Neurochemical Research

, Volume 35, Issue 10, pp 1522–1529 | Cite as

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

  • Ming Li
  • Shi-Zhong Zhang
  • Yan-Wu Guo
  • Ying-qian Cai
  • Zhong-jie Yan
  • Zhihao Zou
  • Xiao-Dan Jiang
  • Yi-Quan Ke
  • Xu-ying He
  • Zeng-liang Jin
  • Guo-hui Lu
  • Dao-qing Su
ORIGINAL PAPER

Abstract

Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson’s disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.

Keywords

Human umbilical vein mesenchymal stem cells Dopaminergic-like cells Cell differentiation Cell transplantation Parkinson’s disease 

References

  1. 1.
    Romanov YA, Svintsitskaya VA, Smirnov VN (2003) Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 21(1):105–110CrossRefPubMedGoogle Scholar
  2. 2.
    Covas DT, Siufi JL, Silva AR, Orellana MD (2003) Isolation and culture of umbilical vein mesenchymal stem cells. Braz J Med Biol Res 36:1179–1183CrossRefPubMedGoogle Scholar
  3. 3.
    Troyer DL, Weiss ML (2008) Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 26(3):591–599CrossRefPubMedGoogle Scholar
  4. 4.
    Kadivar M, Khatami S, Mortazavi Y, Shokrgozar MA, Taghikhani M, Soleimani M (2006) In vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells. Biochem Biophys Res Commun 340(2):639–647CrossRefPubMedGoogle Scholar
  5. 5.
    Abousleiman RI, Reyes Y, McFetridge P, Sikavitsas V (2008) The human umbilical vein: a novel scaffold for musculoskeletal soft tissue regeneration. Artif Organs 32(9):735–742CrossRefPubMedGoogle Scholar
  6. 6.
    Zucconi E, Vieira NM, Bueno DF, Secco M, Jazedje T, Ambrosio CE, Passos-Bueno MR, Miglino MA, Zatz M (2010) Mesenchymal stem cells derived from canine umbilical cord vein-A novel source for cell therapy studies. Stem Cells Dev 19(3):395–402CrossRefPubMedGoogle Scholar
  7. 7.
    Ishige I, Nagamura-Inoue T, Honda MJ, Harnprasopwat R, Kido M, Sugimoto M, Nakauchi H, Tojo A (2009) Comparison of mesenchymal stem cells derived from arterial, venous, and Wharton’s jelly explants of human umbilical cord. Int J Hematol 90(2):261–269CrossRefPubMedGoogle Scholar
  8. 8.
    Brundin P, Barbin G, Isacson O, Mallat M, Chamak B, Prochiantz A, Gage FH, Björklund A (1985) Survival of intracerebrally grafted rat dopamine neurons previously cultured in vitro. Neurosci Lett 61(1–2):79–84CrossRefPubMedGoogle Scholar
  9. 9.
    Nikkhah G, Olsson M, Eberhard J, Bentlage C, Cunningham MG, Björklund A (1994) A microtransplantation approach for cell suspension grafting in the rat Parkinson model. A detailed account of the methodology. Neuroscience 63(1):57–72CrossRefPubMedGoogle Scholar
  10. 10.
    Chaturvedi RK, Shukla S, Seth K, Agrawal AK (2006) Nerve growth factor increases survival of dopaminergic graft, rescue nigral dopaminergic neurons and restores functional deficits in rat model of Parkinson’s disease. Neurosci Lett 398(1–2):44–49CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang S, Zou Z, Jiang X, Xu R, Zhang W, Zhou Y, Ke Y (2008) The therapeutic effects of tyrosine hydroxylase gene transfected hematopoetic stem cells in a rat model of Parkinson’s disease. Cell Mol Neurobiol 28(4):529–543CrossRefPubMedGoogle Scholar
  12. 12.
    Zhu R, Xu R, Jiang X, Cai Y, Zou Y, Du M, Qin L (2007) Expression profile of cancer-related genes in human adult bone marrow-derived neural stemlike cells highlights the need for tumorigenicity study. J Neurosci Res 85(14):3064–3070CrossRefPubMedGoogle Scholar
  13. 13.
    Riaz SS, Theofilopoulos S, Jauniaux E, Stern GM, Bradford HF (2004) The differentiation potential of human foetal neuronal progenitor cells in vitro. Brain Res Dev Brain Res 153(1):39–51PubMedGoogle Scholar
  14. 14.
    Lee MW, Moon YJ, Yang MS, Kim SK, Jang IK, Eom YW, Park JS, Kim HC, Song KY, Park SC, Lim HS, Kim YJ (2007) Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun 358(2):637–643CrossRefPubMedGoogle Scholar
  15. 15.
    Nguyen TH, Khakhoulina T, Simmons A, Morel P, Trono D (2005) A simple and highly effective method for the stable transduction of uncultured porcine hepatocytes using lentiviral vector. Cell Transplant 14(7):489–496CrossRefPubMedGoogle Scholar
  16. 16.
    Shimizu S, Kitada M, Ishikawa H, Itokazu Y, Wakao S, Dezawa M (2007) Peripheral nerve regeneration by the in vitro differentiated-human bone marrow stromal cells with Schwann cell property. Biochem Biophys Res Commun 359(4):915–920CrossRefPubMedGoogle Scholar
  17. 17.
    Paxinos G, Watson C (1998) The rat brain in stereotatic coordinates, 2nd edn. Academic Press, Burlington, MAGoogle Scholar
  18. 18.
    Shetty P, Ravindran G, Sarang S, Thakur AM, Rao HS, Viswanathan C (2009) Clinical grade mesenchymal stem cells transdifferentiated under xenofree conditions alleviates motor deficiencies in a rat model of Parkinson’s disease. Cell Biol Int 33(8):830–838CrossRefPubMedGoogle Scholar
