Skip to main content

Advertisement

SpringerLink
Log in

Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat

  • Experimental Research
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Summary

There have been many efforts to recover neuronal function from spinal cord injuries, but there are some limitations in the treatment of spinal cord injuries.

The neural stem cell has been noted for its pluripotency to differentiate into various neural cell types. The human umbilical cord blood cells (HUCBs) are more pluripotent and genetically flexible than bone marrow neural stem cells. The HUCBs could be more frequently used for spinal cord injury treatment in the future.

Moderate degree spinal cord injured rats were classified into 3 subgroups, group A: media was injected into the cord injury site, group B: HUCBs were transplanted into the cord injury site, and group C: HUCBs with BDNF (Brain-derived neutrophic factor) were transplanted into the cord injury site. We checked the BBB scores to evaluate the functional recovery in each group at 8 weeks after transplantation. We then, finally checked the neural cell differentiation with double immunofluorescence staining, and we also analyzed the axonal regeneration with retrograde labelling of brain stem neurons by using fluorogold. The HUCBs transplanted group improved, more than the control group at every week after transplantation, and also, the BDNF enabled an improvement of the BBB locomotion scores since the 1 week after its application (P<0.05). 8 weeks after transplantation, the HUCBs with BDNF transplanted group had more greatly improved BBB scores, than the other groups (P<0.001). The transplanted HUCBs were differentiated into various neural cells, which were confirmed by double immunoflorescence staining of BrdU and GFAP & MAP-2 staining. The HUCBs and BDNF each have individual positive effects on axonal regeneration. The HUCBs can differentiate into neural cells and induce motor function improvement in the cord injured rat models. Especially, the BDNF has effectiveness for neurological function improvement due to axonal regeneration in the early cord injury stage. Thus the HUCBs and BDNF have recovery effects of a moderate degree for cord injured rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • DM Basso MS Beattie JC Bresnahan DK Anderson AI Faden JA Gruner et al. (1996) ArticleTitleMASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study. J Neurotrauma 13 343–359 Occurrence Handle8863191

    PubMed  Google Scholar 

  • H Bernstein-Goral BS Bregman (1993) ArticleTitleSpinal cord transplants support the regeneration of axotomized neurons after spinal cord lesions at birth: a quantitative double-labeling study. Exp Neurol 123 118–132 Occurrence Handle10.1006/exnr.1993.1145 Occurrence Handle8405272

    Article  PubMed  Google Scholar 

  • AR Bicknese HS Goodwin CO Quinn VC Henderson SN Chien DA Wall (2002) ArticleTitleHuman umbilical cord blood cells can be induced to express markers for neurons and glia. Cell Transplant 11 261–264 Occurrence Handle12075991

    PubMed  Google Scholar 

  • A Blesch P Lu MH Tuszynski (2002) ArticleTitleNeurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain Res Bull 57 833–838 Occurrence Handle10.1016/S0361-9230(01)00774-2 Occurrence Handle12031281

    Article  PubMed  Google Scholar 

  • BS Bregman M McAtee HN Dai PL Kuhn (1997) ArticleTitleNeurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat. Exp Neurol 148 475–494 Occurrence Handle10.1006/exnr.1997.6705 Occurrence Handle9417827

    Article  PubMed  Google Scholar 

  • L Buzanska EK Machaj B Zablocka Z Pojda K Domanska-Janik (2002) ArticleTitleHuman cord blood-derived cells attain neuronal and glial features in vitro. J Cell Sci 115 2131–2138 Occurrence Handle11973354

    PubMed  Google Scholar 

  • J Chen Y Li M Chopp (2000) ArticleTitleIntracerebral transplantation of bone marrow with BDNF after MCAo in rat. Neuropharmacology 39 711–716 Occurrence Handle10.1016/S0028-3908(00)00006-X Occurrence Handle10699437

    Article  PubMed  Google Scholar 

  • JV Coumans TT Lin HN Dai L MacArthur M McAtee C Nash et al. (2001) ArticleTitleAxonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J Neurosci 21 9334–9344 Occurrence Handle11717367

    PubMed  Google Scholar 

  • M Dezawa (2002) ArticleTitleCentral and peripheral nerve regeneration by transplantation of Schwann cells and transdifferentiated bone marrow stromal cells. Anat Sci Int 77 12–25 Occurrence Handle10.1046/j.0022-7722.2002.00012.x Occurrence Handle12418080

