An update on stem cell and stem cell-derived extracellular vesicle-based therapy in the management of Alzheimer's disease

Abstract

Globally, neurological diseases pose a major burden to healthcare professionals in terms of the management and prevention of the disorder. Among neurological diseases, Alzheimer's disease (AD) accounts for 50%-70% of dementia and is the fifth leading cause of mortality worldwide. AD is a progressive, degenerative neurological disease, with the loss of neurons and synapses in the cerebral cortex and subcortical regions. The management of AD remains a debate among physicians as no standard and specific "disease-modifying" modality is available. The concept of 'Regenerative Medicine' is aimed at regenerating the degenerated neural tissues to reverse the pathology in AD. Genetically modified engineered stem cells modify the course of AD after transplantation into the brain. Extracellular vesicles (EVs) are an emerging new approach in cell communication that involves the transfer of cellular materials from parental cells to recipient cells, resulting in changes at the molecular and signaling levels in the recipient cells. EVs are a type of vesicle that can be transported between cells. Many have proposed that EVs produced from mesenchymal stem cells (MSCs) may have therapeutic promise in the treatment of AD. The biology of AD, as well as the potential applications of stem cells and their derived EVs-based therapy, were explored in this paper.

Keywords: Alzheimer’s disease; Cellular therapy; Clinical trial; Extracellular vesicles; Mesenchymal stem cell.

Fig. 1

Neurogenic signaling of adult stem cells mediated through growth factors, neurotrophic factors, and neurotransmitters as shown in circles. The pathways involved in their signaling and their mediation of action through epigenetic regulation and transcriptional factors involved are given in boxes. Created with BioRender.com

Fig. 2

Actions of MSC-EVs in AD. Created with BioRender.com