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Differentiation of hUC-MSC into dopaminergic-like cells after transduction with hepatocyte growth factor

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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

  1. Pluck GC, Brown RG (2002) Apathy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73(6):636–642

    Article  PubMed  CAS  Google Scholar 

  2. Bjorklund A, Kordower JH (2013) Cell therapy for Parkinson’s disease: what next? Mov Disord 28(1):110–115. doi:10.1002/mds.25343

    Article  PubMed  CAS  Google Scholar 

  3. 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

    Article  PubMed  CAS  Google Scholar 

  4. 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

    Article  PubMed  CAS  Google Scholar 

  5. 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

    Article  PubMed  CAS  Google Scholar 

  6. Pedrosa DJ, Timmermann L (2013) Review: management of Parkinson’s disease. Neuropsychiatr Dis Treat 9:321–340. doi:10.2147/NDT.S32302

    Article  PubMed  Google Scholar 

  7. 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

    Article  PubMed  CAS  Google Scholar 

  8. Michalopoulos GK, Zarnegav R (1992) Hepatocyte growth factor. Hepatology 15(1):149–155

    Article  PubMed  CAS  Google Scholar 

  9. 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

    Article  PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. 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

    Article  PubMed  CAS  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. 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

    Article  PubMed  CAS  Google Scholar 

  14. 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

    Article  PubMed  CAS  Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. Gaiba S, França LP, França JP, Ferreira LM (2012) Characterization of human adipose-derived stem cells. Acta Cir Bras 27(7):471–476

    Article  PubMed  Google Scholar 

  19. 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

    Article  PubMed  CAS  Google Scholar 

  20. 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

    Article  Google Scholar 

  21. 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

    Article  PubMed  CAS  Google Scholar 

  22. 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

    Article  PubMed  Google Scholar 

  23. 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

    Article  CAS  Google Scholar 

  24. Phinney DG, Isakova I (2005) Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 11(10):1255–1265

    Article  PubMed  CAS  Google Scholar 

  25. 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

    Article  PubMed  CAS  Google Scholar 

  26. 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

    PubMed  CAS  Google Scholar 

  27. Fiszer U (2001) Does Parkinson’s disease have an immunological basis? The evidence and its therapeutic implications. BioDrugs 15(6):351–355

    Article  PubMed  CAS  Google Scholar 

  28. 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

    Article  PubMed  CAS  Google Scholar 

  29. 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

    Article  PubMed  CAS  Google Scholar 

  30. 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

    Article  PubMed  CAS  Google Scholar 

  31. 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

    Article  PubMed  CAS  Google Scholar 

  32. 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

    Article  PubMed  CAS  Google Scholar 

  33. 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

    Article  PubMed  CAS  Google Scholar 

  34. Tolosa E, Coelho M, Gallardo M (2003) DAT imaging in drug-induced and psychogenic parkinsonism. Mov Disord 18(Suppl 7):S28–S33

    Article  PubMed  Google Scholar 

  35. 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

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This project was supported, in part, by the Chinese National Science Foundation (No. 30500208) and IAEA Research Project (No. CPR-13305).

Conflict of interest

There is no conflict of interest between all authors.

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Correspondence to Hong-wei Wang or Yun-Liang Wang.

Additional information

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

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