Microgravity-induced hepatogenic differentiation of rBMSCs on board the SJ-10 satellite

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) are able to differentiate into functional hepatocytelike cells, which are expected to serve as a potential cell source in regenerative medicine, tissue engineering, and clinical treatment of liver injury. Little is known about whether and how space microgravity is able to direct the hepatogenic differentiation of BMSCs in the actual space microenvironment. In this study, we examined the effects of space microgravity on BMSC hepatogenic differentiation on board the SJ-10 Recoverable Scientific Satellite. Rat BMSCs were cultured and induced in hepatogenic induction medium for 3 and 10 d in custom-made space cell culture hardware. Cell growth was monitored periodically in orbit, and the fixed cells and collected supernatants were retrieved back to the Earth for further analyses. Data indicated that space microgravity improves the differentiating capability of the cells by up-regulating hepatocyte-specific albumin and cytokeratin 18. The resulting cells tended to be maturated, with an in-orbit period of up to 10 d. In space, mechanosensitive molecules of β1-integrin, β-actin, α-tubulin, and Ras homolog gene family member A presented enhanced expression, whereas those of cell-surface glycoprotein CD44, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, vinculin, cell division control protein 42 homolog, and Rho-associated coiled-coil kinase yielded reduced expression. Also observed in space were the depolymerization of actin filaments and the accumulation of microtubules and vimentin through the altered expression and location of focal adhesion complexes, Rho guanosine 5'-triphosphatases, as well as the enhanced exosome-mediated mRNA transfer. This work furthers the understanding of the underlying mechanisms of space microgravity in directing hepatogenic differentiation of BMSCs.-Lü, D., Sun, S., Zhang, F., Luo, C., Zheng, L., Wu, Y., Li, N., Zhang, C., Wang, C., Chen, Q., Long, M. Microgravity-induced hepatogenic differentiation of rBMSCs on board the SJ-10 satellite.

Keywords: hepatocyte; mechanotransduction; mesenchymal stem cells; signaling pathway.