Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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

Fabin Han _, Chao Chen, Wei Wang, Hao Song, Sen Li, Jing Duan, Xianjie Lu, Shichao Wu, Nan Zhang, Qingfa Chen, Yan Wang, Shuwei Liu, Chongluo Fu, Chengbiao Lu and Paul Lu

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Abstract

Fabin Han1,6,*, Chao Chen1,*, Wei Wang1,*, Hao Song1, Sen Li1, Jing Duan1, Xianjie Lu1, Shichao Wu1, Nan Zhang1, Qingfa Chen1, Yan Wang1, Shuwei Liu2, Chongluo Fu3, Chengbiao Lu4 and Paul Lu5

1Centre for Stem Cells and Regenerative Medicine, The Institute for Tissue Engineering & Regenerative Medicine, Liaocheng University/The Liaocheng People’s Hospital, Liaocheng, Shandong, China

2Department of Human Anatomy, Shandong University, Jinan, Shandong, China

3College of Biological Science, Liaocheng University, Liaocheng, Shandong, China

4Department of Neurobiology, Xinxiang Medical College, Xinxiang, Henan, China

5Department of Neurosciences, University of California at San Diego, La Jolla, CA, USA

6The 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.


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