Overexpression of Lmx1a/NeuroD1 Mediates the Differentiation of Pulmonary Mesenchymal Stem Cells into Dopaminergic Neurons and Repairs Motor Dysfunction in Parkinson’s Disease Rats

Background: Mesenchymal stem cells (MSCs) have shown great potential in treating neurodegenerative diseases, including Parkinson’s disease (PD), due to their ability to differentiate into neurons and secrete neurotrophic factors. Genetic modification of MSCs for PD treatment has become a research focus. Methods: In this study, rat pulmonary mesenchymal stem cells (PMSCs) were transduced with lentiviral vectors carrying Lmx1a/NeuroD1 to establish genetically engineered PMSCs (LN-PMSCs) and induce their differentiation into dopaminergic neurons. The LN-PMSCs were then transplanted into the right medial forebrain bundle region of PD model rats prepared using the 6-Hydroxydopamine (6-OHDA) method. Four weeks post-transplantation, the survival and differentiation of the cells in the brain and motor function of the PD rats were evaluated. Results: The results showed that after 12 days of induction, the genetically modified LN-PMSCs had differentiated into a large number of dopaminergic neurons. Four weeks post-transplantation, these cells significantly improved motor dysfunction in PD rats and promoted the expression of neuron marker TUJ1, dopaminergic neuron markers FOXA2 and TH, gamma-aminobutyric acid-ergic (GABAergic) neuron marker GABA, astrocyte marker GFAP, presynaptic marker SYN, and postsynaptic marker PSD95 in the transplantation area. Conclusion: Our findings suggest that the gene-engineered PMSCs cell line overexpressing Lmx1a and NeuroD1 (LN-PMSCs) transplantation could be a potential therapeutic strategy for treating PD.