Neural Stem Cells Used to Reverse Multiple Sclerosis Symptoms and Promote Neurogenesis in Mouse Models

By:Shamim Gol

Main Ideas/Background

Multiple sclerosis is an autoimmune inflammatory disease that affects the CNS (central nervous system) of over 2.5 million people over the world. During the disease process, the individual’s own immune system attacks the oligodendrocytes present in the CNS. Oligodendrocytes are responsible for myelinating the neurons present in the CNS and when these cells are damaged, lack of myelination results in axon damage and insufficient delivery of signals to and from the CNS. With recent advances in the field of regenerative  medicine, researchers have been interested in utilising neural stem cells (NSC) and Mesenchymal stem cells (MSC) in treating neural diseases and injuries. These cells can proliferate fast and regenerate tissues. Can stem cell studies provide promising treatments for neurodegenerative disease like MS?

Methods

        This study focused on mice as a model organism to investigate the effects of injecting stem cells on EAE (experimental autoimmune encephalomyelitis)multiple sclerosis disease.This model of MS is the most common model of the disease used in animal models. Previously isolated MSCs were cultured and induced towards differentiation into NSCs using induction media. The NSCs were then differentiated into oligodendrocytes (ODCs). Flow cytometry analysis, qRT-PCR and western blot was used to make sure these cells expressed appropriate markers. The cells were then labelled with PKH26 cell membrane dye and transplanted into affected mice via tail-vein injection and analysed for expression of inflammatory and neurotrophic markers post-transplantation

 

 Results

        After 14 days, the mice were sacrificed and the CNS tissues were analysed. Results showed that Neural stem cell (NSC) transplantation and MSC transplantation both improved MS symptoms, with NSC showing a better improvement. Histochemical and immunofluorescence staining of brain and spinal cord tissue showed reduced immune infiltrates (T-cells) which implied an anti-inflammatory response. Staining of the CNS tissue with LFB ( a type of dye) also showed transplantation had induced remyelination. Staining of the neurotrophic factors also illustrated that NSCs have differentiated into other types of neural cells and has improved neurogenesis and has down-regulated inflammatory genes.

Figure 1 (2 from the article) compares the clinical symptoms of EAE before and after transplantation and how these symptoms have improved after transplantation.

Figure 2 (4 from the article) shows immunofluorescence assays conducted and how inflammatory response has decreased in CNS after stem cell transplantation.

Key Terms

EAE MS: Experimental autoimmune encephalomyelitis is the most common model of CNS: neurodegenerative diseases like MS used in animal models for studying  

NSC: Neural stem cells

MSC: Mesenchymal stem cells are type of stem cells present in different tissues that can be differentiated into other types of stem cells or cells

Thinking outside the box

Neurodegenerative diseases are affecting millions of people worldwide and the treatment for these diseases are often expensive and have a wide range of side effects. Stem cells and their ability to proliferate and differentiate into any type of cell or tissue gives them a huge potential for developing novel therapeutics. Using an individual’s own cells can also provide a personalised therapy plan that lessens the risks of severe immune response after therapy.

References

Brown, C., McKee, C., Halassy, S. et al. Neural stem cells derived from primitive mesenchymal stem cells reversed disease symptoms and promoted neurogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Stem Cell Res Ther 12, 499 (2021). https://doi.org/10.1186/s13287-021-02563-8

 

Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem cell research & therapy, 10(1), 68. https://doi.org/10.1186/s13287-019-1165-5

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