  19. 19.
    Zou Z, Zhang S, Jiang X (2006) Experimental study on establishment of PD’s rats model by 6-OHDA directional injection. Chi J Neuromed 5(3):244–247Google Scholar
  20. 20.
    Shimada H, Yoshimura N, Tsuji A, Kunisada T (2009) Differentiation of dopaminergic neurons from human embryonic stem cells: modulation of differentiation by FGF-20. J Biosci Bioeng 107(4):447–454CrossRefPubMedGoogle Scholar
  21. 21.
    Cho MS, Hwang DY, Kim DW (2008) Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale. Nat Protoc 3(12):1888–1894CrossRefPubMedGoogle Scholar
  22. 22.
    Chiba S, Lee YM, Zhou W, Freed CR (2008) Noggin enhances dopamine neuron production from human embryonic stem cells and improves behavioral outcome after transplantation into Parkinsonian rats. Stem Cells 26(11):2810–2820CrossRefPubMedGoogle Scholar
  23. 23.
    Nagane K, Kitada M, Wakao S, Dezawa M, Tabata Y (2009) Practical induction system for dopamine-producing cells from bone marrow stromal cells using spermine-pullulan-mediated reverse transfection method. Tissue Eng Part A 15(7):1655–1665CrossRefPubMedGoogle Scholar
  24. 24.
    Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE (2005) Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells 23(2):220–229CrossRefPubMedGoogle Scholar
  25. 25.
    Fu YS, Cheng YC, Lin MY, Cheng H, Chu PM, Chou SC, Shih YH, Ko MH, Sung MS (2006) Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 24(1):115–124CrossRefPubMedGoogle Scholar
  26. 26.
    Liu S, Tian Z, Yin F, Zhao Q, Fan M (2009) Generation of dopaminergic neurons from human fetal mesencephalic progenitors after co-culture with striatal-conditioned media and exposure to lowered oxygen. Brain Res Bull 80(1–2):62–68CrossRefPubMedGoogle Scholar
  27. 27.
    Andereggen L, Meyer M, Guzman R, Ducray AD, Widmer HR (2009) Effects of GDNF pretreatment on function and survival of transplanted fetal ventral mesencephalic cells in the 6-OHDA rat model of Parkinson’s disease. Brain Res 1276:39–49CrossRefPubMedGoogle Scholar
  28. 28.
    Grandoso L, Ponce S, Manuel I, Arrúe A, Ruiz-Ortega JA, Ulibarri I, Orive G, Hernández RM, Rodríguez A, Rodríguez-Puertas R, Zumárraga M, Linazasoro G, Pedraz JL, Ugedo L (2007) Long-term survival of encapsulated GDNF secreting cells implanted within the striatum of parkinsonized rats. Int J Pharm 343(1–2):69–78CrossRefPubMedGoogle Scholar
  29. 29.
    Yu Y, Gu S, Huang H, Wen T (2007) Combination of bFGF, heparin and laminin induce the generation of dopaminergic neurons from rat neural stem cells both in vitro and in vivo. J Neurol Sci 255(1–2):81–86CrossRefPubMedGoogle Scholar
  30. 30.
    Nakao N, Frodl EM, Duan WM, Widner H, Brundin P (1994) Lazaroids improve the survival of grafted rat embryonic dopamine neurons. Proc Natl Acad Sci USA 91(26):12408–12412CrossRefPubMedGoogle Scholar
  31. 31.
    Schierle GS, Hansson O, Leist M, Nicotera P, Widner H, Brundin P (1999) Caspase inhibition reduces apoptosis and increases survival of nigral transplants. Nat Med 5(1):97–100CrossRefPubMedGoogle Scholar
  32. 32.
    Nikkhah G, Cunningham MG, Cenci MA, McKay RD, Björklund A (1995) Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. I. Evidence for anatomical reconstruction of the nigrostriatal pathway. J Neurosci 15(5 Pt 1):3548–3561PubMedGoogle Scholar
  33. 33.
    Ma CH, Palmer A, Taylor JS (2009) Synergistic effects of osteonectin and NGF in promoting survival and neurite outgrowth of superior cervical ganglion. Brain Res 1289:1–13CrossRefPubMedGoogle Scholar
  34. 34.
    Wang TH, Feng ZT, Wei P, Li H, Shi ZJ, Li LY (2008) Effects of pcDNA3-beta-NGF gene-modified BMSC on the rat model of Parkinson’s disease. J Mol Neurosci 35(2):161–169CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ming Li
    • 1
    • 2
  • Shi-Zhong Zhang
    • 1
    • 2
  • Yan-Wu Guo
    • 1
    • 2
  • Ying-qian Cai
    • 1
    • 2
  • Zhong-jie Yan
    • 1
    • 2
  • Zhihao Zou
    • 1
    • 2
    • 3
  • Xiao-Dan Jiang
    • 1
    • 2
  • Yi-Quan Ke
    • 1
    • 2
  • Xu-ying He
    • 1
    • 2
  • Zeng-liang Jin
    • 4
  • Guo-hui Lu
    • 1
    • 2
  • Dao-qing Su
    • 1
    • 2
  1. 1.Department of Neurosurgery, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Institute of Neurosurgery, Key Laboratory on Brain Function Repair and Regeneration of GuangdongSouthern Medical UniversityGuangzhouChina
  3. 3.Department of NeurosurgeryThe 474th Militrary HospitalWulumuqiChina
  4. 4.Department of Pharmacology, School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouChina

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