    Article  PubMed  Google Scholar 

  • PS Diener BS Bregman (1994) ArticleTitleNeurotrophic factors prevent the death of CNS neurons after spinal cord lesions in newborn rats. Neuroreport 5 1913–1917 Occurrence Handle7841375

    PubMed  Google Scholar 

  • RJ Franklin (2002) ArticleTitleRemyelination of the demyelinated CNS: the case for and against transplantation of central, peripheral and olfactory glia. Brain Res Bull 57 827–832 Occurrence Handle10.1016/S0361-9230(01)00765-1 Occurrence Handle12031280

    Article  PubMed  Google Scholar 

  • EL Goh D Ma GL Ming H Song (2003) ArticleTitleAdult neural stem cells and repair of the adult central nervous system. J Hematother Stem Cell Res 12 671–679 Occurrence Handle10.1089/15258160360732696 Occurrence Handle14977476

    Article  PubMed  Google Scholar 

  • HS Goodwin AR Bicknese SN Chien BD Bogucki CO Quinn DA Wall (2001) ArticleTitleMultilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers. Biol Blood Marrow Transplant 7 581–588 Occurrence Handle10.1053/bbmt.2001.v7.pm11760145 Occurrence Handle11760145

    Article  PubMed  Google Scholar 

  • JD Guest D Hesse L Schnell ME Schwab MB Bunge RP Bunge (1997) ArticleTitleInfluence of IN-1 antibody and acidic FGF-fibrin glue on the response of injured corticospinal tract axons to human Schwann cell grafts. J Neurosci Res 50 888–905 Occurrence Handle10.1002/(SICI)1097-4547(19971201)50:5<888::AID-JNR24>3.0.CO;2-W Occurrence Handle9418975

    Article  PubMed  Google Scholar 

  • Y Ha JU Choi DH Yoon DS Yeon JJ Lee HO Kim et al. (2001) ArticleTitleNeural phenotype expression of cultured human cord blood cells in vitro. Neuroreport 12 3523–3527 Occurrence Handle10.1097/00001756-200111160-00030 Occurrence Handle11733704

    Article  PubMed  Google Scholar 

  • FP Hamers AJ Lankhorst TJ van Laar WB Veldhuis WH Gispen (2001) ArticleTitleAutomated quantitative gait analysis during overground locomotion in the rat: its application to spinal cord contusion and transection injuries. J Neurotrauma 18 187–201 Occurrence Handle10.1089/08977150150502613 Occurrence Handle11229711

    Article  PubMed  Google Scholar 

  • JD Houle JH Ye (1997) ArticleTitleChanges occur in the ability to promote axonal regeneration as the post-injury period increases. Neuroreport 8 751–755 Occurrence Handle9106760

    PubMed  Google Scholar 

  • JD Houle JH Ye (1999) ArticleTitleSurvival of chronically-injured neurons can be prolonged by treatment with neurotrophic factors. Neuroscience 94 929–936 Occurrence Handle10.1016/S0306-4522(99)00359-0 Occurrence Handle10579585

    Article  PubMed  Google Scholar 

  • DA Houweling JT van Asseldonk AJ Lankhorst FP Hamers D Martin PR Bar et al. (1998) ArticleTitleLocal application of collagen containing brain-derived neurotrophic factor decreases the loss of function after spinal cord injury in the adult rat. Neurosci Lett 251 193–196 Occurrence Handle10.1016/S0304-3940(98)00536-9 Occurrence Handle9726376

    Article  PubMed  Google Scholar 

  • K Ishii M Toda Y Nakai H Asou M Watanabe M Nakamura et al. (2001) ArticleTitleIncrease of oligodendrocyte progenitor cells after spinal cord injury. J Neurosci Res 65 500–507 Occurrence Handle10.1002/jnr.1180 Occurrence Handle11550218

    Article  PubMed  Google Scholar 

  • BK Kwon W Tetzlaff (2001) ArticleTitleSpinal cord regeneration: from gene to transplants. Spine 26 S13–S22 Occurrence Handle10.1097/00007632-200112151-00003 Occurrence Handle11805602

    Article  PubMed  Google Scholar 

  • P Lu LL Jones EY Snyder MH Tuszynski (2003) ArticleTitleNeural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 181 115–129 Occurrence Handle10.1016/S0014-4886(03)00037-2 Occurrence Handle12781986

    Article  PubMed  Google Scholar 

  • JW McDonald MJ Howard (2002) ArticleTitleRepairing the damaged spinal cord: a summary of our early success with embryonic stem cell transplantation and remyelination. Prog Brain Res 137 299–309 Occurrence Handle12449097

