Neurochemical Research

, Volume 34, Issue 11, pp 2030–2039 | Cite as

Cografted Wharton’s Jelly Cells-derived Neurospheres and BDNF Promote Functional Recovery After Rat Spinal Cord Transection

  • Liang Zhang
  • Hong-Tian Zhang
  • Sun-Quan Hong
  • Xu Ma
  • Xiao-Dan Jiang
  • Ru-Xiang XuEmail author
Original Paper


An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted human umbilical mesenchymal stem cells-derived neurospheres (HUMSC-NSs) and BDNF can promote morphologic and functional recoveries of injured spinal cord. In vitro, HUMSC-NSs terminally differentiated into higher percentages of cells expressing neuronal markers: β-tubulin III and MAP2ab by the supplement with BDNF. Following grafted into injured spinal cord, very few grafted cells survived in the HUMSC-NSs + BDNF-treated (<3%) and HUMSC-NSs-treated (<1%) groups. The survived cells were differentiated into various cells, which were confirmed by double staining of BrdU and neural or glia markers. In comparison, more grafted cells in the HUMSC-NSs + BDNF group transformed into mature neural-like cells, while more grafted cells in the HUMSC-NSs group transformed into oligodendrocyte-like cells. HUMSC-NSs + BDNF-treated group had more greatly improved BBB scores, compared with HUMSC-NSs-treated and medium-treated groups. Additionally, axonal regeneration showed significant improvement in rats receiving HUMSC-NSs + BDNF, compared with HUMSC-NSs-treated and medium-treated groups, as demonstrated by the NF-200-positive staining and Fluorogold (FG) retrograde tracing study. Lastly, a significant reduction in the percentage cavitation was seen in the two cell-treated groups compared with medium control group. These results means BDNF could promote the neural differentiation of HUMSC-NSs in vitro and in vivo. However, cellular replacement is unlikely to explain the improvement in functional outcome. The functional recovery might more rely on the axonal regeneration and neuroprotective action that active by the grafted cells. Cografted HUMSCs and BDNF is a potential therapy for SCI.


Wharton’s jelly cells Umbilical mesenchymal stem cells BDNF Transplantation Spinal cord injury 



We thank Health & Biotech (Guangdong, Guangzhou, China) for them kindly present human umbilical mesenchymal stem cells. This research was supported by Natural Science Found of China (NSFC) (U0632008, 30772232, 30801184), Foundations for Key Sci-Tech Research Projects of Guangdong Province [2006Z3-E522, YUE KEJIBAN (2007) 05/06-7005206, 05/06-7005213,YUECAIJIAO (2008) 258-2008A030201019], and Foundations for Key Sci-Tech Research Projects of Guangzhou [YUEKETIAOZI (2008)3-2008A1-E4011-6].


