- Jurkunas U. et al. (2022). Cultivated Autologous Limbal Epithelial Cell Transplantation: New Frontier in the Treatment of Limbal Stem Cell Deficiency. Am J Ophthalmol. 2022 Jul;239:244-268.
In the late summer of 2023, the first positive data from the Phase I study on the treatment of severe eye burns using cultured autologous limbal epithelial cell transplantation (CALEC) were published. This revolutionary stem cell treatment was successfully carried out on four patients. The research team from the Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, USA, was able to show in their study that their method was safe and well tolerated.1
Corneal scars and opacities are the fifth leading cause of blindness worldwide. They can be the result of limbal stem cell insufficiency, which can occur in various ways. In addition to infectious immunological, oncological, iatrogenic and congenital causes, eye burns also play an important role. In recent decades, various therapeutic strategies have been developed to replace the limbal epithelium with or without standard corneal transplantation surgery. However, there is an increased risk of rejection with allogeneic limbal transplants. Innovative treatment methods that circumvent this risk could provide a remedy.1
Currently, only a few treatment methods can be considered for limbal stem cell insufficiency. Various techniques for limbal stem cell transplantation have been described in ophthalmological studies. In the case of unilateral limbal stem cell insufficiency, the donor tissue can be taken from the other eye. In this way, an autologous limbal transplant is obtained that avoids the risk of rejection.
The situation is more difficult in the case of bilateral limbal stem cell insufficiency. In this case, an allogeneic transplant is required, which is associated with a high risk of rejection. This is due to the fact that the limbus is vascularised and contains antigen-presenting cells. Despite systemic immunosuppression, the survival rate of allogeneic limbal transplants can fall to as little as 50% after 5 years. If a penetrating keratoplasty is performed at the same time, the figures are even worse. Graft failure can be associated with considerable morbidity. A repeat transplant is often necessary. In addition to visual impairment, phthisis bulbi and glaucoma may occur.1
The research group from Boston, USA, conducted an intensive literature search on CALEC ("cultivated autologous limbal epithelial cell" transplantation) prior to their Phase I study. They drew on studies from all over the world and took into account previous experience with the treatment of limbal stem cell deficiency (LSCD) with cultured limbal epithelial cells (CLEC). Their analysis for the period between 1997 and 2020 found 21 studies on autologous and 13 studies on both autologous and allogeneic transplantation in humans. In the studies analysed, treatment with autologous CLEC transplants was 68.9% successful.
In their study, the research team improved the manufacturing conditions for this method. The researchers developed a novel manufacturing process in which only qualified and validated reagents were used. CALEC transplantation uses a bioengineered composite of ex vivo expanded autologous corneal epithelial cells and an FDA-approved amniotic membrane to reconstruct the ocular surface. The research team conducted the first clinical trial of CALEC transplantation for the treatment of LSCD in the US.1
The transplantation of human amniotic membrane (hAM) represents an important step forward in the treatment of severe diseases of the ocular surface. This method has been used for decades (since 1995) since its discovery 80 years ago. The hAM serves to mechanically support the reconstruction of the ocular surface and at the same time enables the re-epithelialisation and differentiation of the epithelium of the ocular surface. It promotes this process with growth factors, cytokines, and protease inhibitors. At the same time, scarring, and inflammatory processes are inhibited. After severe burns with alkali, this method showed an extremely high benefit.
Another advantage is that the amniotic membrane does not trigger rejection, as it does not express human leukocyte antigens (HLA)-A, -B or -DR antigens. For these reasons, the research group used the amniotic membrane as a substrate for CALEC. During the preclinical optimisation of the CALEC method, 132 CALEC transplants were produced from 37 different donor biopsy samples. The isolated cells were seeded on de-epithelialised human amniotic membrane and grown until the cells were confluent.1