The Study Of Notch Signal Pathway During Trans-differentiation Of Hbmscs To Doparminergic Neurons Mediated By Lmx1? And NTN (Induction Differentiation Of HBMSCs And Construction Of Parkinson-like Model)

Objective: To investigate the differentiation of h BMSCs(Human marrow mesenchymal stem cells,h BMSCs)into dopaergic neuron-like cells and as a neurotrophic factor gene NTN(Neuturin,NTN)and transcription factor gene Lmx1a(LIM homeobox transcription factor 1-alpha,Lmx1? Transplantation of a vector for the treatment of rotenone-Parkinson-like mice.Methods: In this study,we infect the h BMSCs with a recombinant lentiviral veer carried NTN gene and the transcription factor Lmx1? gene,and induced differentiation of h BMSCs into dopaminergic neuron-like cells by chemical factors,cytokines,organically combinates with transgenic method.In vivo activity assays of induced cells were performed in rotenone PD mouse model with was established in our previous work.The induced cells were transplanted into the substantia nigra region of the model by stereotactic injection.Then,the growth and development of dopaminergic neuron-like cells in the model were comprehensively evaluated.By pathological deletion of neuron-specific mar hems such as midbrain dopamine.Results:(1)Recombinant lentivirus carrying NTN and Lmx1 a gene was successfully constructed.(2)h BMSCs were successfully differentiated into dopaminergic neuron-like cel s.(3)Rotenone Parkinson-like mouse mode was successfully constructed.Conclusion: Recombinant lentivirus-mediated NTN and Lmx1 a are introduced into h BMSCs and successfully differentiate into mature neuron-like cells,expressing specific proteins in combination with chemical a nd biological levels.The rotenone and chronic stress exacerbated the degeneration and death of DA neurons in the substantia nigra of mice,and the neurotransmitter homeostasis was destroyed,which eventually aggravated the PD-like expression of mice;its pathogenesis is more similar with the pathogenesis of human PD.