Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

Abstract

Extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer's disease (AD). Studies have shown that aggregates of extracellular Aβ can induce neuroinflammation mediated neurotoxic signaling through microglial activation and release of pro-inflammatory factors. Thus, modulation of Aβ might be a potential therapeutic strategy for modifying disease progression. Recently, a large number of reports have confirmed the beneficial effects of mesenchymal stem cells (MSCs) on AD. It is believed to reduce neuroinflammation, reduce Aβ amyloid deposits and NFTs, increase acetylcholine levels, promote neurogenesis, reduce neuronal damage, and improve working memory and cognition. In this review, we focus on the role of MSCs in clearing Aβ deposition. MSCs have the potential to modulate Aβ-related microenvironments via enhancement of autophagy, proteolysis of Aβ aggregates, phagocytic clearance of Aβ by microglial M2 polarization, decrease oxidative stress (OS), and correction of abnormal sphingolipid (SL) metabolism. With advantages in clinical applications, these data suggest that the use of MSCs as a multi-target modulator of Aβ would be an effective therapeutic approach in AD.

The effect of different sources of mesenchymal stem cells on microglia states

“…It has been suggested that the prolonged presence of microglial reaction after TBI increases the chance of Alzheimer’s disease ( Ramos-Cejudo et al, 2018 ). In studies of Alzheimer’s disease models, transplanted MSCs were found to promote the conversion of microglia from the CD86 + to the Arg-1 + state through paracrine effects ( Campos et al, 2022 ; Zhang R. et al, 2022 ). MSCs regulate microglial states by secreting the paracrine factors Galectin-1 (Gal-1) ( Seo et al, 2022 ), tumor necrosis factor-alpha-induced gene/protein 6 (TSG-6) ( Liu et al, 2019 ; Nam et al, 2020 ), and IL-13 ( Taj et al, 2018 ), etc.…”

Exploring the vital role of microglial membrane receptors in Alzheimer’s disease pathogenesis: a comprehensive review

“…The main pathological features associated with AD are extracellular amyloid-β plaques (Aβ), hyperphosphorylation of tau protein, neurofibrillary tangles (NFTs), neuron death, and synaptic loss in the hippocampus, cortex, and amygdala [4,5]. Aβ plays a critical pathogenic role in AD, all types of AD are characterized by the accumulation of Aβ, which triggers a series of neuroinflammations, culminating in neuronal dysfunction and death [6].…”