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Stem Cells for the Treatment of Corneal Fibrosis

Hertsenberg, Andrew J (2015) Stem Cells for the Treatment of Corneal Fibrosis. Doctoral Dissertation, University of Pittsburgh.

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Abstract

The cornea is the optically transparent tissue through which light first enters the eye. Together with the lens, the cornea bends incident light to focus it onto the photosensitive retina. Corneal fibrosis occurs in response to ocular trauma and infection and, by reducing corneal transparency, can impair or completely diminish this function, leading to vision impairment and blindness. Millions of people around the globe suffer from corneal blindness as a result of injury and infection. Fortunately, topical antibiotics and immunosuppressants help to prevent scars from forming. Should a scar develop, corneal transplant is a generally successful procedure that can restore sight to these patients. There are, however, drawbacks and limitations to the procedure in that immunological rejection of the donor graft and a limited supply of donor tissue prevent many patients from sustaining or receiving this treatment. The body of work presented here investigates stem cells as an alternative treatment for vision-impairing fibrotic wounds in the corneal stroma. First, I show that human embryonic stem cells are capable of differentiating to cells with a corneal keratocyte phenotype, a study that may lead to the development of a source of cells to repair damaged corneal tissue. I then show that a population of corneal stromal stem cells can be isolated in a biopsy-like procedure and prevent fibrotic wound healing in the mouse, presenting an autologous source of cells to treat corneal scars. Finally, I investigate a potential mechanism by which these stem cells prevent fibrotic wound healing via immunomodulation and the suppression of neutrophil infiltration to the wound bed. This work moves toward the development of an alternative to corneal transplantation that will bridge the gap between the supply and demand of donor tissue and provide a treatment option with a significantly reduced risk of failure due to rejection.


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Details

Item Type: University of Pittsburgh ETD
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hertsenberg, Andrew Janh77@pitt.eduANH77
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorFunderburgh, James Ljlfunder@pitt.eduJLFUNDER
Committee MemberStolz, Donna Bdstolz@pitt.eduDSTOLZ
Committee MemberHukriede, Neil Ahukriede@pitt.eduHUKRIEDE
Committee MemberSwamynathan, Shivalingappa Ksks47@pitt.eduSKS47
Committee MemberLiu, Hongjunliuh4@pitt.eduLIUH4
Date: 4 May 2015
Date Type: Publication
Defense Date: 23 April 2015
Approval Date: 4 May 2015
Submission Date: 1 May 2015
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 114
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Stem Cells, Cornea, Regeneration, Wound Healing, Fibrosis
Date Deposited: 04 May 2015 11:44
Last Modified: 15 Nov 2016 14:28
URI: http://d-scholarship.pitt.edu/id/eprint/25106

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