Tissue-Specific Stem Cells

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Stem Cell Therapy Restores Transparency to Defective Murine Corneas†‡

  1. Yiqin Du1,
  2. Eric C. Carlson2,
  3. Martha L. Funderburgh1,
  4. David E. Birk3,
  5. Eric Pearlman2,
  6. Naxin Guo4,
  7. Winston W.-Y. Kao5,
  8. James L. Funderburgh1,§,*

Article first published online: 9 APR 2009

DOI: 10.1002/stem.91

Issue

STEM CELLS

STEM CELLS

Volume 27, Issue 7, pages 1635–1642, July 2009

Additional Information

How to Cite

Du, Y., Carlson, E. C., Funderburgh, M. L., Birk, D. E., Pearlman, E., Guo, N., Kao, W. W.-Y. and Funderburgh, J. L. (2009), Stem Cell Therapy Restores Transparency to Defective Murine Corneas. STEM CELLS, 27: 1635–1642. doi: 10.1002/stem.91

Author Information

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  1. §

    Telephone: 412–647–3853; Fax: 412–647–5880

*Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

  1. †

    Author contributions: Y.D.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; E.C.C.: conception and design, provision of study material, collection and assembly of data, data analysis and interpretation, final approval of manuscript; M.L.F.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; D.E.B.: conception and design, financial support, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; E.P.: provision of study material, financial support, administrative support, manuscript writing, final approval of manuscript; Winston W-Y Kao: provision of study material, manuscript writing, final approval of manuscript; J.L.F.: conception and design, financial support, administrative support, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; N.G.: collection and assembly of data, final approval of manuscript.

  2. ‡

    First published online in STEM CELLS EXPRESS April 9, 2009.

  3. §

    Telephone: 412–647–3853; Fax: 412–647–5880

Publication History

  1. Issue published online: 6 JUL 2009
  2. Article first published online: 9 APR 2009
  3. Accepted manuscript online: 9 APR 2009 12:00AM EST
  4. Manuscript Accepted: 25 MAR 2009
  5. Manuscript Received: 11 DEC 2008

Funded by

  • National Institutes of Health. Grant Numbers: EY016415, EY09368, EY10320, EY11373, EY005129, EY11845, P30-EY08098
  • Research to Prevent Blindness and the Eye and Ear Foundation of Pittsburgh

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Keywords:

  • Side Population;
  • Cornea;
  • Scarring;
  • Cellular therapy;
  • Tissue regeneration;
  • Tissue-specific stem cells;
  • Xenogeneic stem cell transplantation;
  • Mouse

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. STEM CELLS 2009;27:1635–1642

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