Transplantation of EGF-responsive neurospheres from GFP transgenic mice into the eyes of rd mice.
The isolation of stem cells from various regions of the central nervous system has raised the possibility of using them as a donor cell source for cell transplantation, where they offer great promise for repair of the diseased brain, spinal cord, and retina. Here, we have studied the migration, integration, and differentiation of EGF-responsive neurospheres isolated from the brains of green fluorescent protein transgenic mice and transplanted into the eyes of mature rd mice, a model of retinitis pigmentosa. While grafts of freshly isolated postnatal day 8 retina expressed many markers characteristic of mature retina (e.g. rhodopsin, protein kinase C), very few of the grafted cells migrated into host retina. EGF-responsive neurospheres, conversely, readily migrated into and integrated with the remaining host retina, but showed a very limited ability to differentiate into mature retinal neurons. While the progenitor cells used here show remarkable ability to integrate with host retina and develop some attributes of retinal cells, the failure to fully differentiate into retinal cells suggests that they already express some level of terminal commitment that precludes using them to replace lost photoreceptors.
Lu
B
B
Moran Eye Center, 75 N. Medical Drive, University of Utah Health Science Center, Salt Lake City, UT 84132, USA.
Kwan
T
T
Kurimoto
Y
Y
Shatos
M
M
Lund
R D
RD
Young
M J
MJ
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D016380:Brain Tissue Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D012160:Retina / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor