Neurochemical Research

, Volume 38, Issue 12, pp 2483–2489 | Cite as

Electrophysiological Characterisation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Induced by Olfactory Ensheathing Cell-Conditioned Medium

  • Yu Zeng
  • Mingqiang Rong
  • Yunsheng Liu
  • Jingfang Liu
  • Ming Lu
  • Xiaoyu Tao
  • Zhenyan Li
  • Xin Chen
  • Kui Yang
  • Chuntao Li
  • Zhixiong Liu
Original Paper


Umbilical cord blood-derived marrow stromal cells (UCB-MSCs) with high proliferation capacity and immunomodulatory properties are considered to be a good candidate for cell-based therapies. But until now, little work has been focused on the differentiation of UCB-MSCs. In this work, UCB-MSCs were demonstrated to be negative for CD34 and CD45 expression but positive for CD90 and CD105 expression. The gate values of UCB-MSCs for CD90 and CD105 were 99.3 and 98.6 %, respectively. Two weeks after treatment, the percentage of neuron-like cells differentiated from UCB-MSCs was increased to 84 ± 12 % in the experimental group [treated with olfactory ensheathing cells (OECs)-conditioned medium] and they were neuron-specific enolase positive; few neuron-like cells were found in the control group (without OECs-conditioned medium). Using whole-cell recording, sodium and potassium currents were recorded in UCB-MSCs after differentiation by OECs. Thus, human UCB-MSCs could be differentiated to neural cells by secreted secretion from OECs and exhibited electrophysiological properties similar to mature neurons after 2 weeks post-induction. These results imply that OECs can be used as a new strategy for stem cell differentiation and provide an alternative neurogenesis pathway for generating sufficient numbers of neural cells for cell therapy.


