Neuropsychiatric Disease and Treatment (Jan 2020)
Intranasal Delivery of Bone Marrow Stromal Cells Preconditioned with Fasudil to Treat a Mouse Model of Parkinson’s Disease
Abstract
Yilin Tang,1,* Linlin Han,1,* Xiaochen Bai,1,2 Xiaoniu Liang,1 Jue Zhao,1 Fang Huang,2 Jian Wang1 1Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2The State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian WangDepartment of Neurology and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaTel +86-133 2193 4789Fax +86-21-5288 8163Email [email protected]: Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil.Methods: A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed.Results: Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone.Conclusion: The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.Keywords: Parkinson’s disease, intranasal delivery, bone marrow stromal cells, fasudil
