Human dental pulp stem cell-derived mitochondria restore mitochondrial function and promote neuroregeneration in a cellular model of Parkinson's disease.

BACKGROUND

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons, primarily due to mitochondrial dysfunction. Current treatments focus on managing symptoms but are unable to regenerate neurons. Human dental pulp stem cells (hDPSCs) offer a promising source for neurodegenerative therapy due to their accessibility and neuro-supportive properties. However, research on the mitochondrial characteristics of hDPSCs and their therapeutic potential remains limited. This study investigates the capacity of mitochondria isolated from hDPSCs to restore mitochondrial function and promote neuronal recovery and function in a PD cellular model.

METHODS

hDPSCs were isolated and characterized for mesenchymal stem cell properties. Mitochondria were isolated, quantified, and assessed for viability and morphology using MitoTracker staining and transmission electron microscopy. Mitochondrial uptake and functional recovery were evaluated in a PD cellular model using MPP⁺-treated differentiated SH-SY5Y cells. Mitochondrial function was assessed by measuring Complex I activity, ATP production, and reactive oxygen species (ROS) levels. Neuroregeneration and synaptic function were analyzed through neurite length, growth-associated protein 43 (GAP43) and tyrosine hydroxylase (TH), Synaptophysin (SYP), dopamine transporter (DAT), calcium imaging, and mitochondrial dynamics.

RESULTS

Isolated hDPSC-derived mitochondria were mostly viable, spherical, and displayed immature cristae. In MPP⁺-treated SH-SY5Y cells, mitochondrial transfer restored Complex I activity, elevated ATP production, and reduced ROS. Treated cells also showed significantly longer neurites and increased expression of GAP43, TH, SYP, and DAT. Calcium imaging revealed restored intracellular calcium responses upon stimulation. Mitochondria from hDPSCs localized in both cell bodies and neurites and remained distinct from damaged host mitochondria, supporting synaptic function.

CONCLUSIONS

Mitochondria derived from hDPSCs can restore bioenergetic function, reduce oxidative stress, and promote structural and functional recovery in a PD cellular model. These findings highlight the foundational therapeutic potential of hDPSC-derived mitochondria as a regenerative approach for neurodegenerative diseases.

© 2025. The Author(s).