Adipose tissue‐derived stem cells as a potential candidate in treatment of Alzheimer's disease: A systematic review on preclinical studies

Abstract

In recent years, numerous investigations have evaluated the efficacy of adipose tissue‐derived stem cells (ADSCs) and their exosome transplantation in managing Alzheimer's disease (AD) in different animal models. However, there are still many contradictions among the studies that hinder reaching a reliable conclusion. Therefore, we aimed to systematically review the existing evidence regarding the efficacy of ADSCs administration in treatment of AD. The systematic search was conducted in the databases of Medline (via PubMed), Embase, Scopus, and Web of Science, in addition to the manual search in Google and Google scholar, to find articles published until March 13, 2021. Preclinical studies were included and two independent reviewers summarized the eligible papers. Ten articles were included in our review. The treatment strategies varied between isolated ADSC, ADSCs exosomes, ADSCs conditioned medium, and combination therapy (ADSCs plus conditioned medium in one study, and ADSCs plus melatonin in another study). Overview of the included articles showed promising results of ADSCs and its conditioned medium/exosome administration in animal models of AD. These studies showed significant learning and memory improvements through ADSCs and their conditioned medium/exosome administration in animal models of AD. In addition, the application of ADSCs reduced the amyloid‐beta plaque deposits in the hippocampus and neocortex of these animals. Based on the aforementioned evidence, studies have suggested potential beneficial effects of ADSCs in the treatment of AD, particularly through decreasing the size of Aβ plaques and improvement of cognitive deficits. Further investigations regarding the subject are encouraged to achieve more accurate conclusions.

Neuro-Adipokine Crosstalk in Alzheimer’s Disease

“…The pro-inflammatory ADSCs can increase neuroinflammation by inducing proliferation and differentiation of CD4+ and CD8+ T cells [ 17 ]. Transplantation of ADSCs into a rat model of AD ameliorates cognitive impairments, enhances Aβ clearance, and suppresses apoptosis and neuroinflammation by modulating central and systemic SIRT1 levels [ 18 , 19 ]. Intraventricular injection of ADSCs has been shown to improve AD pathogenesis by modulating central cholesterol homeostasis [ 20 ].…”

Adipose tissue‐derived mesenchymal stem cells ameliorate cognitive impairment in Alzheimer's disease rat model: Emerging role of SIRT1

“…[33][34][35] A growing body of evidence has shown that Ad-MSCs exhibit potential beneficial impact in the rescue of AD, particularly through reducing the size of Aβ plaques and mitigation of cognitive decline. 36 In fact, Ad-MSCs have been reported to mediate their actions through various mechanisms, including their immunomodulatory abilities, tissue regenerative capacity, and most importantly via the secretion of various cytokines, growth factors, and extracellular vesicles which employ various bioactive mediators, immunomodulatory, and anti-inflammatory molecules. 22,[37][38][39][40] Yet, further research is warranted to fully elucidate the molecular factors that mediate their various therapeutic beneficial effects in the context of different diseases.…”

“…Notably, there has been a surge in the use of Ad‐MSCs in the treatment of different neurodegenerative disorders 33–35 . A growing body of evidence has shown that Ad‐MSCs exhibit potential beneficial impact in the rescue of AD, particularly through reducing the size of Aβ plaques and mitigation of cognitive decline 36 . In fact, Ad‐MSCs have been reported to mediate their actions through various mechanisms, including their immunomodulatory abilities, tissue regenerative capacity, and most importantly via the secretion of various cytokines, growth factors, and extracellular vesicles which employ various bioactive mediators, immunomodulatory, and anti‐inflammatory molecules 22,37–40 .…”