Expression and modulation of matrix metalloproteinase-2 and tissue inhibitors of metalloproteinases in human embryonic CNS stem cells

THE expression and regulation of matrix metalloproteinases (MMPs) and tissu e inhibitors of MMPs (TIMPs) in neuroectodermal precursor cells is undocume nted. We report the presence of MMP-2, but no MMP-9, and of all the four kn own TIMPs in neuroepithelial stem cells isolated from the human CNS. The ex pression of TIMP-1, TIMP-2 and TIMP-3 was unchanged following stem cells di fferentiation into neurons and glia. In contrast, while MMP-2 and TIMP-4 we re localized to both stem and mature CNS cells, their levels of expression were substantially reduced in the latter. TIMP-4 showed a 23-fold reduction in media conditioned by differentiated cells compared with stem cell-condi tioned media, reflecting a 6-fold decrease in mRNA expression. Interestingl y, TIMP-4 also differed from the other TIMPs in that it was cell-associated in the stem cells, where this fraction remained unchanged upon differentia tion. Hence, regulation of selective MMPs and TIMPs occurs during different iation of human neural precursors suggesting that MMP-2 and TIMP-4 in parti cular may perform regulatory roles in the developing CNS. (C) 1999 Lippinco tt Williams & Wilkins.