly lower at brain injury sites in mice of group MG than those of group PBS. In addition, an in vitro study showed that the conditioned medium of the cMSCs cultured under MG conditions significantly suppressed the cell death of NG108-15 cells exposed to oxidative or inflammatory stress through anti-inflammatory and anti-apoptosis effects. These findings demonstrate that culturing cMSCs under simulated microgravity increases the neuroprotective effects, suggesting that simulated microgravity cultures may be a useful method for cell-based therapy strategies for CNS diseases.