Neural lineage differentiation of human pluripotent stem cells: Advances in disease modeling

June 26th, 2023
Neural cell subtype differentiation from human pluripotent stem cells. The first step of neural cell differentiation is neural induction to generate neuroepithelial cells, usually by the dual SMAD inhibition method. Specific neural progenitors can be generated by tuning different signaling pathways such as Sonic Hedgehog, Wingless/integrated, retinoic acid, and bone morphogenetic protein. Neural progenitors can then be directed to become mature neurons through induction with neurotrophic factors such as brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor or derived into glial progenitors through treatment with the growth factors fibroblast growth factor 2 and epidermal growth factor. Glial progenitors can give rise to either astrocytes or oligodendrocytes. BDNF: Brain-derived neurotrophic factor; GDNF: Glial cell line-derived neurotrophic factor. Credit: World Journal of Stem Cells (2023). DOI: 10.4252/wjsc.v15.i6.530

Brain diseases affect one in six people worldwide. These diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer's disease. Recent advancements in tissue-engineered brain disease models have overcome many of the different shortcomings associated with the various animal models, tissue culture models, and epidemiologic patient data that are commonly used to study brain disease.

One innovative method by which to model human neurological disease is via the directed differentiation of human pluripotent stem cells (hPSCs) to neural lineages including neurons, astrocytes, and oligodendrocytes. Three-dimensional models such as brain organoids have also been derived from hPSCs, offering more physiological relevance due to their incorporation of various cell types. As such, brain organoids can better model the pathophysiology of neural diseases observed in patients.

In a new review published in World Journal of Stem Cells, the researchers emphasize recent developments in hPSC-based tissue culture models of neurological disorders and how they are being used to create neural disease models.

This review discusses recent advances in the field of disease modeling using human-induced pluripotent stem cell-derived neural cell types as well as organoids. It also discusses challenges that exist with current approaches, in addition to considerations for possible improvements that will further advance the field of disease modeling.

More information:
Yuan-Wei Yan et al, Neural lineage differentiation of human pluripotent stem cells: Advances in disease modeling, World Journal of Stem Cells (2023). DOI: 10.4252/wjsc.v15.i6.530

Provided by World Journal of Stem Cells