The overall EYEFORTX-2 project objective:

Limbal stem cell deficiency (LSCD) affects 3.3 out of 100,000 people in the EU (about 350-500 in the Czech Republic) and is often leading to a total blindness. The mechanism of the disease, which
The overall project objective:can be triggered by injury, such as chemical or thermal  burn or have genetic etiology is shown in Fig. 1.

Figure 1. Limbal stem cell deficiency: Conjunctival epithelium extends over corneal surface (red  arrows). Such condition originates as a result of progressive depletion or dysfunction of limbal
stem cell population and leads to significant loss of vision or blindness.

Our aim is to restore the vision of patients suffering from both unilateral and bilateral forms of  the disease.  Developing cell-based therapy, i.e. the Advanced Therapy Medicinal Products (ATMP) with the presence of stem cells, requires a considerable funding, experienced top team, facilities such as  tissue establishment and clean rooms, a top-quality equipped eye clinic, and rapid transfer of new  technology into practice. Any delay in the chain: basic research -> applied research -> product  development and approval -> clinical application increases the probability of ending up with
obsolete experimentally developed treatments. The treatment consists of replacing limbal tissue with the stem cells for the corneal epithelium. Only the presence of stem cells at the limbus can permanently assure a normal homeostasis, i.e. a transparent cornea, over which the opaque vascularized conjunctiva does not overgrow. The principle is schematized in Fig 2.

Figure 2. Treatment options for unilateral and bilateral limbal stem cell deficiency (LSCD). In unilateral LSCD, there is the option for direct transplantation of limbal tissue (blue arrow), retrieved from the paired healthy eye (risk and disadvantage of causing LSCD), or from a living-related donor (need for immunosuppression). Another possibility is the Cultivated Limbal Epithelial Transplantation (CLET), a retrieval of a very small piece of limbus from the healthy patients' eye and its ex vivo culture to produce a cell sheet which will be used for grafting. In bilateral LSCD, there are no autologous LECs to retrieve and one option is to retrieve and culture Oral Mucosal Epithelial Cells (OMECs) ex vivo, and then to transplant them onto corneal surface (cultivated oral mucosal epithelial transplantation, COMET). Alternatively, other autologous stem cells, e.g. hair follicle bulge-derived cells, can be used for such procedure.

The major goal of the project is to speed up the development of ATMP as much as possible and to start with treatment of unilateral and bilateral. One of the prerequisites for this rapid pace is the continuity of the results already obtained and the previous cooperation of the partners of the entire project team. This proposal is a direct continuation of the 'EYEFORTX-2' project, which has received an 'excellent' evaluation and whose results will be partly used in this project. The majority (65%) of innovation is already available from the latest call from Norwegian grants and  follow-up work; some of the results have been further improved and, together with the newly acquired results, will be transferred to the preclinical (tissue facility – eye and Eye bank  Kralovske Vinohrady University Hospital) and clinical practice (transplantation ophthalmological department of Kralovske Vinohrady University Hospital).

EYEFORTX-2  Project Outputs / News

Papers

Smeringaiova I, Utheim TP, Jirsova K. Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review. Stem Cell Res Ther. 2021 Oct 30;12(1):554. doi: 10.1186/s13287-021-02611-3. PMID: 34717745; PMCID: PMC8556978. IF: 6.832 (2020), Q1 in CELL & TISSUE ENGINEERING, CELL BIOLOGY, MEDICINE, RESEARCH & EXPERIMENTAL 

 

Review that describes the possibilities of the preparation/culture of corneal cells for transplantation purposes. image Corneal endothelial cells cultured for 22 (A) and 25 days (B). A: satisfactory cell morphology, B: cells undergoing endothelial-to-mesenchymal transformation- unsatisfactory morphology.