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RPE Differentiation of iPSCs

Degeneration of the retinal pigment epithelium (RPE) cell layer is considered the major cause of age-related macular degeneration and replacement by iPSC-derived RPE cells may rescue disease phenotypes. There are, however, significant drawbacks with existing RPE differentiation protocols: they are lengthy, require difficult handling steps or complex cocktails of reagents overall, making them unattractive from a GMP perspective.

A blurred figure of a lab technician in a blue gown and face mask is seen working in the background of a sterile laboratory corridor. In the foreground, a wall-mounted panel with illuminated red, yellow, and green indicator lights is visible, suggesting a monitoring or alert system for the lab's equipment or processes. The lab environment is clean and well-lit, emphasizing a focus on safety and controlled conditions.

Catalent’s patent-pending approach simplifies RPE differentiation from iPSCs by combining streamlined neural induction with enhanced RPE specification under all-2D conditions. Fundamentally, this platform solely relies on an optimized sequence of specific media exchanges making it amenable to automation. The resulting cells have a high purity, express maturation markers after prolonged culture, and display functional features such as melanosomes, tight cell-cell contacts, as well as pronounced microvilli at their apical surface (see figures).

A high magnification, colorized microscopic image showing a cellular monolayer. The cells are outlined by a honeycomb-like network of green, red, and blue fluorescence markers. The green (BEST1) and red (ZO1) markers highlight the cell borders, indicating the presence of specific proteins, while the blue (DNA) stains the cell nuclei. The image has a scale bar indicating 25 micrometers, demonstrating the tight packing and structural organization of the cells. The vibrant colors distinguish between different cellular components, providing a detailed view of the cellular architecture.

Furthermore, iPSC-derived RPE cells can be efficiently recovered from a frozen state, allowing for the creation of cryopreservation banks with multiple patient doses. This platform is available for partnership or can be licensed separately.