Stem Cells

Studying Age-related Neurological Disease with induced Pluripotent Stem Cells | Part 2 | Generating iPSCs

Posted on 27 May 2021

Last week I published Part 1 of this article series, which looked at the global impact of neurological disease, the challenges faced in trying to study these conditions, and the introduction of induced pluripotent stem cells to build disease models.

But, what exactly are induced pluripotent stem cells, and why are they important?

In 2007, Dr. Shinya Yamanaka, and his team in Japan, injected viral transport particles containing four proteins, known as the Yamanaka factors, into adult cells. These Yamanaka factors were found to drive the process of turning adult cells back into a pluripotent, undifferentiated state.

One of the amazing things about this process is that it can be done using almost any type of cell. iPSCs also have the ability to turn back into any cell type [1].

This means that scientists can take some very easily accessible cells, skin cells for example, and then, using these Yamanaka factors, turn them back into stem cells. These pluripotent stem cells which can then be differentiated into brain cells, or any other type of cell type which is difficult to obtain.

These cells can then be used to simulate a certain disease to determine its unique mechanisms, or be used as a dummy for running potential drugs or interventions on to see how they respond. This is known as a disease model.

The legendary Dr. Yamanaka with his lab team. Source: Gladstone Institutes

Another crucial benefit to using iPSCs to build disease models, is that they can be derived from the cells of individuals with a specific disease. This means that the resulting disease model contains the exact genetic defect and identical genetic background of the individual the cells have come from, allowing for a model that far more accurately represents the specific disease [2]. Therefore, patient samples can be used to develop iPSC lines that host pathogenic mutations.

Subsequently, using gene editing techniques, such as CRISPR/Cas9, iPSC lines can be genetically modified to edit a particular genetic loci and ascertain the relative contribution of a specific mutation to a disease characteristic. This allows the examination of the disease in greater detail and also enhances the capacity to correct the desired cells for the production of novel cellular therapies [2].

3D Rendering Crispr DNA Editing. Image Credit: Nathan Devery / Shutterstock

Since this important discovery by Yamanaka and his team, developments to efficiently produce iPSCs from somatic cells have continued at a steady pace.

Keep an eye out for Part 3, where we will be talking about how to use iPSCs to build the ultimate disease model… artificial brains!


References

[1] Barral, S. and Kurian, M. A. (2016) ‘Utility of induced pluripotent stem cells for the study and treatment of genetic diseases: Focus on childhood neurological disorders’, Frontiers in Molecular Neuroscience, 9(SEP2016), pp. 1–11. doi: 10.3389/fnmol.2016.00078.

[2] Sterneckert, J. L., Reinhardt, P. and Schöler, H. R. (2014) ‘Investigating human disease using stem cell models’, Nature Reviews Genetics. Nature Publishing Group, 15(9), pp. 625–639. doi: 10.1038/nrg3764.


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