Abstract
// 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.
Highlights
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, affecting 1% of the population aged 60 years and older and 3-5% of the population above the age of 85 [1,2,3]
We examined if the 6-OHDA induced PD rats are depleted of the dopamine neurons and found that rats showed a dramatic loss of TH-positive neuronal fibers in substantia nigra (SN) of the lesion side compared to the intact side of the rats as previous reports four weeks after an unilateral intrastriatal injection of 6-OHDA [24, 36]
The growth cocktail used in this study efficiently induced neuronal differentiation and DA neuronal conversion from hUCMSCs
Summary
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, affecting 1% of the population aged 60 years and older and 3-5% of the population above the age of 85 [1,2,3]. Experimental studies on rodent and non-human primate models for PD in the 1970s and 1980s showed that fetal brain-derived DA neurons could survive, re-innervate the striatum and release DA after grafted [10,11,12,13,14]. The induced pluripotent stem (iPS) cells generated from accessible somatic cells have provided an unprecedented novel autologous source for human DA neuron grafts [22,23,24] The functionality of these in vitro generated human DA neurons after intrastriatal implantation have been recently studied in rodent and non-human primate models for PD. The mesenchymal stem cells account for a small fraction of mesenchymal stromal cells with stem cell activity [28,29,30]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
