Investigating Stem Cells and Exosomes as Emerging Therapies for Parkinson’s Disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to bradykinesia, tremor, rigidity, and postural instability. Current pharmacological treatments provide symptomatic relief but do not address the underlying neurodegeneration. Novel regenerative strategies—particularly stem cell and exosome-based therapies—are now being actively explored for disease-modifying potential.

Stem Cell-Based Therapies in Parkinson’s Disease

Stem cell transplantation aims to replace the lost dopaminergic neurons and reestablish dopaminergic signaling in the striatum. Several clinical trials have demonstrated early promise, particularly with the use of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs).

1. Induced Pluripotent Stem Cells (iPSCs)

In a Phase I trial conducted by Mass General Brigham, autologous iPSCs were derived from patients’ own blood cells, differentiated into dopaminergic neurons, and transplanted into the brain. The study confirmed the safety and feasibilityof the procedure, with long-term follow-up ongoing to evaluate clinical efficacy.

2. Embryonic Stem Cell–Derived Neurons

Memorial Sloan Kettering Cancer Center initiated a clinical trial involving human embryonic stem cell–derived dopaminergic progenitors. In 12 patients with PD, the transplanted neurons survived, integrated, and began forming connections within the brain. Early patient-reported improvements in motor symptoms were observed, though larger trials are needed to confirm efficacy.

3. Bemdaneprocel (BlueRock Therapeutics)

Bemdaneprocel is an investigational therapy involving the transplantation of pluripotent stem cell–derived dopaminergic neurons. In a recent Phase I trial, the treatment was well tolerated and resulted in improved motor scores over 12 months. A Phase III trial is currently in planning, indicating growing confidence in this approach.

Exosome-Based Approaches

Exosomes are nano-sized extracellular vesicles that transport proteins, lipids, and nucleic acids between cells. Their ability to cross the blood-brain barrier and mediate intercellular communication has sparked interest in their therapeutic application for PD.

1. MSC-Derived Exosomes

Mesenchymal stem cell–derived exosomes (MSC-Exos) have been shown to:

• Inhibit apoptosis of dopaminergic neurons

• Modulate neuroinflammation

• Promote neurogenesis in PD animal models

A study published in Cell Death & Disease demonstrated that exosomes derived from umbilical cord MSCs localized to the substantia nigra and reduced neuronal loss in rodent models of Parkinson’s.

2. Dental Pulp Stem Cell Exosomes

A study from Stem Cell Research & Therapy highlighted the neuroprotective effects of exosomes derived from dental pulp stem cells, which prevented dopaminergic neuron loss in in vitro PD models. This adds to the growing body of evidence supporting exosomes as cell-free therapeutic candidates.

3. Exosomes as Drug Delivery Vehicles

Due to their endogenous targeting capability and stability in circulation, exosomes are also being investigated as delivery vehicles for small molecules, mRNA, or siRNA directed at neurodegenerative processes in Parkinson’s disease.

Conclusion

While both stem cell transplantation and exosome-based therapy remain investigational, they represent highly promising avenues for disease modification in Parkinson’s disease. Stem cells offer the potential for cell replacement, whereas exosomes may provide neuroprotection and targeted drug delivery. Continued research and clinical trials will be crucial in translating these experimental approaches into standard clinical practice.

Sources

1. Mass General Brigham. Clinical Trial of Novel Stem Cell Treatment for Parkinson’s Disease.

   https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/clinical-trial-novel-stem-cell-treatment-for-parkinsons

2. Memorial Sloan Kettering Cancer Center. Investigational Cell Therapy Shows Early Promise.

   https://www.mskcc.org/news/potential-treatment-for-parkinsons-using-investigational-cell-therapy-shows-early-promise

3. UCI Health. BlueRock’s Parkinson’s Study Published in Nature.

   https://www.ucihealth.org/about-us/news/2025/04/parkinsons-study-nature

4. Xie C, et al. Exosomes Derived from Human Umbilical Cord MSCs Protect Dopaminergic Neurons in PD Models. Cell Death & Disease (2020).

   https://www.nature.com/articles/s41419-020-2473-5

5. Farid N, et al. Dental Pulp Stem Cell–Derived Exosomes for Parkinson’s Disease. Stem Cell Res Ther (2022).

   https://stemcellres.biomedcentral.com/articles/10.1186/s13287-022-03050-4

6. Samani T, et al. Exosomes as Emerging Therapeutics in Neurodegeneration. Neuroscience & Biobehavioral Reviews (2023).

   https://www.sciencedirect.com/science/article/pii/S0306452223004098