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Latest innovation in retina models brings a fully characterised Retina Pigment Epithelium (RPE)

Our latest innovation is an iPSC-derived RPE model, developed to complement the neural retina model (retinal organoids). The RPE cells in the model form a polarised monolayer and express cell specific RPE markers (e.g. BEST1 and TYRP1). They are also fully functional allowing phagocytosis of photoreceptor outer segments, forming a tight epithelial barrier and secretion of growth factors.

Why develop an RPE model?

Retinal pigment epithelium (RPE) cells play a vital role in the retina by forming the outer blood-retinal barrier and maintaining photoreceptor and visual function. As a result, RPE degeneration and dysfunction is a prominent feature of many retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy and Stargardt Disease. Despite the significant progress in understanding the molecular basis of these diseases, there are still many challenges to developing effective treatments; one of the reasons being the lack of suitable in vitro models.

Newcells Biotech is working to reverse this trend, developing in vitro tools for predictive evaluation of efficacy and toxic potential of drug and gene therapy products in the retina. We have built a range of models and assays that mimic the physiology of the human retina. Our latest innovation is an iPSC-derived RPE model, developed to complement our neural retina model (retinal organoids). The retinal pigment epithelium cells are derived from the same iPSC line as the retinal organoids, and therefore have the same genetic background allowing more comprehensive studies to be performed on both the neural retina and the RPE.

Existing models such as primary cells, cell lines, tissue explants, and animal models all have their limitations, making it difficult to extrapolate to the human condition with high efficacy and predictivity. The complexity of the human retina has made it particularly challenging to find a predictive in vitro model. This is where iPSC-derived RPE models and retinal organoids offer a major breakthrough as they can be used in combination to assess the effect of a new treatment on both the RPE and neurosensory retina. Our human models are complex and well-characterised to provide key information through careful study design.

RPE model characteristics and applications

We have successfully developed a reproducible differentiation protocol from human derived iPSC lines to RPE cells with the structural and functional characteristics of human RPE such as the formation of a polarised monolayer and the expression of cell specific RPE markers (e.g. BEST1 and TYRP1). The model also recapitulates various known functions of human RPE cells such as phagocytosis of photoreceptor outer segments, formation of a tight epithelial barrier and secretion of growth factors.

Cell supply and rolling production

We have the capability to generate large numbers of cells through our regular batch production that undergoes quality control testing. As a result, Newcells produces a continual supply of fully characterised cells to provide consistent quality for our clients and their projects.

Disease modelling  and gene therapy

The most significant advantage of this model over traditional ones is the ability to accurately model diseases that affect the retina by using patient-derived or gene-edited iPSCs. Our RPE model can also be used for the study of drug-induced toxicity in context that is relevant to human biology. This is particularly important since toxicity studies that use animal models may differ from clinical outcomes in humans.

Moreover, our RPE model is particularly useful for evaluating gene therapy vectors for eye disease. Gene therapy in ocular diseases, has shown tremendous progress in recent years with Adeno-associated virus (AAV) vectors being the most widely used vectors. At pre-clinical stages, AAV vectors are evaluated to check for efficient targeting of target cells and intra-cellular expression of transgene, efficacy of gene delivery and possible toxicity. Our iPSC-derived models offer the possibility of looking at off-target effects and efficacy in complementary human cell models of the neural retina and the RPE.

In summary, Newcells iPSC-derived RPE model offers an innovative approach to in vitro ocular drug discovery and development. With the ability to accurately mimic the structural and functional characteristics of human RPE, Newcells provides a more reliable platform with a set of tools for drug discovery and gene therapy vector evaluation. Moreover, our robust production process with the capability to generate a large number of confluent RPE monolayers, makes our model particularly useful for high-throughput drug screening. Newcells RPE model proves to be an invaluable tool in accelerating the development of safer and more effective drug candidates and gene therapy products for retinal diseases.

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28th April, 2023



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