Cellular Models of Neurodegenerative Disease Derived from Human Cells
Directly-converted human fibroblasts make neurons and glia suitable for drug screening
Studying disease in living cells relevant to human neurodegenerative diseases has historically relied on making induced neuronal progenitor cells (iNPCs) from post-mortem tissue, or on making induced pluripotent stem cells (iPSCs) from skin fibroblasts. iNPCs or IPSCs can then finally be turned into the tissue of interest, be it neurons, astrocytes or oligodendrocytes, by using a cocktail of different growth factors.
Post-mortem tissue is in short supply and the isolated tissue is unhealthy, which means that the cells derived from it have variable properties that can confound experiments. The iPSC method is time-consuming and highly inefficient. This direct conversion technology developed by researchers at The University of Sheffield is an improvement on both methods because it is faster, more reproducible and more efficient.
The researchers can generate consistent, functional iAstrocytes, iNeurons or iOligodendrocytes in as little as four weeks from the time the human skin sample is isolated. They have shown that the iAstrocytes made by direct conversion have similar toxic properties towards neurons in a co-culture system, compared to astrocytes derived from post-mortem iNPCs [Meyer et al (2014); PNAS, 111 (2), pp 829-832, PMID:24379375].
The research team are now exploiting the iAstrocytes, iNeurons and iOligodendrocytes made using this direct conversion method to study Alzheimer’s disease, Parkinson’s disease and motor neuron disease at the University of Sheffield on research grants and through collaborative/contract research with industry.
- Faster to make
- Absence of clonal variation
- Availability of a cell population that can be expanded and stored
- Higher efficiency of conversion
- Reproducible results
- More ‘memory’ of the original cell type/ageing signature
- Production of cellular models of disease for research studies and assessing the activity of potential new drugs
- Cell therapy- replacing lost or malfunctioning cells in the human body in situ
- Collaborative research: mechanisms of disease
- Contract research: drug screening
- Know-how based
- Development partner
- Commercial partner