Developing stem cell therapy as an alternative to corneal transplants.
Research details
- Type of funding: PhD Studentship
- Grant Holder: Prof Julie Daniels
- Institute: UCL Institute of Ophthalmology
- Region: London
- Start date: October 2014
- End Date: September 2017
- Priority: Treatment
- Eye Category: Corneal & external
Overview
It is vital that the front surface of the eye (the cornea) stays clear, so that light can reach the light-sensitive layer at the back of the eye (the retina). But around 10 million people worldwide are blind due to damaged corneas – usually from scarring caused by injury or infection.
In many cases, people can get their sight back by having transplant surgery to replace the cornea with a healthy one from a donor. But there aren’t enough donors to treat everyone who might benefit, so we need to find an alternative.
Stem cell transplants have successfully restored vision to patients who have had problems with the outer layer of the cornea. But – until now – the best treatment for people with deeper scarring has still been to transplant the whole cornea.
The eye has its own supply of stem cells that help the cornea stay clear. Some look after the surface and others repair wear and tear deeper in the cornea. So in this project the researchers are
- finding the best place in the cornea to supply the right sort of stem cell
- learning how to grow larger numbers of these cells in a lab dish without changing how they work; and then
- seeing if it’s possible to engineer them to treat different types of scarring
Stem cell therapy could help restore vision to people with scarred corneas from injury or infection. It could also benefit people with an inherited condition that means their eyes don’t contain the stem cells that repair natural wear and tear in the cornea. It may also help people with keratoconus, an inherited condition that causes sight loss by changing the shape of the cornea.
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Scientific summary
Development of therapeutic applications for corneal stromal stem cells
This project addresses the challenge of scarring of the cornea, which blinds 10 million people worldwide. Therapeutic corneal transplantation is limited by the global shortage of suitable donor tissue and high risk of tissue rejection and is not applicable to all disorders.
Stem cell therapy has the potential to address this significant unmet clinical need. Availability of large banks of allogeneic stem cells (that the recipient does not reject) for direct use as a therapy or for tissue engineering would be ideal, however, autologous solutions may be feasible in the short term.
Mesenchymal stem cells (MSC) are especially promising due to their reported immune-modulatory capacity to delay the host rejection of allogeneic tissue in human recipients. A population of MSC-like cells, called Corneal Stromal Stem Cells (CSSC), reside in the corneal limbus and can be made to differentiate into keratocytes (which maintain healthy transparent corneal stroma). Promisingly, human CSSC were not rejected when transplanted into murine corneas and were able to reduce haze.
The team is using their tissue engineering expertise to develop methods for delivery of CSSC to patients. Specifically they are comparing novel collagen-based, GMP compliant ‘RAFT’ technology and a rapidly degradable fibrin-based hydrogel. They propose that CSSC will bring benefit to patients with limbal epithelial stem cell deficiency induced haze and those with corneal scarring from other causes by providing a tissue equivalent (TE) incorporating CSSC or keratocytes depending upon clinical need.
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Meet the team
