Cite this article as: Al Darmaki A A, Malahifci R, Ahmed S, et al. (March 14, 2026) Mesenchymal Stem Cell Therapy in Parkinson’s Disease: A Comprehensive Review. Cureus 18(3): e105206. doi:10.7759/cureus.105206 

Abstract

Parkinson’s disease (PD) is a gradual neurodegenerative condition characterized by dopaminergic neuron death, α-synuclein pathology, neuroinflammation, oxidative stress, and mitochondrial dysfunction. Current treatments (levodopa, deep brain stimulation (DBS), etc.) are mainly symptomatic and have limited effect on slowing disease progression. Mesenchymal stem/stromal cells (MSCs) are emerging candidates for a disease-modifying approach because they can modulate both the adaptive and innate immune responses, secreting neurotrophic and pro-angiogenic factors, affecting glial phenotype, and delivering extracellular vesicles/exosomes, which may lessen neuroinflammation and/or proteotoxic stress. Early-phase clinical research (phase 1 dose escalation of intravenous (IV) allogeneic bone marrow (BM)-derived MSCs; recent phase 2 randomized placebo-controlled IV allogeneic MSC trials) indicates that MSCs may be feasible and safe in the short term, although these have demonstrated some symptomatic benefits in motor outcomes. However, notable variability exists across dosing regimens, and significant placebo effects were observed. In this review, we summarize the sources of MSCs, relevant mechanisms of MSC activity in PD biology (including preclinical evidence), clinical trial results, safety issues, routes of administration, and challenges (including potency assays, batch variation, endpoint selection, durability, and regulatory/ethical limitations). We conclude that MSC-based interventions in PD remain investigational, and future clinical trials should focus on standardizing manufacturing processes, utilizing robust potency metrics, incorporating biomarker-rich designs, and selecting clinically meaningful endpoints.

Conclusions

PD has seen progress transitioning from preclinical studies demonstrating promise toward early phase (i.e., traditional phase 1) clinical trials of human IV allogeneic BM-MSCs. Many IV allogeneic BM-MSC therapies have shown feasibility and short-term tolerability and have given initial signals of improvement in motor function in a controlled research environment. Despite these factors, the heterogeneity of the products used, the strong placebo effect, and the lack of full understanding of the mechanism of action have made it extremely difficult to draw definitive conclusions at this time. MSC-based therapies/interventions are considered investigational, and further progress will require established standards of manufacture, properly conducted potency testing, and rigidly enforced blinding and control protocols, as well as biologically informative biomarkers of therapy, to distinguish the symptomatic effects of therapy from disease-modifying effects.

• Abstract
• Introduction & Background
• Review
• Conclusions
• References