The role of brain-derived neurotrophic factor in bone marrow stromal cell-mediated spinal cord repair

Gaby J. Ritfeld, Ajay Patel, Alexander Chou, Tabitha L. Novosat, Deborah G. Castillo, Raymund A.C. Roos, Martin Oudega

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


The ability of intraspinal bone marrow stromal cell (BMSC) transplants to elicit repair is thought to result from paracrine effects by secreted trophic factors including brain-derived neurotrophic factor (BDNF). Here we used gene therapy to increase or silence BDNF production in BMSCs to investigate the role of BDNF in BMSC-mediated neuroprotection. In a spinal cord organotypic culture, BMSC-conditioned medium significantly enhanced spinal motoneuron survival by 64% compared with culture medium only. Only conditioned medium of BDNF-hypersecreting BMSCs sustained this neuroprotective effect. In a rat model of spinal cord contusion, a BDNF-dependent neuroprotective effect was confirmed; only with a subacute transplant of BDNFhypersecreting BMSCs were significantly more spared motoneurons found at 4 weeks postinjury compared with vehicle controls. Spared nervous tissue volume was improved by 68% with both control BMSCs and BDNF-hypersecreting BMSCs. In addition, blood vessel density in the contusion with BDNF-hypersecreting BMSCs was 35% higher compared with BMSC controls and sixfold higher compared with vehicle controls. BDNF-silenced BMSCs did not survive the first week of transplantation, and no neuroprotective effect was found at 4 weeks after transplantation. Together, our data broaden our understanding of the role of BDNF in BMSC-mediated neuroprotection and successfully exploit BDNF dependency to enhance anatomical spinal cord repair.

Original languageEnglish (US)
Pages (from-to)2209-2220
Number of pages12
JournalCell transplantation
Issue number11
StatePublished - 2015
Externally publishedYes


  • Blood vessels
  • Bone marrow stromal cells (BMSCs)
  • Brain-derived neurotrophic factor (BDNF)
  • Gene therapy
  • Neuroprotection
  • Spinal cord injury

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation


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