Intravenous administration of mesenchymal stem cells derived from bone marrow after contusive spinal cord injury improves functional outcome

Osaka, Misuzu; Honmou, Osamu; Murakami, Tomohiro; Nonaka, Tadashi; Houkin, Kiyohiro; Hamada, Hirofumi; Kocsis, Jeffery D.

doi:10.1016/j.brainres.2010.05.011

Cited by 198 publications

(148 citation statements)

References 51 publications

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“…30,[51][52][53][54][55] Some of the beneficial effects of MSCs are mediated by their release of neurotrophic factors. 34,35 This allows neurotrophins to be delivered locally to the spinal cord, overcoming issues related to neurotrophin penetration and bioavailability.…”

Section: Beneficial Effects Of Mscsmentioning

confidence: 99%

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Gransee

Zhan

Sieck

et al. 2015

Journal of Neurotrauma

116

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Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are important in modulating neuroplasticity and promoting recovery after spinal cord injury. Intrathecal delivery of BDNF enhances functional recovery following unilateral spinal cord hemisection (SH) at C2, a well-established model of incomplete cervical spinal cord injury. We hypothesized that localized delivery of BDNF-expressing mesenchymal stem cells (BDNF-MSCs) would promote functional recovery of rhythmic diaphragm activity after SH. In adult rats, bilateral diaphragm electromyographic (EMG) activity was chronically monitored to determine evidence of complete SH at 3 days post-injury, and recovery of rhythmic ipsilateral diaphragm EMG activity over time post-SH. Wild-type, bone marrow-derived MSCs (WT-MSCs) or BDNF-MSCs (2 · 10 5 cells) were injected intraspinally at C2 at the time of injury. At 14 days post-SH, green fluorescent protein (GFP) immunoreactivity confirmed MSCs presence in the cervical spinal cord. Functional recovery in SH animals injected with WT-MSCs was not different from untreated SH controls (n = 10; overall, 20% at 7 days and 30% at 14 days). In contrast, functional recovery was observed in 29% and 100% of SH animals injected with BDNF-MSCs at 7 days and 14 days post-SH, respectively (n = 7). In BDNF-MSCs treated SH animals at 14 days, root-mean-squared EMG amplitude was 63 -16% of the pre-SH value compared with 12 -9% in the control/WT-MSCs group. We conclude that localized delivery of BDNF-expressing MSCs enhances functional recovery of diaphragm muscle activity following cervical spinal cord injury. MSCs can be used to facilitate localized delivery of trophic factors such as BDNF in order to promote neuroplasticity following spinal cord injury.

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Section: Beneficial Effects Of Mscsmentioning

confidence: 99%

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Gransee

Zhan

Sieck

et al. 2015

Journal of Neurotrauma

116

View full text Add to dashboard Cite

show abstract

“…BMSCs were isolated and identified as described previously (4,7). Briefly, primary BMSCs were harvested from tibias and femurs of 3-week-old Sprague-Dawley rats under aseptic conditions and then purified and passaged in dulbecco's modified eagle medium (DMEM, Gibco, St. Louis, MO, USA) supplemented with 10% fetal bovine serum (FBS, Gibco).…”

Section: Isolation Culture Identification and Differentiation Of Bmentioning

confidence: 99%

“…The systemic administration of BMSCs provides a therapeutic benefit in rats with a SCI (4). However, this treatment seems to have more limited therapeutic effectiveness than local direct injection because of the uneven distribution of BMSCs in vivo after intravenous injection (5).…”

Section: Introductionmentioning

confidence: 99%

“…Ninety-nine percent of intravenously injected MSCs adhere to the lungs, while only 2-3% of adhering MSCs are released into the circulation (6). Numerous experiments have shown that BMSCs will preferentially migrate to sites of inflammation after intravenous administration (4,(7)(8)(9). A way to promote the migration of exogenous BMSCs to the injury site has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Transplantation of bone marrow mesenchymal stem cells pretreated with valproic acid in rats with an acute spinal cord injury

Chen

Cui

et al. 2014

BST

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“…Nevertheless, there are no effective therapies for this condition, although many studies have attempted to find effective therapeutic alternatives. Therapy with mesenchymal stem cells (MSCs) is considered a promising option, because these cells are multipotent and can easily be isolated from adult individuals and expanded in vitro (Osaka et al, 2010;Zhukareva et al, 2010;Nakajima et al, 2012;Dariolli et al, 2013;Zhou et al, 2013;Kingham et al, 2014;Lin et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats

Rosado¹,

Carvalho²,

Alves³

et al. 2017

Genet. Mol. Res.

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Intravenous administration of mesenchymal stem cells derived from bone marrow after contusive spinal cord injury improves functional outcome

Cited by 198 publications

References 51 publications

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Transplantation of bone marrow mesenchymal stem cells pretreated with valproic acid in rats with an acute spinal cord injury

Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats

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