    PubMed  Google Scholar 

  • GA Metz D Merkler V Dietz ME Schwab K Fouad (2000) ArticleTitleEfficient testing of motor function in spinal cord injured rats. Brain Res 883 165–177 Occurrence Handle10.1016/S0006-8993(00)02778-5 Occurrence Handle11074045

    Article  PubMed  Google Scholar 

  • T Murakami Y Fujimoto Y Yasunaga O Ishida N Tanaka Y Ikuta et al. (2003) ArticleTitleTransplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair. Brain Res 974 17–24 Occurrence Handle10.1016/S0006-8993(03)02539-3 Occurrence Handle12742620

    Article  PubMed  Google Scholar 

  • M Nakamura Y Toyama (2003) ArticleTitleTransplantation of neural stem cells into spinal cord after injury. Nippon Rinsho 61 463–468

    Google Scholar 

  • A Privat (2003) ArticleTitleRepair of the mammalian central nervous system: the “spinal cord” model. Bull Acad Natl Med 187 345–357 Occurrence Handle14556445

    PubMed  Google Scholar 

  • JR Sanchez-Ramos (2002) ArticleTitleNeural cells derived from adult bone marrow and umbilical cord blood. J Neurosci Res 69 880–893 Occurrence Handle10.1002/jnr.10337 Occurrence Handle12205681

    Article  PubMed  Google Scholar 

  • SW Scheff DA Saucier ME Cain (2002) ArticleTitleA statistical method for analyzing rating scale data: the BBB locomotor score. J Neurotrauma 19 1251–1260 Occurrence Handle10.1089/08977150260338038 Occurrence Handle12427332

    Article  PubMed  Google Scholar 

  • U Slawinska (2002) ArticleTitleTransplants as a therapy after spinal cord injury. Neurol Neurochir Pol 36 IssueID[Suppl 1] 73–94 Occurrence Handle12189688

    PubMed  Google Scholar 

  • S Song J Sanchez-Ramos (2002) ArticleTitlePreparation of neural progenitors from bone marrow and umbilical cord blood. Methods Mol Biol 198 79–88 Occurrence Handle11951643

    PubMed  Google Scholar 

  • Y Sun J Shi SL Fu PH Lu XM Xu (2003) ArticleTitleEffects of embryonic neural stem cells and glial cell line-derived neurotrophic factor in the repair of spinal cord injury. Sheng Li Xue Bao 55 349–354 Occurrence Handle12817305

    PubMed  Google Scholar 

  • M Vroemen L Aigner J Winkler N Weidner (2003) ArticleTitleAdult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways. Eur J Neurosci 18 743–751 Occurrence Handle10.1046/j.1460-9568.2003.02804.x Occurrence Handle12925000

    Article  PubMed  Google Scholar 

  • NR West V Leblanc GH Collins (2001) ArticleTitleSupport of axonal regrowth by endogenous mechanisms following spinal cord injury in adult rats. Neuropathology 21 188–202 Occurrence Handle10.1046/j.1440-1789.2001.00398.x Occurrence Handle11666016

    Article  PubMed  Google Scholar 

  • S Woerly VD Doan F Evans-Martin CG Paramore JD Peduzzi (2001) ArticleTitleSpinal cord reconstruction using NeuroGel implants and functional recovery after chronic injury. J Neurosci Res 66 1187–1197 Occurrence Handle10.1002/jnr.1255 Occurrence Handle11746452

    Article  PubMed  Google Scholar 

  • XM Xu V Guenard N Kleitman P Aebischer MB Bunge (1995) ArticleTitleA combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol 134 261–272 Occurrence Handle10.1006/exnr.1995.1056 Occurrence Handle7556546

    Article  PubMed  Google Scholar 

  • T Zigova S Song AE Willing JE Hudson MB Newman S Saporta et al. (2002) ArticleTitleHuman umbilical cord blood cells express neural antigens after transplantation into the developing rat brain. Cell Transplant 11 265–274 Occurrence Handle12075992

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea

    S.-U. Kuh, Y.-E. Cho, D.-H. Yoon & K.-N. Kim

  2. Inha University College of Medicine, Seoul, Korea

    Y. Ha

Authors
  1. S.-U. Kuh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y.-E. Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D.-H. Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K.-N. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuh, SU., Cho, YE., Yoon, DH. et al. Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochir (Wien) 147, 985–992 (2005). https://doi.org/10.1007/s00701-005-0538-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00701-005-0538-y

Search

Navigation