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

Neuroreport. 1999 Feb 5;10(2):345-51. doi: 10.1097/00001756-199902050-00025.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Collagenases / genetics
  • Collagenases / metabolism
  • Diencephalon / embryology*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Gelatinases / genetics
  • Gelatinases / metabolism*
  • Humans
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • RNA, Messenger / metabolism
  • Stem Cells / metabolism*
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism*


  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9