Mesenchymal stem cells and their secretome: a promising approach for Parkinson’s disease treatment

Abstract Parkinson’s disease (PD) is a progressive and incapacitating neurodegenerative disorder that affects millions worldwide, with a steadily increasing prevalence. PD is characterized by Lewy body aggregation and dopaminergic neuron degeneration, leading to significant motor and non-motor impairments that severely compromise patients’ quality of life. The growing incidence of PD has created a substantial burden on patients, families, and society. Current treatments, such as Levodopa, only alleviate symptoms without halting disease progression, highlighting the critical needs for therapies that cannot only relieve symptoms but also, reverse clinical conditions. In recent years, Mesenchymal stem cells (MSCs) have emerged as promising candidates due to their ability to differentiate into dopaminergic neurons and secrete neurotrophic factors. This therapy demonstrates notable characteristics including, neuroprotective effects, remyelination promotion, neural inflammation attenuation, and functional recovery facilitation after injury. However, MSC therapeutic benefits are primarily mediated through paracrine activity, specifically via extracellular vesicles (EVs) and exosomes. Although the precise mechanisms underlying these effects remain unclear, MSC-derived exosomes are believed to play a major role in mediating the reparative effects. EVs encapsulate various biologically active components, making them promising strategies for both therapeutic and diagnostic applications. Their ability to cross the blood–brain barrier readily represents a key advantage, while avoiding ethical concerns associated with cell-based therapies. Furthermore, bioengineering approaches can enhance their drug delivery capacity and target specificity. This review explore current insights into MSC and MSC-secretome/EV applications in PD treatment and identifies future research directions.