Abstract

DO.19.01

Stem cell-based therapeutic approaches for retinal disorders

Udo Bartsch

Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Hamburg-Eppendorf, Hamburg

Objective
Stem cells are multipotent cells with the ability to self-renew. They are therefore considered as promising candidate cells to establish cell-based therapies for the treatment of various retinal disorders. In principial, stem cells might be used to replace degenerated or dysfunctional cell types (cell replacement strategy) or to target therapeutically relevant gene products to diseased tissues (ex vivo gene therapy).
Methods
Freshly isolated retinal cells were injected into the subretinal space of adult wild-type mice or mouse models of degenerative retinal disorders to analyze whether grafted cells are capable to integrate into healthy or dystrophic retinas and to differentiate into photoreceptors. Bicistronic lentiviral vectors encoding a “gene of interest” and a reporter gene in fusion with a resistance gene were used to express therapeutically active gene products in neural stem cells.
Results
Freshly isolated and subretinally grafted retinal cells integrated into the outer nuclear layer of healthy or dystrophic adult retinas where they differentiated into apparently normal and fully mature rod photoreceptor cells. Lentiviral vectors allowed the efficient derivation of genetically engineered, pure neural stem cell cultures or clonal stem cell lines stably expressing therapeutically relevant gene products.
Conclusions
Results suggest the principal feasibility to replace degenerated or dysfunctional photoreceptor cells in adult dystrophic retinas by cell transplantation. Furthermore, genetically engineered neural stem might provide a tool to develop a stem cell-based intraocular delivery system for a continuous and long-lasting application of therapeutically relevant gene products.

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