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Powerful approaches to study neurodegeneration

Induced pluripotent stem cells (iPSCs) make the idea of “disease in a dish” become a reality! [1]. iPSC-based models offer researchers the possibility to develop a more in-depth understanding of the pathological mechanisms involved in human diseases, especially neurological diseases. Currently almost all types of neural cells can be derived from iPSCs, offering a more powerful and unprecedented cellular model of study [2, 3].

There are many advantages of using iPSCs, including their human origin, easy expandability, ability to differentiate into any cell type from all three germ layers while avoiding the ethical issues associated with embryonic stem cells and the possibility of obtaining iPSCs directly from patients [1, 2, 4].

Due to their ability to differentiate into almost all types of neural cells (including but not limited to neural stem cells, neurons, astrocytes, oligodendrocytes and microglia), iPSCs represent a great opportunity to focus on the pathological mechanisms driving specific neurodiseases. Indeed, the possibility of using iPSCs derived from patients with familial or a sporadic form of such a disease is a valued resource for studying them.

Genome-editing techniques have also allowed the generation of isogenic iPSCs which have the same genetic background, differing only in the mutation of interest [2]. This gives a good insight into studying the impact of that particular single mutation on the disease progression.

Interestingly, the setup of co-cultures has recreated a more faithful in vitro model of cellular function and dysfunction, mimicking the natural interactions between cell populations, resembling the nervous system more accurately [2]. Additionally, 3D neuronal organoids obtained from iPSCs can recapitulate some neuropathological phenotypes such as mid-fetal development, and the epigenomic signatures of the human fetal brain [5, 6]. Recent developments in 3D tissue engineering and microscale technologies have also led to the creation of “brain-on-a-chip” models [7]. One of the main advantages derived from them is the possibility of generating multiple organs from the same cells [2].

These extraordinary tools have therefore improved the potential of in vitro models developed using iPSCs for studying neurological disease mechanisms and developing potential therapies.

 

Written by Rosa Loffredo, European Collection of Authenticated Cell Cultures (ECACC)

 

Further information:

ECACC distributes iPSCs through both the EBISC and HipSci collections which give researchers a wide choice of over 1,500 iPSC lines derived from male and female subjects of various ages and represent a wide variety of rare and more prevalent diseases.

1. Shi, Y., et al., Induced pluripotent stem cell technology: a decade of progress. Nature Reviews Drug Discovery, 2017. 16(2): p. 115-130.

2. Mohamed, N.-V., et al., One Step Into the Future: New iPSC Tools to Advance Research in Parkinson's Disease and Neurological Disorders. Journal of Parkinson's disease, 2019. 9(2): p. 265-281.

3. Li, L., J. Chao, and Y. Shi, Modeling neurological diseases using iPSC-derived neural cells. Cell and Tissue Research, 2018. 371(1): p. 143-151.

4. Huang, C.-Y., et al., Human iPSC banking: barriers and opportunities. Journal of Biomedical Science, 2019. 26(1): p. 87.

5. Camp, J.G., et al., Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proceedings of the National Academy of Sciences, 2015. 112(51): p. 15672.

6. Luo, C., et al., Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain. Cell Reports, 2016. 17(12): p. 3369-3384.

7. Bang, S., et al., Brain-on-a-chip: A history of development and future perspective. Biomicrofluidics, 2019. 13(5): p. 051301-051301.