ROLES OF ACTIVATED ASTROCYTES IN BONE MARROW STROMAL CELL PROLIFERATION AND DIFFERENTIATION

Local microenvironment plays an important role in determining the fate choice of stem cells in the central nervous system (CNS). Astrocytes, a major component of local microenvironment in the CNS, have been demonstrated to influence the proliferation and neural differentiation of stem cells including neural stem/progenitor cells, embryonic stem cells and bone marrow stromal cells (BMSCs). However, it has remained to be ascertained if inflammation-activated astrocytes can affect the behavior of BMSCs. To this end, astrocyte-conditioned medium (ACM) was prepared in this study for treatment of BMSCs. The ACM derived from Wistar rat astrocytes stimulated by lipopolysaccharide for 12, 36 or 72 h, respectively, served as inflammatory ACM (12 h ACM, 36 h ACM and 72 h ACM), while that from unstimulated astrocytes was used as normal control astrocyte-conditioned medium (N-ACM). The results showed that the proliferation and neural differentiation of BMSCs grown in inflammatory ACM were significantly increased compared with those grown in N-ACM. The efficiency of BMSCs exposed to 36 h ACM was significantly greater than that of those exposed to 12 or 72 h ACM. Following neutralization of interleukin-6 (IL-6) of the ACM, both the proliferation and astrocytic differentiation of BMSCs were decreased; on the other hand, the neuronal differentiation was significantly increased. The present findings suggest that inflammation-activated astrocytes can facilitate the proliferation and neural differentiation of BMSCs and activated astrocytes at different phase after CNS injuries might have distinct effects on BMSCs. Moreover, astrocyte-derived IL-6 participates in the proliferation and neural differentiation of BMSCs. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.