Dong Hyon Kim, Ju-Yeon Kim, Ji Hyun Kim, Dahm Lee, Wonil Oh and Jong Wook Chang
Accepted Abstracts: J Cell Sci Ther
Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB- MSCs) with BV2 microglia under amyloid β 42(A β 42) exposure induced a reduction of A β 42 in the medium as well as an overexpression of the A β -degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under A β 42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added A β 42 in the co- cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer?s disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, A β 42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward A β deposits. Th ese data suggest that hUCB- MSCs-derived sICAM-1 decreases A β plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway
