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Intranasal delivery of bone marrow stromal cells to spinal cord lesions

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  • Intranasal delivery of bone marrow stromal cells to spinal cord lesions

    J Neurosurg Spine. 2015 Apr 3:1-9. [Epub ahead of print]
    Intranasal delivery of bone marrow stromal cells to spinal cord lesions.
    Ninomiya K1, Iwatsuki K, Ohnishi YI, Ohkawa T, Yoshimine T.
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    OBJECT The intranasal delivery of bone marrow stromal cells (BMSCs) or mesenchymal stem cells to the injured brains of rodents has been previously reported. In this study, the authors investigated whether BMSCs migrate to spinal cord lesions through an intranasal route and whether the administration affected functional recovery. METHODS Forty Sprague-Dawley rats that were subjected to spinal cord injuries at the T7-8 level were divided into 5 groups (injured + intranasal BMSC-treated group, injured + intrathecal BMSC-treated group, injured-only group, injured + intranasal vehicle-treated group, and injured + intrathecal vehicle-treated group). The Basso-Beattie-Bresnahan (BBB) scale was used to assess hind limb motor functional recovery for 2 or 4 weeks. Intralesionally migrated BMSCs were examined histologically and counted at 2 and 4 weeks. To evaluate the neuroprotective and trophic effects of BMSCs, the relative volume of the lesion cavity was measured at 4 weeks. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in the CSF were evaluated at 2 weeks. RESULTS Intranasally administered BMSCs were confirmed within spinal cord sections at both 2 and 4 weeks. The highest number, which was detected in the intrathecal BMSC-treated group at 2 weeks, was significantly higher than that in all the other groups. The BBB score of the intranasal BMSC-treated group showed statistically significant improvements by 1 week compared with the control group. However, in the final BBB scores, there was a statistically significant difference only between the intrathecal BMSC-treated group and the control group. The cavity ratios in the BMSC-treated groups were smaller than those of the control groups, but the authors did not find any significant differences in the NGF and BDNF levels in the CSF among the treatment and control groups. CONCLUSIONS BMSCs reached the injured spinal cord through the intranasal route and contributed to the recovery of hind limb motor function and lesion cavity reduction. However, the effects were not as significant as those seen in the intrathecal BMSC-treated group.

    BBB = Basso-Beattie-Bresnahan; BDNF = brain-derived neurotrophic factor; BMSC = bone marrow stromal cell; DAPI = 4′,6-diamidino-2-phenylindole; DMEM = Dulbecco modified Eagle medium; EGFP = enhanced green fluorescent protein; MSC = mesenchymal stem cell; NGF = nerve growth factor; PBS = phosphate-buffered saline; SCI = spinal cord injury; SEM = standard error of the mean; bone marrow stromal cells; i.n. = intranasal; i.t. = intrathecal; intranasal delivery; spinal cord injury
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