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CNS progenitor cells promote a permissive environment for neurite outgrowth via a matrix metalloproteinase-2-dependent mechanism

Zhang, Yiqin; Klassen, Henry J.; Tucker, Budd A.; Perez, Maria Thereza LU and Young, Michael J. (2007) In Journal of Neuroscience 27(17). p.4499-4506
Abstract
Transplantation of progenitor cells to the CNS has shown promise in neuronal and glial replacement and as a means of rescuing host neurons from apoptosis. Here we examined the effect of progenitor grafts on neurite extension in the degenerating retina of rd1 ( retinal degeneration 1) mice. Transplantation of retinal progenitor cells induced increased matrix metalloproteinase-2( MMP2) secretion, partly from activated glial cells, which was then activated by neuronally expressed MMP14. Active MMP2 resulted in proteolysis of the neurite outgrowth inhibitors CD44 and neurocan in the degenerative retina, allowing significantly increased neurite outgrowth across the border between abutting nondystrophic and rd1 retinas. Progenitor-induced... (More)
Transplantation of progenitor cells to the CNS has shown promise in neuronal and glial replacement and as a means of rescuing host neurons from apoptosis. Here we examined the effect of progenitor grafts on neurite extension in the degenerating retina of rd1 ( retinal degeneration 1) mice. Transplantation of retinal progenitor cells induced increased matrix metalloproteinase-2( MMP2) secretion, partly from activated glial cells, which was then activated by neuronally expressed MMP14. Active MMP2 resulted in proteolysis of the neurite outgrowth inhibitors CD44 and neurocan in the degenerative retina, allowing significantly increased neurite outgrowth across the border between abutting nondystrophic and rd1 retinas. Progenitor-induced enhancement of outgrowth was abrogated by an MMP inhibitor or by coculture with retinal explants from MMP2(-/-) mice. This study provides the first identification of an MMP2-dependent mechanism by which exogenous progenitor cells alter the host environment to promote neural regeneration. This suggests a novel therapeutic role for progenitor cells in the treatment of CNS degenerative diseases. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neurite, cell migration, cell transplantation, retina, progenitor cell, outgrowth, MMP-2
in
Journal of Neuroscience
volume
27
issue
17
pages
4499 - 4506
publisher
Society for Neuroscience
external identifiers
  • wos:000246293900003
  • scopus:34247494789
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0200-07.2007
language
English
LU publication?
yes
id
03cf79c1-e6af-4f63-8438-4c4c9e4ef96d (old id 662568)
date added to LUP
2007-12-19 11:05:49
date last changed
2017-10-31 15:20:38
@article{03cf79c1-e6af-4f63-8438-4c4c9e4ef96d,
  abstract     = {Transplantation of progenitor cells to the CNS has shown promise in neuronal and glial replacement and as a means of rescuing host neurons from apoptosis. Here we examined the effect of progenitor grafts on neurite extension in the degenerating retina of rd1 ( retinal degeneration 1) mice. Transplantation of retinal progenitor cells induced increased matrix metalloproteinase-2( MMP2) secretion, partly from activated glial cells, which was then activated by neuronally expressed MMP14. Active MMP2 resulted in proteolysis of the neurite outgrowth inhibitors CD44 and neurocan in the degenerative retina, allowing significantly increased neurite outgrowth across the border between abutting nondystrophic and rd1 retinas. Progenitor-induced enhancement of outgrowth was abrogated by an MMP inhibitor or by coculture with retinal explants from MMP2(-/-) mice. This study provides the first identification of an MMP2-dependent mechanism by which exogenous progenitor cells alter the host environment to promote neural regeneration. This suggests a novel therapeutic role for progenitor cells in the treatment of CNS degenerative diseases.},
  author       = {Zhang, Yiqin and Klassen, Henry J. and Tucker, Budd A. and Perez, Maria Thereza and Young, Michael J.},
  issn         = {1529-2401},
  keyword      = {neurite,cell migration,cell transplantation,retina,progenitor cell,outgrowth,MMP-2},
  language     = {eng},
  number       = {17},
  pages        = {4499--4506},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {CNS progenitor cells promote a permissive environment for neurite outgrowth via a matrix metalloproteinase-2-dependent mechanism},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.0200-07.2007},
  volume       = {27},
  year         = {2007},
}