Genetically engineered BMSCs promote dopamine secretion and ameliorate motor dysfunction in a Parkinson's disease rat model.

Abstract

Regenerative therapy based on mesenchymal stem cells (MSCs) is regarded as a promising strategy for treating Parkinson's disease (PD). Previous studies have shown that mesenchymal stem cell transplantation has the potential to treat Parkinson's disease, but its specific mechanism of action is still unclear. In the present study, we generate genetically engineered bone marrow mesenchymal stem cells (BMSCs) encoding three critical genes (TH, DDC, and GCH1) for dopamine synthesis (DA-BMSCs). The DA-BMSCs maintain their MSCs characteristics and stable ability to secrete dopamine after passage. Moreover, the DA-BMSCs survived and functioned in a rat model of PD treated with 6-OHDA 8 weeks after transplantation. Histological studies showed that DA-BMSCs could differentiate into various functional neurons and astrocytes, and DA-BMSCs derived mature dopaminergic neurons extended dense neurites into the host striatum. Importantly, DA-BMSCs promoted the reconstruction of midbrain dopamine pathways by upregulating striatal dopamine and 5-HT levels and downregulating the levels of inflammatory factors including IL-6, TNF-α, and IL-10. These findings suggest that engineered mesenchymal stem cell transplantation for dopamine synthesis may be an attractive donor material for treating Parkinson's disease.