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

Paola Frölichsthal-Schoeller, Angelo L. Vescovi, Craig A. Krekoski, Gillian Murphy, Dylan R. Edwards, Peter Forsyth

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37 Citations (Scopus)


The expression and regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in neuroectodermal precursor cells is undocumented. We report the presence of MMP-2, but no MMP-9, and of all the four known TIMPs in neuroepithelial stem cells isolated from the human CNS. The expression of TIMP-1, TIMP-2 and TIMP-3 was unchanged following stem cells differentiation into neurons and glia. In contrast, while MMP-2 and TIMP-4 were 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-conditioned media, reflecting a 6-fold decrease in mRNA expression. Interestingly, TIMP-4 also differed from the other TIMPs in that it was cell- associated in the stem cells, where this fraction remained unchanged upon differentiation. Hence, regulation of selective MMPs and TIMPs occurs during differentiation of human neural precursors suggesting that MMP-2 and TIMP-4 in particular may perform regulatory roles in the developing CNS.
Original languageEnglish
Pages (from-to)345-351
Number of pages7
Issue number2
Publication statusPublished - 5 Feb 1999


  • Human CNS stem cells
  • Matrix metalloproteinases
  • Neural development
  • Neural precursors
  • Tissue inhibitors of metalloproteinases

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