Abstract
Parkinson’s disease (PD) is a common neurodegenerative condition causing significant disability and thus negatively impacting quality of life. The recent advent of stem cell-based therapy has heralded the prospect of a potential restorative treatment option for PD. In particular, mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. Furthermore, hepatocyte growth factor (HGF), which shows mitogenic and morphogenetic activities in a variety of cells, including MSC, and may be implicated in the pathophysiology of PD. As such, HGF may represent a new therapeutic target for the disease. In this study, we successfully isolated and facilitated the transduction of an adenoviral vector expressing HGF (Ad-HGF) into isolated hUC-MSCs. Following transduction, the hUC-MSCs can differentiate into dopaminergic neuron-like cells secreting dopamine, tyrosine hydroxylase, and dopamine transporter. Our data suggest that hUC-MSCs have the ability to differentiate into dopaminergic neurons after transduction with Ad-HGF, providing encouraging evidence to further explore this approach to the treatment of PD.
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Abbreviations
- PD:
-
Parkinson’s disease
- hUC-MSCs:
-
Mesenchymal stem cells derived from human umbilical cord
- HGF:
-
Hepatocyte growth factor
- TH:
-
Tyrosine hydroxylase
- DAT:
-
Dopamine transporter
- DA:
-
Dopamine
References
Pluck GC, Brown RG (2002) Apathy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73(6):636–642
Bjorklund A, Kordower JH (2013) Cell therapy for Parkinson’s disease: what next? Mov Disord 28(1):110–115. doi:10.1002/mds.25343
Sharma R, McMillan CR, Niles LP (2007) Neural stem cell transplantation and melatonin treatment in a 6-hydroxydopamine model of Parkinson’s disease. J Pineal Res 43(3):245–254
Ali SF, Binienda ZK, Imam SZ (2011) Molecular aspects of dopaminergic neurodegeneration: gene–environment interaction in parkin dysfunction. Int J Environ Res Public Health 8(12):4702–4713. doi:10.3390/ijerph8124702
Wickremaratchi MM, Ben-Shlomo Y, Morris HR (2009) The effect of onset age on the clinical features of Parkinson’s disease. Eur J Neurol 16(4):450–456. doi:10.1111/j.1468-1331.2008.02514.x
Pedrosa DJ, Timmermann L (2013) Review: management of Parkinson’s disease. Neuropsychiatr Dis Treat 9:321–340. doi:10.2147/NDT.S32302
Can A, Balci D (2011) Isolation, culture, and characterization of human umbilical cord stroma-derived mesenchymal stem cells. Methods Mol Biol 698:51–62. doi:10.1007/978-1-60761-999-4_5
Michalopoulos GK, Zarnegav R (1992) Hepatocyte growth factor. Hepatology 15(1):149–155
Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA (1991) Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251(4995):802–804
Salehi Z, Rajaei F (2010) Expression of hepatocyte growth factor in the serum and cerebrospinal fluid of patients with Parkinson’s disease. J Clin Neurosci 17(12):1553–1556. doi:10.1016/j.jocn.2010.04.034
Funakoshi H, Nakamura T (2001) Identification of HGF-like protein as a novel neurotrophic factor for avian dorsal root ganglion sensory neurons. Biochem Biophys Res Commun 283(3):606–612
Hu ZX, Geng JM, Liang DM, Luo M, Li ML (2010) Hepatocyte growth factor protects human embryonic stem cell derived-neural progenitors from hydrogen peroxide-induced apoptosis. Eur J Pharmacol 645(1–3):23–31. doi:10.1016/j.ejphar.2010.07.011
Powell EM, Mars WM, Levitt P (2001) Hepatocyte growth factor/scatter factor is a motogen for interneurons migrating from the ventral to dorsal telencephalon. Neuron 30(1):79–89
Hashimoto N, Yamanaka H, Fukuoka T, Dai Y, Obata K, Mashimo T, Noguchi K (2001) Expression of HGF and c-Met in the peripheral nervous system of adult rats following sciatic nerve injury. NeuroReport 12(7):1403–1407
Halfon S, Abramov N, Grinblat B, Ginis I (2011) Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev 20(1):53–66. doi:10.1089/scd.2010.0040
Bae S, Shim SH, Park CW, Son HK, Lee HJ, Son JY, Jeon C, Kim H (2011) Combined omics analysis identifies transmembrane 4 L6 family member 1 as a surface protein marker specific to human mesenchymal stem cells. Stem Cells Dev 20(2):197–203. doi:10.1089/scd.2010.0127
