Stem cell therapy restores transparency to defective murine corneas.
Corneal scarring from trauma and inflammation disrupts vision for millions worldwide, but corneal transplantation, the primary therapy for corneal blindness, is unavailable to many affected individuals. In this study, stem cells isolated from adult human corneal stroma were examined for the ability to correct stromal opacity in a murine model by direct injection of cells into the corneal stroma. In wild-type mice, injected human stem cells remained viable for months without fusing with host cells or eliciting an immune T-cell response. Human corneal-specific extracellular matrix, including the proteoglycans lumican and keratocan, accumulated in the treated corneas. Lumican-null mice have corneal opacity similar to that of scar tissue as a result of disruption of stromal collagen organization. After injection with human stromal stem cells, stromal thickness and collagen fibril defects in these mice were restored to that of normal mice. Corneal transparency in the treated mice was indistinguishable from that of wild-type mice. These results support the immune privilege of adult stem cells and the ability of stem cell therapy to regenerate tissue in a manner analogous to organogenesis and clearly different from that of normal wound healing. The results suggest that cell-based therapy can be an effective approach to treatment of human corneal blindness.
Du
Yiqin
Y
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Carlson
Eric C
EC
Funderburgh
Martha L
ML
Birk
David E
DE
Pearlman
Eric
E
Guo
Naxin
N
Kao
Winston W-Y
WW
Funderburgh
James L
JL
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003316:Corneal Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D007632:Keratan Sulfate / Q000378:metabolism; D000071234:Lumican; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011509:Proteoglycans / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods*
D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D007632:Keratan Sulfate