Abstract
Alzheimer’s disease (AD), as a neurodegenerative disorder, is characterized by mass neuronal and synaptic loss and, currently, there are no successful curative therapies. Extracellular vesicles (EVs) are an emerging approach to intercellular communication via transferring cellular materials such as proteins, lipids, mRNAs, and miRNAs from parental cells to recipient cells, leading to the reprogramming of the molecular machinery. Numerous studies have suggested the therapeutic potential of EVs derived from mesenchymal stem cells (MSCs) in the treatment of AD, based on the neuroprotective, regenerative and immunomodulatory effects as effective as MSCs. In this review, we focus on the biology and function of EVs, the potential of MSC-derived EVs for AD therapy in preclinical and clinical studies, as well as the potent mechanisms of MSC-derived EVs actions. Finally, we highlight the modification strategies and diagnosis utilities in order to make advance in this field.
Highlights
Alzheimer’s disease (AD) is the world’s most common cause of dementia that will affect over 100 million people by 2050, and which will bring a significant physical, psychological, social and economic burden to patients, their families, caregivers and society [1]
Increasing evidence suggests that AD pathogenesis is closely associated with the neuroinflammation, which might occur at early stage or mild cognitive impairment (MCI) even before Aβ plaque formation [105,106]
In line with other findings, our study showed that mesenchymal stem cells (MSCs)-derived Extracellular vesicles (EVs) inhibited astrocytes and microglia activation in the brain of AD mice, indicating that these effects are attributed to immunomodulatory properties of EVs [70,71,81]
Summary
Alzheimer’s disease (AD) is the world’s most common cause of dementia that will affect over 100 million people by 2050, and which will bring a significant physical, psychological, social and economic burden to patients, their families, caregivers and society [1]. Studies have indicated that MSCs are able to reduce Aβ deposition, enhance neurogenesis, alleviate spatial learning and memory deficits in both cellular models and animal models of AD [22,23,24] These therapeutic effects in tissue protection and repair are attributed to the paracrine action of MSCs, and further emphasize the role of soluble factors including extracellular vesicles (EVs) secreted from MSCs [25,26]. EVs can be divided into three classes depending on their size and origins, including exosomes, microvesicles (MVs) and apoptotic bodies (ABs) [33]. The term “EV” is widely used in research and the use of other terms should be defined carefully and clearly
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