The potential use of mesenchymal stem cells and their exosomes in Parkinson's disease treatment

Abstract

Parkinson's disease (PD) is the second most predominant neurodegenerative disease worldwide. It is recognized clinically by severe complications in motor function caused by progressive degeneration of dopaminergic neurons (DAn) and dopamine depletion. As the current standard of treatment is focused on alleviating symptoms through Levodopa, developing neuroprotective techniques is critical for adopting a more pathology-oriented therapeutic approach. Regenerative cell therapy has provided us with an unrivalled platform for evaluating potentially effective novel methods for treating neurodegenerative illnesses over the last two decades. Mesenchymal stem cells (MSCs) are most promising, as they can differentiate into dopaminergic neurons and produce neurotrophic substances. The precise process by which stem cells repair neuronal injury is unknown, and MSC-derived exosomes are suggested to be responsible for a significant portion of such effects. The present review discusses the application of mesenchymal stem cells and MSC-derived exosomes in PD treatment.

Keywords: Exosome; Mesenchymal stem cell; Parkinson's disease; Therapeutic application.

Fig. 1

(1) Exosomes are separated from cell culture and bodily fluids using a variety of techniques. (2) They contain a series of Rab proteins, tetraspanins, heat shock proteins, intercellular adhesion molecule (ICAM-1), endosome-associated proteins (TSG101), and nucleic acids such as mRNAs and mRNAs, according to fluorescence-activated cell sorting (FACS), mass spectrometry analyses, and Western blot

Fig. 2

(1) Secretion of α-syn can occur via secretory lysosomes (exocytosis), microvesicle shedding, or multivesicular bodies, with the second and third methods including the release of α-syn into exosomes. α-Syn can be eliminated from the extracellular space by proteolysis. One of the tiny molecules implicated in the proteolytic degradation of aggregated α-syn would be MMP2, a factor generated from MSCs. MMP-2 produced from MSCs breaks freshly formed amyloid fibrils, resulting in a considerable decrease in the quantities of insoluble and oligomeric α-syn. (2) Furthermore, tiny compounds generated from MSCs alter PI3K/Akt signaling, which ultimately regulates multiple downstream targets to increase autophagy. Upregulation of PI3K/AKT promotes autophagy via regulating the expression of autophagy-related genes such as BECN1, ATG, and GABARAPL1. As a result, autophagic flux upregulation by MSC derived small molecules increases the clearance of harmful α-syn aggregates and so plays a vital role in maintaining α-syn homeostasis in the PD-related milieu. (3) MSC interactions with immune system cells, with primary signaling pathways revealed. (4) MSCs secrete neurotrophic factors like as BDNF, NGF, and FGF-2, which interact with injured axons and cause axonal regrowth. 5) When activated by pro-inflammatory mediators, MSCs release paracrine factors such as TSG-6 and IL-4. Paracrine factors stimulate M2 macrophage polarization, resulting in an elevated Th2 response