Stem cell Differentiation Olfactory ensheathing cells Ion channel 


Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Ao Q, Wang AJ, Chen GQ, Wang SJ, Zuo HC, Zhang XF (2007) Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries. Med Hypotheses 69:1234–1237PubMedCrossRefGoogle Scholar
  2. 2.
    Bieback K, Kern S, Klüter H, Eichler H (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22:525–634CrossRefGoogle Scholar
  3. 3.
    Capelli C, Gotti E, Morigi M, Rota C, Weng L, Dazzi F, Spinelli O, Cazzaniga G, Trezzi R, Gianatti A, Rambaldi A, Golay J, Introna M (2011) Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate. Cytotherapy 13:786–801PubMedCrossRefGoogle Scholar
  4. 4.
    Duan D, Rong M, Zeng Y, Teng X, Zhao Z, Liu B, Tao X, Zhou R, Fan M, Peng C, Chen P, Liang S, Lu M (2011) Electrophysiological characterization of NSCs after differentiation induced by OEC conditioned medium. Acta Neurochir (Wien) 153:2085–2090CrossRefGoogle Scholar
  5. 5.
    Erices A, Conget P, Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109:235–242PubMedCrossRefGoogle Scholar
  6. 6.
    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 24:115–124PubMedCrossRefGoogle Scholar
  7. 7.
    Gang EJ, Hong SH, Jeong JA, Hwang SH, Kim SW, Yang IH, Ahn C, Han H, Kim H (2004) In vitro mesengenic potential of human umbilical cord blood-derived mesenchymal stem cells. Biochem Biophys Res Commun 321:102–108PubMedCrossRefGoogle Scholar
  8. 8.
    Goldman S (2005) Stem and progenitor cell-based therapy of the human central nervous system. Nat Biotechnol 23:862–871PubMedCrossRefGoogle Scholar
  9. 9.
    Greco SJ, Zhou C, Ye JH, Rameshwar P (2007) An interdisciplinary approach and characterization of neuronal cells transdifferentiated from human mesenchymal stem cells. Stem Cells Dev 16:811–826PubMedCrossRefGoogle Scholar
  10. 10.
    Harris DT (2008) Cord blood stem cells: a review of potential neurological applications. Stem Cell Res 4:269–274CrossRefGoogle Scholar
  11. 11.
    Jurga M, Lipkowski AW, Lukomska B, Buzanska L, Kurzepa K, Sobanski T, Habich A, Coecke S, Gajkowska B, Domanska-Janik K (2009) Generation of functional neural artificial tissue from human umbilical cord blood stem cells. Tissue Eng Part C Methods 15:365–372PubMedCrossRefGoogle Scholar
  12. 12.
    Koch TG, Heerkens T, Thomsen PD, Betts DH (2007) Isolation of mesenchymal stem cells from equine umbilical cord blood, BMC. Biotechnology 7:1–9Google Scholar
  13. 13.
    Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH (2004) Isolation of multipotentmesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675PubMedCrossRefGoogle Scholar
  14. 14.
    Lee H, Bae JS, Jin HK (2010) Human umbilical cord blood-derived mesenchymal stem cells improve neurological abnormalities of Niemann-Pick type C mouse by modulation of neuroinflammatory condition. J Vet Med Sci 72:709–717PubMedCrossRefGoogle Scholar
  15. 15.
    Lee HJ, Lee JK, Lee H, Carter JE, Chang WJ, Oh W, Yang YS, Suh JG, Lee BH, Jin HK, Bae JS (2012) Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer’s disease mouse model through modulation of neuroinflammation. Neurobiol Aging 33:588–602PubMedCrossRefGoogle Scholar
  16. 16.
    Liu Y, Teng X, Yang X, Song Q, Lu R, Xiong J, Liu B, Zeng N, Zeng Y, Long J, Cao R, Lin Y, He Q, Chen P, Lu M, Liang S (2010) Shotgun proteomics and network analysis between plasma membrane and extracellular matrix proteins from rat olfactory ensheathing cells. Cell Transpl 19:133–146CrossRefGoogle Scholar
  17. 17.
    Moore NH, Costa LG, Shaffer SA, Goodlett DR, Guizzetti M (2009) Shotgun proteomics implicates extracellular matrix proteins and protease systems in neuronal development induced by astrocyte cholinergic stimulation. J Neurochem 108:891–908PubMedCrossRefGoogle Scholar
  18. 18.
    Ni WF, Yin LH, Lu J, Xu HZ, Chi YL, Wu JB, Zhang N (2010) In vitro neural differentiation of bone marrow stromal cells induced by Cocultured olfactory ensheathing cells. Neurosci Lett 475:99–103PubMedCrossRefGoogle Scholar
  19. 19.
    Park SI, Lim JY, Jeong CH, Kim SM, Jun JA, Jeun SS, Oh WI (2012) Human umbilical cord blood-derived mesenchymal stem cell therapy promotes functional recovery of contused rat spinal cord through enhancement of endogenous cell proliferation and oligogenesis. J Biomed Biotechnol 2012:362473PubMedGoogle Scholar
  20. 20.
    Peters R, Wolf MJ, van den Broek M, Nuvolone M, Dannenmann S, Stieger B, Rapold R, Konrad D, Rubin A, Bertino JR, Aguzzi A, Heikenwalder M, Knuth AK (2010) Efficient generation of multipotentmesenchymal stem cells from umbilical cord blood in stroma-free liquid culture. PLoS One 5:e15689PubMedCrossRefGoogle Scholar
  21. 21.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  22. 22.
    Quirici N, Soligo D, Bossolasco P, Servida F, Lumini C, Deliliers GL (2002) Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp Hematol l30:783–791CrossRefGoogle Scholar
  23. 23.
    Rao MS, Mattson MP (2001) Stem cells and aging: expanding the possibilities. Mech Ageing Dev 1227:13–734Google Scholar
  24. 24.
    Rojas-Mayorquín AE, Torres-Ruíz NM, Ortuño-Sahagún D, Gudiño-Cabrera G (2008) Microarray analysis of striatal embryonic stem cells induced to differentiate by ensheathing cell conditioned media. Dev Dyn 237:979–994PubMedCrossRefGoogle Scholar
  25. 25.
    Sanchez-Ramos JR, Song S, Kamath SG, Zigova T, Willing A, Cardozo-Pelaez F, Stedeford T, Chopp M, Sanberg PR (2001) Expression of neural markers in human umbilical cord blood. Exp Neurol 171:109–115PubMedCrossRefGoogle Scholar
  26. 26.
    Shukla S, Chaturvedi RK, Seth K, Roy NS, Agrawal AK (2009) Enhanced survival and function of neural stem cells-derived dopaminergic neurons under influence of olfactory ensheathing cells in parkinsonian rats. J Neurochem 109:436–451PubMedCrossRefGoogle Scholar
  27. 27.
    Srivastava N, Seth K, Khanna VK, Ansari RW, Agrawal AK (2009) Long-term functional restoration by neural progenitor cell transplantation in rat model of cognitive dysfunction: co-transplantation with olfactory ensheathing cells for neurotrophic factor support. Int J Dev Neurosci 27:103–110PubMedCrossRefGoogle Scholar
  28. 28.
    Tio M, Tan KH, Lee W, Wang TT, Udolph G (2010) Roles of db-cAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymal-like stem cells. PLoS One 5:e9398PubMedCrossRefGoogle Scholar
  29. 29.
    Torrente Y, Polli E (2008) Mesenchymal stem cell transplantation for neurodegenerative diseases. Cell Transpl 17:1103–1113CrossRefGoogle Scholar
  30. 30.
    Yang SE, Ha CW, Jung M, Jin HJ, Lee M, Song H, Choi S, Oh W, Yang YS (2004) Mesenchymal stem/progenitor cells developed in cultures from UC blood. Cytotherapy 6:476–486PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yu Zeng
    • 1
  • Mingqiang Rong
    • 2
  • Yunsheng Liu
    • 1
  • Jingfang Liu
    • 1
  • Ming Lu
    • 3
  • Xiaoyu Tao
    • 3
  • Zhenyan Li
    • 1
  • Xin Chen
    • 1
  • Kui Yang
    • 1
  • Chuntao Li
    • 1
  • Zhixiong Liu
    • 1
  1. 1.Department of Neurosurgery, Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Kunming Institute of ZoologyChinese Academy of SciencesKunmingChina
  3. 3.Department of NeurosurgerySecond Affiliated Hospital of Hunan Normal UniversityChangshaChina

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