MSCs for Alzheimer’s disease

MSCs for Alzheimer’s disease

According to the World Health Organization (WHO), dementia is mainly seen in older people though it is not normally part of the aging process. There is a decline in thinking, memory, behavior, and the ability to perform everyday activities. Across the globe, there are 10 million new cases every year of dementia with the most common form of dementia being Alzheimer’s disease (AD: accounting for 80% of all dementia diagnoses)! The effects of the disease range from psychological to physical to social and economic-for both the patients and their caretakers. An annual cost of $500 billion is the estimated expenditure incurred due to AD. While cholinesterase inhibitors that are prescribed as current treatment can allow an enhanced quality of life when given at the correct time, the course of the illness or the rate of decline remains to be addressed (Weller and Budson, 2018).

The ability of mesenchymal stem cells (MSCs) to modulate the immune responses along with their ability to differentiate and present minimum rejection has made them be explored as a treatment option for AD (Zhang et al, 2020).

As the major pathology of AD involves the abnormal deposition of amyloid-β (Aβ) proteins; one aspect of toxicity is due to the oxidative stress induced by the free radical production by Aβ. Recent work published in 2019 by Yokokawa and team showed the ability of MSC transplantation in AD model mice (APdE9) to improve the damage due to oxidative stress and modify the microglial cells. The transplantation of MSC via the tail vein in the animals lowered the levels of a microglial marker called Iba1 in the cortex and lowered the levels of ameboid shaped microglia. The deposition of Aβ in the cortex and hippocampus were lowered while microglial Aβ uptake and clearance were increased. The coculture of MSCs with the mouse microglial cell line MG6 showed a switch in M1 to M2 macrophage phenotype to also lower proinflammatory cytokine production. As shown by the Morris water maze test, the spatial memory of the animals was also improved by the MSC treatment.

A review by scientists Ge and team (2018) discussed that MSC‐based treatments improved the cognitive performance in 225 animals in 9 preclinical studies. The various aspects of the Morris water maze test such as escape latency and the number of platform crossings were improved by MSC treatment. Thus, the authors concluded that cell therapy using MSCs can address the cognitive deficits in AD models to show their promise for treating this truly “degenerative” disease.

References:

https://www.who.int/news-room/fact-sheets/detail/dementia#:~:text=Worldwide%2C%20around%2050%20million%20people,dependency%20among%20older%20people%20worldwide.

Weller, J., & Budson, A. (2018). Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research7, F1000 Faculty Rev-1161. https://doi.org/10.12688/f1000research.14506.1

Lu Zhang, Zhi-fang Dong, Jie-yuan Zhang (2020) Immunomodulatory role of mesenchymal stem cells in Alzheimer’s disease, Life Sciences 246: 117405, ISSN 0024-3205: https://doi.org/10.1016/j.lfs.2020.117405.

Yokokawa, Kazuki, et al. ‘Transplantation of Mesenchymal Stem Cells Improves Amyloid-β Pathology by Modifying Microglial Function and Suppressing Oxidative Stress’. 1 Jan. 2019: 867 – 884.

Ge, M., Zhang, Y., Hao, Q., Zhao, Y., & Dong, B. (2018). Effects of mesenchymal stem cells transplantation on cognitive deficits in animal models of Alzheimer’s disease: A systematic review and meta-analysis. Brain and behavior8(7), e00982. https://doi.org/10.1002/brb3.982

 

 

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