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
BDNF-hypersecreting 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.