April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Prevention of Corneal Scarring by Human Corneal Stromal Stem Cells
Author Affiliations & Notes
  • Andrew Hertsenberg
    Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA
  • Sayan Basu
    Cornea and Anterior Segment Services, L V Prasad Eye Institute, Hyderabad, India
  • James L Funderburgh
    Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA
  • Footnotes
    Commercial Relationships Andrew Hertsenberg, None; Sayan Basu, None; James Funderburgh, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 6043. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Andrew Hertsenberg, Sayan Basu, James L Funderburgh; Prevention of Corneal Scarring by Human Corneal Stromal Stem Cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6043.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: Development of an alternative to keratoplasty could help relieve the world-wide shortage of donated corneal tissue. Our work supports the idea that stem cell therapy may provide such an alternative. Our studies have shown that mesenchymal stem cells from corneal stroma rescue corneal opacity in lumican knockout mice and prevent development of stromal scars in the murine cornea after stromal debridement. The current study was aimed at elucidating the molecular mechanism by which CSSC block corneal scarring.

Methods: Human corneal stromal stem cells (CSSC) were cultured in differentiation conditions in serum-free media on collagen substratum, or with isolated murine immune cells to assess their ability to suppress immune cell activation and/or proliferation. Corneal debridement into the stroma of C57Bl/6 mice was made using an Algerbrush. At the time of wounding, mice either received fibrin gel with embedded human CSSC or fibrin gel alone. Four weeks after wounding, mouse corneas were harvested and sectioned for immunohistochemical detection of CSSC, matrix proteins, immune cells, and human immunomodulatory proteins.

Results: Debrided corneas accumulated stromal deposits of hyaluronan, fibronectin, biglycan, decorin, and collagen type III, components associated with corneal scars. In the presence of CSSC, accumulation of these fibrotic molecules was completely prevented. CSSC also suppressed activation of T-cells by macrophages in an in vitro assay. Immunostaining also revealed that CSSC produce TNF-alpha-stimulated-gene-6-protein (TSG-6) in vivo when applied in fibrin gel at the time of wounding. Additionally, during differentiation in vitro, CSSC markedly upregulated expression of TSG-6.

Conclusions: This study presents the novel observation that TSG6 is expressed by differentiating stem cells in the absence of inflammatory cells. TSG6 is known to reduce corneal inflammation and to suppress TGFb-1 secretion by macrophages. The fibrotic matrix components deposited in the stroma are also known to be expressed in response to TGFb1. Our results therefore suggest that blocking of fibrotic scarring is mediated by TSG6 secreted by CSSC as they differentiate to keratocytes. The mechanism may involve shifting of macrophages from pro-inflammatory (M1) to the regenerative (M2) phenotype resulting in a reduction of TGFb-1.

Keywords: 484 cornea: stroma and keratocytes • 721 stem cells • 765 wound healing  

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.