Endothelial cell transplantation and growth behavior of the human corneal endothelium

Background: The human corneal endothelium has a limited proliferative capac ity in vivo. Until now it has only been possible to replace damaged endothe lium by transplantation of a donor cornea. After establishing methods for t he isolation and in vitro cultivation of human corneal endothelial cells, t ransplantation of these cells my be an alternative therapeutic option. Materials and methods: In this review methods for the in vitro cultivation of human corneal endothelial cells and their transplantation on the Desceme t membrane of donor corneas are described. Results: In vitro proliferation of human adult corneal endothelial cells wa s achieved by the development of defined cell culture conditions, including supplementation of culture medium with specified growth factors and substa nces. Dependent on the culture conditions, as well as independent of them, in vitro cultured endothelial cells showed phenotypic changes and different proliferative behavior. Thus, molecular biological examinations revealed a different expression pattern of growth factor receptors in fibroblastlike endothelial cells (dedifferentiated) compared to typical endothelial cells (differentiated). Moreover, the proliferative capacity of the cells differe d, dependent on their corneal location. Cells isolated from the peripheral part of donor corneas have a higher proliferative capacity than cells obtai ned from the central part. The propagation of corneal endothelial cells in vitro offered the possibility of their transplantation on donor corneas in an in vitro model. After transplantation, these cells formed a monolayer wh ose morphology and cell density depended on the differentiation of the cell s. DNA synthesis was predominantly detectable in cells of the corneal perip hery. Conclusions: Our findings are the basis of the following hypothesis: the pe riphery of the cornea represents a regenerative zone of the corneal endothe lium. The fact that early after transplantation corneal endothelial cells f orm a monolayer on the natural extracellular matrix (ECM), which shows cont act inhibition, suggests that inhibitory factors are released by the Descem et membrane that influence the proliferation of the cells. Further studies on the regulation of the proliferation and differentiation of human corneal endothelial cells in vitro and after transplantation might offer the possi bility to establish a selective procedure for the treatment of corneal endo thelial cell loss in the near future.