UCL Institute of Ophthalmology


Cell Models of Disease

Cells can provide superior models for disease when compared to animal models.

With the advancement in stem cell technologies, cell modelling has become a new way to investigate human disease in humans. Cells can be taken from patients with the disease of interest in the form of a skin biopsy, blood, or urine and ‘reprogrammed’ into stem cells. These stem cells can then be made into any cell in the body, a process known as differentiation. As we are interested in the Retinal Pigment Epithelium (RPE) in bestrophinopathies, these stem cells are differentiated into RPE. These RPE cells in a dish behave in the same way as the RPE cells at the back of the patient's eye. Therefore, we can use these to investigate what is happening in the disease and attempt to find treatments. 

Schematic showing stem cell creation from patient skin biopsy, differentiation into RPE cells and using these RPE cells for personalised medicine, drug discovery/screening, disease modeling and mutation correction for transplantation.

Advantages of cell models: 

  • Same cells as the patient – act in the same way. 

  • Can study the effect of different mutations in different patients 

  • Infinite production of cells. 

  • Storable – cells can be kept in liquid nitrogen for extremely long periods of time. 

  • Maintains cell-to-cell interactions. 

  • Can look at early stage disease processes 

  • Cells can be used to ensure therapies work prior to putting into patient 

Disadvantages of cell models: 

  • Loss of cell-to-environment interactions – cells are taken out of the environment for which they would usually be present in. This can influence the modelling diseases associated with how the cell of interest interacts with the surrounding environment in the body. 

  • Specialised techniques to establish cell line and stem cell stocks. 

  • Sometimes cells just aren’t happy to grow out of the body. 

Cell models of disease are being increasingly used to model bestrophinopathies. Carter et al, have used stem cells from ADVIRC patients to model the disease in the dish. This research has shown that a mutation in the BEST1 gene results in the BEST1 protein being mis-localised within the RPE cells, leading to disease. This can be seen by this image taken from that paper. Usually the labeled BEST1 protein (green) can be seen only one the basal membrane of the RPE (top image). Whereas, in the patient cells it can be seen all over the RPE cell membrane (bottom image).

Image of RPE cells labeled for BEST1 protein (green). Top = healthy RPE cells. Bottom = Patient diseased RPE cells.