Towards a clinical-trial-in-a-dish: Validating an animal product free stem cell-derived 3D model of Alzheimer’s disease for drug discovery

Working with industrial partners, Mattea will replace the use of Matrigel, derived from a mouse sarcoma model, with an animal-free peptide hydrogel scaffold developed with previous NC3Rs funding and characterise its use in an in vitro model of neurodegeneration. The characterisation studies will involve various cellular readouts and drug screening.

This award was made as part of the 2024 non-animal derived product validation grants supported with funding from the Department for Science, Innovation and Technology (DSIT).

Worldwide over 50 million people are living with Alzheimer's disease (AD). Currently there is no effective treatment for AD and most clinical trials have so far failed. This is partly due to the lack of effective in vitro and animal models of AD that could be used in drug discovery prior to testing in humans. 

This project aims to address this unmet need by developing an advanced in vitro animal product-free cellular model of AD, which will:

• Include the two most abundant cell types of the brain, neurons and astrocytes, derived from induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells of heathy controls and people living with AD
• Recapitulate key AD features such as excessive levels of amyloidβ-42 and hyperphosphorylated Tau
• Be grown in 3D as this recapitulates the pathophysiology of AD better than cells cultured in 2D. Because 3D culture relies on the use of the animal-derived product Matrigel, here we will test an alternative to Matrigel by using a novel animal product-free selfassembling peptide hydrogel (SAPH).
• Support drug discovery through a high-throughput compatible format

The main aims of this project are to: 
Aim 1: Characterize iPSC-neurons cultured in 3D in Matrigel vs SAPH

Aim 2: Develop a 3D model of co-cultured iPSC-neurons and iPSC astrocytes in SAPH

Aim 3: Provide proof-of-concept for the new model in high throughput drug screening

Our long-term vision is to develop an in vitro clinical-trial-in-a-dish model for AD made up of cells derived from iPSCs reprogrammed from somatic cells from patients and that could be used in the future as a platform for pre-clinical drug discovery and personalised medicine.