Objective: This study looked into the therapeutic potential of human induced pluripotent stem cell derived mesenchymal stromal cells (iMSCs) in a MPTP induced Parkinson’s disease rat model.

Background: PD is a neurodegenerative disorder marked by the selective loss of dopaminergic neurons in the SNpc, leading to motor and non-motor impairments. Current treatments mainly provide symptomatic relief but fail to halt disease progression. MSC based therapies show neuroprotective potential, but primary MSCs face donor variability and limited availability. iPSC-derived MSCs offer a scalable and ethically acceptable alternative, providing a consistent and renewable cell source with comparable differentiation capacity and immunomodulatory potential.

Method: An in vivo PD model was established by intranasal administration of MPTP in Wistar rats. Healthy iMSCs were transplanted intramuscularly at either pre motor or post motor disease stages. Behavioral outcomes were assessed through olfactory discrimination, locomotor activity, motor coordination tests and peripheral nerve conduction studies. Dopaminergic neuron survival, dopamine release and midbrain neuroinflammation were evaluated using immunohistochemistry, ELISA and flow cytometry. Biodistribution and persistence of transplanted cells were examined using near infrared (NIR) imaging.

Results: iMSC transplantation at the post motor stage significantly improved behavioural performance, including enhanced olfactory discrimination, locomotor activity, motor coordination, and peripheral nerve conduction velocity compared with MPTP treated rats. Midbrain analyses revealed reduced neuroinflammation, increased dopaminergic neurons, and elevated dopamine release. Similar effects were observed in pre-motor transplanted rats when assessed two weeks post MPTP administration however, efficacy declined at later time points. NIR imaging showed that transplanted iMSCs bypassed the first-pass effect and readily reached the midbrain, although circulating cell numbers progressively decreased over time.

Conclusion: These findings indicate that iMSC transplantation decreases MPTP induced Parkinsonian pathology by reducing neuroinflammation and promoting dopaminergic neuron survival. This study emphasizes the therapeutic promise of iMSCs as a renewable cell source for PD while highlighting the need to improve long term cell persistence to achieve sustained neuroprotective effects.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/restoring-dopaminergic-function-ipsc-derived-mscs-show-therapeutic-promise-in-parkinsons-disease-rat-model/