Philippova M, Suter Y, Toggweiler S, Schoenenberger AW, Joshi MB, Kyriakakis E, Erne P, Resink TJ (2011) T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis. Eur Heart J 32(6):760–771. doi:10.1093/eurheartj/ehq206
Gaiba S, França LP, França JP, Ferreira LM (2012) Characterization of human adipose-derived stem cells. Acta Cir Bras 27(7):471–476
Duan HF, Wu CT, Wu DL, Lu Y, Liu HJ, Ha XQ, Zhang QW, Wang H, Jia XX, Wang LS (2003) Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor. Mol Ther 8(3):467–474
Toovey S, Jick SS, Meier CR (2011) Parkinson’s disease or Parkinson symptoms following seasonal influenza. Influenza Other Respir Viruses 5(5):328–333. doi:10.1111/j.1750-2659.2011.00232.x
Fox SH, Chuang R, Brotchie JM (2008) Parkinson’s disease-opportunities for novel therapeutics to reduce the problems of levodopa therapy. Prog Brain Res 172:479–494. doi:10.1016/S0079-6123(08)00923-0
Rascol O, Lozano A, Stern M, Poewe W (2011) Milestones in Parkinson’s disease therapeutics. Mov Disord 26(6):1072–1082. doi:10.1002/mds.23714
Flici H, Giangrande A (2012) Stem cell aging and plasticity in the Drosophila nervous system. Fly (Austin) 6(2):108–112. doi:10.4161/fly.19797
Phinney DG, Isakova I (2005) Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 11(10):1255–1265
Zhou C, Yang B, Tian Y, Jiao H, Zheng W, Wang J, Guan F (2011) Immunomodulatory effect of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells on lymphocytes. Cell Immunol 272(1):33–38. doi:10.1016/j.cellimm.2011.09.010
Kim S, Jeon BS, Heo C, Im PS, Ahn TB, Seo JH, Kim HS, Park CH, Choi SH, Cho SH, Lee WJ, Suh YH (2004) Alpha-synuclein induces apoptosis by altered expression in human peripheral lymphocyte in Parkinson’s disease. FASEB J 18(13):1615–1617
Fiszer U (2001) Does Parkinson’s disease have an immunological basis? The evidence and its therapeutic implications. BioDrugs 15(6):351–355
Lan F, Xu J, Zhang X, Wong VW, Li X, Lu A, Lu W, Shen L, Li L (2008) Hepatocyte growth factor promotes proliferation and migration in immortalized progenitor cells. NeuroReport 19(7):765–769. doi:10.1097/WNR.0b013e3282fdf69e
Koike H, Ishida A, Shimamura M, Mizuno S, Nakamura T, Ogihara T, Kaneda Y, Morishita R (2006) Prevention of onset of Parkinson’s disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson’s disease. Gene Ther 13(23):1639–1644
Kastner A, Hirsch EC, Agid Y, Javoy-Agid F (1993) Tyrosine hydroxylase protein and messenger RNA in the dopaminergic nigral neurons of patients with Parkinson’s disease. Brain Res 606(2):341–345
Corbitt J, Hagerty T, Fernandez E, Morgan WW, Strong R (2002) Transcriptional and post-transcriptional regulation of tyrosine hydroxylase messenger RNA in PC12 cells during persistent stimulation by VIP and PACAP38: differential regulation by protein kinase A and protein kinase C-dependent pathways. Neuropeptides 36(1):34–45
Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease: pathophysiologic and clinical implications. N Engl J Med 318(14):876–880
Harrington KA, Augood SJ, Kingsbury AE, Foster OJ, Emson PC (1996) Dopamine transporter (Dat) and synaptic vesicle amine transporter (VMAT2) gene expression in the substantia nigra of control and Parkinson’s disease. Brain Res Mol Brain Res 36(1):157–162
Tolosa E, Coelho M, Gallardo M (2003) DAT imaging in drug-induced and psychogenic parkinsonism. Mov Disord 18(Suppl 7):S28–S33
Berendse HW, Ponsen MM (2009) Diagnosing premotor Parkinson’s disease using a two-step approach combining olfactory testing and DAT SPECT imaging Parkinsonism. Parkinsonism Relat Disord 15(Suppl 3):S26–S30. doi:10.1016/S1353-8020(09)70774-6
Acknowledgments
This project was supported, in part, by the Chinese National Science Foundation (No. 30500208) and IAEA Research Project (No. CPR-13305).
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There is no conflict of interest between all authors.
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All experiments were reviewed by the Ethics Committee of the 148th Hospital.
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Li, JF., Yin, HL., Shuboy, A. et al. Differentiation of hUC-MSC into dopaminergic-like cells after transduction with hepatocyte growth factor. Mol Cell Biochem 381, 183–190 (2013). https://doi.org/10.1007/s11010-013-1701-z
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DOI: https://doi.org/10.1007/s11010-013-1701-z