  1. 1.
    Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L et al (2003) Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 21(1):50–60PubMedGoogle Scholar
  2. 2.
    Yang CC, Shih YH, Ko MH, Hsu SY, Cheng H, Fu YS (2008) Transplantation of human umbilical mesenchymal stem cells from Wharton’s jelly after complete transection of the rat spinal cord. PLoS One 3(10):3336. doi: 10.1371/journal.pone.0003336 CrossRefGoogle Scholar
  3. 3.
    Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ et al (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22(7):1330–1337. doi: 10.1634/stemcells.2004-0013 PubMedCrossRefGoogle Scholar
  4. 4.
    Troyer DL, Weiss ML (2008) Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 26(3):591–599. doi: 10.1634/stemcells.2007-0439 PubMedCrossRefGoogle Scholar
  5. 5.
    Fu YS, Cheng YC, Lin MY, Cheng H, Chu PM, Chou SC et al (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):115–124. doi: 10.1634/stemcells.2005-0053 PubMedCrossRefGoogle Scholar
  6. 6.
    Chao KC, Chao KF, Fu YS, Liu SH (2008) Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One 3(1):e1451. doi: 10.1371/journal.pone.0001451 PubMedCrossRefGoogle Scholar
  7. 7.
    Fu YS, Shih YT, Cheng YC, Min MY (2004) Transformation of human umbilical mesenchymal cells into neurons in vitro. J Biomed Sci 11(5):652–660. doi: 10.1007/BF02256131 PubMedCrossRefGoogle Scholar
  8. 8.
    Kwon BK, Liu J, Lam C, Plunet W, Oschipok LW, Hauswirth W et al (2007) Brain-derived neurotrophic factor gene transfer with adeno-associated viral and lentiviral vectors prevents rubrospinal neuronal atrophy and stimulates regeneration-associated gene expression after acute cervical spinal cord injury. Spine 32(11):1164–1173. doi: 10.1097/BRS.0b013e318053ec35 PubMedCrossRefGoogle Scholar
  9. 9.
    Shumsky JS, Tobias CA, Tumolo M, Long WD, Giszter SF, Murray M (2003) Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp Neurol 184(1):114–130. doi: 10.1016/S0014-4886(03)00398-4 PubMedCrossRefGoogle Scholar
  10. 10.
    Song XY, Li F, Zhang FH, Zhong JH, Zhou XF (2008) Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury. PLoS ONE 3(3):e1707PubMedCrossRefGoogle Scholar
  11. 11.
    Hermann A, Gastl R, Liebau S, Popa MO, Fiedler J, Boehm BO et al (2004) Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. J Cell Sci 117(Pt 19):4411–4422. doi: 10.1242/jcs.01307 PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang HT, Cheng HY, Cai YQ, Ma X, Liu WP, Yan ZJ, et al (2009) Comparison of adult neurospheres derived from different origins for treatment of rat spinal cord injury. Neurosci Lett 458(3):116–121. doi: 10.1016/jneulet.2009.04.045 PubMedCrossRefGoogle Scholar
  13. 13.
    Basso DM, Beattie MS, Bresnahan JC, Anderson DK, Faden AI, Gruner JA et al (1996) MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter animal spinal cord injury study. J Neurotrauma 13(7):343–359. doi: 10.1089/neu.1996.13.343 PubMedCrossRefGoogle Scholar
  14. 14.
    Hains BC, Saab CY, Lo AC, Waxman SG (2004) Sodium channel blockade with phenytoin protects spinal cord axons, enhances axonal conduction, and improves functional motor recovery after contusion SCI. Exp Neurol 188(2):365–377. doi: 10.1016/j.expneurol.2004.04.001 PubMedCrossRefGoogle Scholar
  15. 15.
    Reier PJ (2004) Cellular transplantation strategies for spinal cord injury and translational neurobiology. NeuroRx 1(4):424–451. doi: 10.1602/neurorx.1.4.424 PubMedCrossRefGoogle Scholar
  16. 16.
    Parr AM, Kulbatski I, Zahir T, Wang X, Yue C, Keating A et al (2008) Transplanted adult spinal cord-derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury. Neuroscience 155(3):760–770. doi: 10.1016/j.neuroscience.2008.05.042 PubMedCrossRefGoogle Scholar
  17. 17.
    Vaquero J, Zurita M (2009) Bone marrow stromal cells for spinal cord repair: a challenge for contemporary neurobiology. Histol Histopathol 24(1):107–116PubMedGoogle Scholar
  18. 18.
    Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J et al (2002) Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology 22(4):275–279. doi: 10.1046/j.1440-1789.2002.00450.x PubMedCrossRefGoogle Scholar
  19. 19.
    Kirschenbaum B, Goldman SA (1995) Brain-derived neurotrophic factor promotes the survival of neurons arising from the adult rat forebrain subependymal zone. Proc Natl Acad Sci USA 92(1):210–214. doi: 10.1073/pnas.92.1.210 PubMedCrossRefGoogle Scholar
  20. 20.
    Kuh SU, Cho YE, Yoon DH, Kim KN, Ha Y (2005) Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochir (Wien) 147(9):985–992. doi: 10.1007/s00701-005-0538-y (discussion 992)CrossRefGoogle Scholar
  21. 21.
    Mahmood A, Lu D, Wang L, Chopp M (2002) Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. J Neurotrauma 19(12):1609–1617. doi: 10.1089/089771502762300265 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Liang Zhang
    • 1
    • 2
    • 4
  • Hong-Tian Zhang
    • 1
    • 2
    • 3
  • Sun-Quan Hong
    • 1
    • 2
  • Xu Ma
    • 1
    • 2
  • Xiao-Dan Jiang
    • 1
    • 2
  • Ru-Xiang Xu
    • 1
    • 2
    • 3
    Email author
  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 Military General Hospital of Beijing, PLABeijingChina
  4. 4.Department of NeurosurgeryGuangzhou Brain HospitalGuangzhouChina

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