Stem Cell Transplantation for Ocular Surface Reconstruction

Since 2007, the Laboratory of Ophthalmology (UA) has collaborated with the Centre for Cell Therapy and Regenerative Medicine and the Department of Ophthalmology, UZA on the project “Translational research in ophthalmology - regenerating the anterior cornea though standardized limbal stem cell transplantation". This research funded by theFRO, Societie Philanthropie Royale, Bakeland Foundation and IWT TBM has completed its phase I/II trial with a 67% success rate and a Phase II multicenter study was funded in January 2014 in collaboration with the University Hospitals of Brussels and Gent. Through transplantation of corneal epithelial stem cells expanded ex vivo on amniotic membrane scaffolds, a treatment option is provided for patients with damaged ocular surfaces due to chemical or thermal burns,  genetic diseases such as aniridia, autoimmune disorders etc. that leave the cornea scarred and vascularized. The treatment reverts the cornea to an avascular state improving subsequent corneal graft retention rates.

 

 

 

 

 

 

Tissue engineering in ophthalmology: regenerating the anterior cornea using self-aligning human recombinant collagen nanoscaffolds and corneal epithelial stem cells.

Recent research has proven the feasibility and the advantages of cultivated limbal stem cell transplatnation using the human amniotic membrane (HAM) as a scaffold. However, the HAM, being of biological origin maintains strong inter- and intra-donor variations, and is therefore difficult to standardise. It also holds potential health risks for the acceptor. The goal of this research is to develop bio-synthetic membrane to replace the use of HAM in corneal tissue engineering. The recent introduction of the Self-Aligning Human Recombinant Collagen makes the development of a biosynthetic, transparent and mechanically stable membrane possible, onto which LESC can be cultured to regenerate the anterior cornea. We intend to develop a membrane with improved transparency, higher mechanical stability, better bio-integration and a reduced microbiological susceptibility. The effect of collagen cross linking and surface modifications will contribute in the development of an optimized biosynthetic scaffold. This research is funded by the FRO, FWO and Euronanomed (ERAnet) in collaboration with partners from Israel, Sweden and Lithuania.

 

Development of a biomimetic cornea: combining 3D printing and stem cell technologies.

‚ÄčEach year, there are up to two million new cases of monocular corneal blindness due to ocular trauma, corneal ulceration and a wide variety of inflammatory and infectious diseases. Often, the damage is not limited to the anterior stroma, but affects the deeper layers of the cornea leading to scarring and corneal blindness. However, only 120,000 corneal transplants are carried out each year due to donor shortages, leaving about ten million untreated patients globally. The main reason for this discrepancy is the high shortage of suitable donor corneas. Other limitations to transplantation of a donor cornea include difficulty in matching the donor cornea with respect to the recipient in terms of biology, geometry and biometry, plus, despite donor screening within existing cornea banks, there is always a risk of disease transmission. These limitations indicate a need to develop alternatives to the use of donor corneas.  All currently available artificial corneas present a high risk of serious complications such as rejection, extrusion, retroprostethic membrane formation, calcification, glaucoma, retinal detachment and failure or rejection. Their use is therefore limited to a last resort in the high risk corneal transplant group where transplantations have previously failed.              
The aim of this project is to address the need for an alternative by developing biomimetic corneas using host stem cells, recombinant human collagen and 3D printing thereby creating customized cornea grafts. Our partners include the Department of Product Development (University of Antwerp), Departement Materiaalkunde (MTM) and Production Engineering at Katholic University of Leuven. This project is funded by the FWO, Flanders.


 

Tissue Engineering Corneal Endothelial Cell Sheets

One of the causes of corneal blindness is endothelial dysfunction. Different factors can cause a drop in the number of corneal endothelial cells below a certain threshold that ascertains the adequate function of the endothelial monolayer. Current solutions for this pathology include transplantation of a donor corneal endothelial layer to the affected eye (Endothelial Keratoplasty). However, the global issue in corneal transplantation nowadays is the low donor to patient ratio. This shortage of donor corneas is the main drive in corneal tissue engineering research. The overall aim of this project is to optimize ex vivo expansion of functional corneal endothelium for the treatment of corneal endotheliopathy. We aim to tissue engineer corneal endothelial cell sheets for corneal regeneration and hence improve the current donor to patient ratio. The expected outcome is a functional corneal endothelial cell graft, which will be validated in a rat model of corneal endotheliopathy. This ground breaking research will result in a paradigm shift and completely change the current approaches towards corneal tissue banking and transplant surgery. Tissue engineered corneal endothelium, will potentially allow scale up and address cornea donor shortages in a refined manner, progressing the state-of-the-art to a proof-of-concept (TRL 4), in preparation for a phase I human clinical trial.

CLP-PEG scaffold development: towards conjunctival tissue engineering

The human body is predisposed to heal itself after injury. But what if the damage is so severe that the limit of its regenerating capacity is reached. What’s next? How far are we and can we push these boundaries? Is there a point of no-return? Unfortunately, the answer to this last question is ‘yes’. In patients with severe ocular surface damage, the injury often leads to abnormal scar formation and a depletion of stem cells. Ocular stem cells are able to grow into specialized cells forming important layers of the eye. For example, some grow into epithelial cells which form the outermost barrier protecting the surface of the eye some grow into goblet cells which secreate lubricating components into the tear film. The combination of scar formation and epithelial cell loss results in a hostile environment, which can be experienced by patients through symptoms of discomfort, pain, blurred vision and even blindness.

 

With the introduction of tissue engineering – an emerging field that uses living cells grown on scaffolds to create living tissues – scientists are pushing the boundaries of science to repair seriously damaged tissues. Over the past year, significant research efforts have been made to regenerate a transparent cornea (figure 1, green) to rectify vision loss and blindness. Clinical trials have been performed in which stem cells that were grown on a biological membrane in the lab, were transplanted onto the ocular surface. Interestingly, the success rate of the treatment correlated with whether patients had a functioning conjunctiva (figure 1, blue) or not. This observation has contributed to the heightened interest towards conjunctival regeneration, which is also the focus of this project. Moreover, a tissue engineered conjunctival substitute could provide a solution for the approximately 175 million people worldwide suffering from conjunctival disorders.

 

Figure 1: A) Front view of the ocular surface and B) A cut section through the front of the eye. Green and blue lines indicate the cornea and conjunctiva, respectively.

In this project, a novel bio-synthetic scaffold is explored to determine its potential as a substrate for tissue engineering the human conjunctiva. This potential scaffold consists of small peptides (or building blocks) that self assemble into a structure that resembles collagen. Collagen is a major structural component of the human conjunctiva and forms the base on which the epithelial cells grow and function. The two main questions that we intend to answer with our proposed project is: (I) ‘Can we grow human conjunctival cells on these bio-synthetic, collagen-like scaffolds?’ And (II) ‘Would such tissue engineered conjunctiva be able to function correctly?’.

 

 

 

Contact

Nadia Zakaria
Tel.
+32 3821 4066
Universitaire Ziekenhuis Antwerpen, Center for Cell Therapy and Regenerative Medicine - U113
Wilrijkstraat 10
2650 Edegem, Belgium

Corneal Regeneration: Using Stem Cells and 3D Printing to Tackle Corneal Blindness

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