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Review
. 2022 Oct 6:15:1011225.
doi: 10.3389/fnmol.2022.1011225. eCollection 2022.

Mesenchymal stromal cells for the treatment of Alzheimer's disease: Strategies and limitations

Shobha Regmi  1 , Daniel Dan Liu  1 , Michelle Shen  1 , Bhavesh D Kevadiya  1 , Abantika Ganguly  1 , Rosita Primavera  1 , Shashank Chetty  1 , Reza Yarani  1 , Avnesh S Thakor  1
Affiliations
Review

Mesenchymal stromal cells for the treatment of Alzheimer's disease: Strategies and limitations

Shobha Regmi et al. Front Mol Neurosci. .

Abstract

Alzheimer's disease (AD) is a major cause of age-related dementia and is characterized by progressive brain damage that gradually destroys memory and the ability to learn, which ultimately leads to the decline of a patient's ability to perform daily activities. Although some of the pharmacological treatments of AD are available for symptomatic relief, they are not able to limit the progression of AD and have several side effects. Mesenchymal stem/stromal cells (MSCs) could be a potential therapeutic option for treating AD due to their immunomodulatory, anti-inflammatory, regenerative, antioxidant, anti-apoptotic, and neuroprotective effects. MSCs not only secret neuroprotective and anti-inflammatory factors to promote the survival of neurons, but they also transfer functional mitochondria and miRNAs to boost their bioenergetic profile as well as improve microglial clearance of accumulated protein aggregates. This review focuses on different clinical and preclinical studies using MSC as a therapy for treating AD, their outcomes, limitations and the strategies to potentiate their clinical translation.

Keywords: Alzheimer’s disease; mesenchymal stem cells; mesenchymal stromal cells; microglia; neurons; neuroprotection.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mechanism of protective effects of MSCs in AD. In AD, neuronal loss and synaptic dysfunction occur due to the apoptosis of neurons by accumulating different proteins such as Aβ and hyperphosphorylated tau. MSCs work in pleiotropic mechanisms in this pathology to attenuate AD via secretion of various neuroprotective and neurotrophic factors such as VEGF, GDNF, BDNF, and several miRNAs in soluble or insoluble form as EVs. As a result, MSCs help in the clearance of aggregated proteins by increasing microglial phagocytosis, reprogramming microglia into anti-inflammatory phenotype, attenuating oxidative stress and neuronal apoptosis, and promoting neurogenesis from neural progenitor cells.
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References

    1. Alavi Naini S. M., Soussi-Yanicostas N. (2015). Tau Hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies? Oxid. Med. Cell Longev. 2015:151979. 10.1155/2015/151979 - DOI - PMC - PubMed
    1. Alexanian A. R. (2005). Neural stem cells induce bone-marrow-derived mesenchymal stem cells to generate neural stem-like cells via juxtacrine and paracrine interactions. Exp. Cell Res. 310 383–391. 10.1016/j.yexcr.2005.08.015 - DOI - PubMed
    1. Alonso A. C., Grundke-Iqbal I., Iqbal K. (1996). Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat. Med. 2 783–787. 10.1038/nm0796-783 - DOI - PubMed
    1. Alzheimer’s Association (2019). 2019 Alzheimer’s disease facts and figures. Alzheimer Dement 15 321–387. 10.1016/j.jalz.2019.01.010 - DOI
    1. Baruch K., Deczkowska A., Rosenzweig N., Tsitsou-Kampeli A., Sharif A. M., Matcovitch-Natan O., et al. (2016). PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer’s disease. Nat. Med. 22:135. 10.1038/nm.4022 - DOI - PubMed

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