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// Fabin Han 1, 6, * , Chao Chen 1, * , Wei Wang 1, * , Hao Song 1 , Sen Li 1 , Jing Duan 1 , Xianjie Lu 1 , Shichao Wu 1 , Nan Zhang 1 , Qingfa Chen 1 , Yan Wang 1 , Shuwei Liu 2 , Chongluo Fu 3 , Chengbiao Lu 4 and Paul Lu 5 1 Centre for Stem Cells and Regenerative Medicine, The Institute for Tissue Engineering & Regenerative Medicine, Liaocheng University/The Liaocheng People’s Hospital, Liaocheng, Shandong, China 2 Department of Human Anatomy, Shandong University, Jinan, Shandong, China 3 College of Biological Science, Liaocheng University, Liaocheng, Shandong, China 4 Department of Neurobiology, Xinxiang Medical College, Xinxiang, Henan, China 5 Department of Neurosciences, University of California at San Diego, La Jolla, CA, USA 6 The Institute for Translational Medicine, The Second Affiliated Hospital, Shandong University, Jinan, Shandong, China * These authors have contributed equally to this work Correspondence to: Fabin Han, email: fhan2013@126.com Keywords: Parkinson's disease; dopamine neuronal differentiation; umbilical cord-derived mesenchymal stromal cell; transplantation; gerotarget Received: July 29, 2017     Accepted: January 01, 2018     Published: January 02, 2018 ABSTRACT Cell therapy have a great potential for the treatment of neurodegenerative disease, such as Parkinson's disease (PD). Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) have been reported to have multipotent differentiation ability. However, the therapeutic impact and mechanisms of dopamine neuronal differentiation from hUC-MSCs in PD are not determined. Here we developed a new protocol to induce dopamine neuron conversion from hUC-MSCs by addition of the growth cocktail containing noggin, CHIR99021, SHH, FGF8, TGFβ, GDNF, and BDNF. Then we transplanted the hUC-MSCs and the growth factor cocktail into the lesion side of the midbrain of 6-OHDA lesioned rat model of PD. The effects of hUC-MSC transplantation on the dopaminergic neuronal differentiation and motor behaviors of the rats were investigated. We found that in the presence of these molecules, the cultured hUC-MSCs showed a high efficient DA neuronal conversion in vitro . In combination with the growth cocktail, grafted hUC-MSCs also showed a highly efficient DA neuronal conversion in the midbrain of 6-OHDA lesioned rats. Both the grafted hUC-MSCs and the differentiated TH-positive neurons survived in 6-OHDA lesioned rats during the post-grafting period of 16 weeks. The hUC-MSCs-derived TH-positive neurons displayed the same electrophysiological profile as DA neurons in vivo . More importantly, rats with transplanted hUC-MSCs showed progressive improvements in motor behaviors compared to controls from weeks 4 to 16 post-grafting. These results demonstrated the efficacy and usefulness of the growth cocktail in combination with hUC-MSC transplantation in 6-OHDA lesioned rats and provided a promising cell-based treatment strategy for the PD patients.

Human umbilical cord-derived mesenchymal stromal cells ameliorated motor defects of 6-OHDA-induced rat model of Parkinson's disease