The simultaneous treatment of MMP-2 stimulants in retinal transplantation enhances grafted cell migration into the host retina

Stem Cells. 2006 Nov;24(11):2406-11. doi: 10.1634/stemcells.2005-0587.


The success of functional retinal cell transplantation has been limited by the low efficiency of the transplanted cell integration into the host retina. Given that the extracellular matrix (ECM) is thought to inhibit entry and axonal outgrowth of grafted neural cells into the host retina, modulation of the ECMs in the host environment may overcome this limitation. Here, we demonstrate that matrix metalloprotease-2 (MMP-2) expression is associated with the high migratory potential of adult rat hippocampus-derived neural stem cells compared with retinal progenitor cells. In addition, MMP-2, as well as its reported inducers concanavalin A and 17beta-estradiol, can trigger the migration of retinal progenitor cells into explanted retinas. Inhibitors of MMP-2 suppressed these effects. Intense cell migration is not required for photoreceptor transplantation; however, the environment that allows the transplanted cells to integrate is most important. Migration of the transplanted cells is a good index of the acceptance of grafted cell of the host tissue. Strategies modulating the environment by MMP-2 stimulation may provide an advance in the development of retinal transplantation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects
  • Adult Stem Cells / enzymology*
  • Adult Stem Cells / transplantation
  • Animals
  • Cell Movement* / drug effects
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Estradiol / pharmacology
  • Hippocampus / cytology
  • Hippocampus / enzymology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 2 / pharmacology
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Mice, Inbred C57BL
  • Neurons / transplantation
  • Organ Culture Techniques
  • Photoreceptor Cells / enzymology
  • Photoreceptor Cells / transplantation*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Retina / cytology
  • Retina / drug effects
  • Retina / enzymology*
  • Stem Cell Transplantation*
  • Transcription, Genetic / drug effects


  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • RNA, Messenger
  • Concanavalin A
  • Estradiol
  • Matrix Metalloproteinase 2