Stem Cell Therapy Restores Transparency to Defective Murine Corneas

Author:

Du Yiqin1,Carlson Eric C.2,Funderburgh Martha L.1,Birk David E.3,Pearlman Eric2,Guo Naxin4,Kao Winston W.-Y.5,Funderburgh James L.1

Affiliation:

1. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

2. Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA

3. Department of Pathology & Cell Biology, University of South Florida, Tampa, Florida, USA

4. Department of Ophthalmology, University of Rochester Eye Institute, Rochester, New York, USA

5. Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA

Abstract

Abstract 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. Disclosure of potential conflicts of interest is found at the end of this article.

Funder

National Institutes of Health

Research to Prevent Blindness and the Eye and Ear Foundation of Pittsburgh

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

Reference22 articles.

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2. Keratocyte and fibroblast phenotypes in the repairing cornea;Fini;Prog Retin Eye Res,1999

3. Corneal blindness: A global perspective;Whitcher;Bull World Health Organ,2001

4. Altered KSPG expression by keratocytes following corneal injury;Carlson;Mol Vis,2003

5. Keratan sulfate: Structure, biosynthesis, and function;Funderburgh;Glycobiology,2000

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