Engineering stem cells to resurface the cornea
Research details
- Type of funding: Project Grant
- Grant Holder: Dr Andrew Hopkinson
- Institute: University of Nottingham
- Region: East Midlands
- Start date: October 2012
- End Date: July 2016
- Priority:
- Eye Category:
Overview
The cornea is the clear front surface of the eye. One million injuries to the cornea are treated every year across Europe.
The 72 hours after injury are crucial. The eye becomes inflamed and can do extreme damage to the tissue. Left untreated, this can lead to blindness. But some patients who need a corneal transplant have to wait months because the eye is still too inflamed to operate.
Dr Hopkinson’s team has been working on a revolutionary new treatment to get the wound to heal before people need surgery. They had already created a sterile biological wound dressing called Omnigen™ that can be placed directly onto the eye quickly and easily within the critical 72 hour window.
So in this study the team are adapting Omingen™ to let stem cells (called corneal stromal cells) to use it as a scaffold to grow on. Corneal stromal cells can ‘talk’ to cells in the patient’s damaged eye tissue to bring inflammation down and encourage the tissue to mend.
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Scientific summary
An innovative cornealised amniotic membrane bioengineered, from cell-banked limbal multipotent stem cells, for ocular surface reconstruction
Avoidable corneal blindness, stemming from limbal stem cell deficiency, is a major health concern aggravated by donor shortages and limited access to effective engineered corneal replacement alternatives. Current treatment modalities involve transplantation of limbal epithelial cells, which can be expanded ex-vivo on a vehicle such as amniotic membrane; however this is limited, particularly in bilateral involvement, due to chronic ocular donor shortages.
The team has discovered and characterised a novel source of expandable non-immunogenic multipotent stem cells located in the corneal limbal stroma, which produce mesenchymal stem cells, and readily transdifferentiate into corneal epithelium. Currently this property diminishes over long term culture. Their preliminary evidence indicates that when cultured on amniotic membrane, the culture conditions can be manipulated to transdifferentiated these cells to display characteristics of normal corneal epithelial and stromal cellular architecture. These cells therefore have great therapeutic potential and may be exploited to generate transplantable, replacement corneal epithelial sheets.
In persuit of this, the team is using its interdisciplinary stem cell and tissue engineering expertise to develop a methodology for establishing a specific stem cell bank. This will provide long-term use for novel ‘any and many patient’ corneal epithelial replacements. They are characterising these cells and the transdifferentiation process, at the morphological, phenotypic and molecular levels, and bioengineering a construct of amnion and stem cells to recreate the normal self-renewing corneal epithelial architecture. The success of the proposed work will provide the means to generate affordable and widely accessible tissue-constructs to benefit greater numbers of patients thereby addressing the global health concern of tackling avoidable corneal blindness.
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Research update
Progress is good and the team has shown that the stem cells grow well with Omnigen™. Now they’re working to improve the process and are planning a pre-clinical study to test safety and effectiveness.
The team has set up a company, NuVision, to help with their next steps to develop the technology and they have already attracted major corporate interest to help them get the treatment into clinical trials.
“Without the support of Fight for Sight this concept would not have developed to the commercial and therapeutic prospect it is today,” says Dr Hopkinson.
Results from this stage of the research are due in 2016. -
Publications
- Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A. (2014) Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors. Stem Cells 32 (6), 1380-1389.
- Branch MJ, Yu WY, Sheridan C, Hopkinson A. (2015) Isolation of Adult Stem Cell Populations from the Human Cornea. Springer, Methods in Molecular Biology: Stem Cell Protocols 2015 165-177.