Dataset Information

Intravenous injection of adult human bone marrow mesenchymal stromal cells attenuates spinal cord ischemia/reperfusion injury in a murine aortic arch crossclamping model.

ABSTRACT:

Objective

We sought to investigate the efficacy of human bone marrow mesenchymal stem/stromal cell (hBM-MSC) in a murine spinal cord ischemia/reperfusion (SCIR) model.

Methods

C57BL/6J mice were subjected to SCIR by crossclamping the aortic arch and left subclavian artery for 5.5 minutes. Two hours after reperfusion, hBM-MSCs (hBM-MSC group) or phosphate-buffered saline (control group) were intravenously injected without immunosuppressant. Hindlimb motor function was assessed until day 28 after reperfusion using the Basso Mouse Scale (BMS). The lumbar spinal cord was harvested at hour 24 and day 28, and the histologic number of NeuN-positive motor neurons in 3 cross-sections of each lumbar spinal cord and the gene expression were evaluated.

Results

BMS score was 0 throughout the study period in all control mice. BMS score was significantly greater in the hBM-MSC group than the control group from hour 8 (P < .05) to day 28 (P < .01). The numbers of motor neurons at hour 24 (P < .01) and day 28 (P < .05) were significantly preserved in the hBM-MSC group than the control group. mRNA expression levels of proinflammatory cytokines were significantly lower (P < .05), and those of insulin-like growth factor-1 (P < .01) and proangiogenic factors (P < .05) were significantly greater in the hBM-MSC group than the control group at hour 24.

Conclusions

hBM-MSC therapy may attenuate SCIR injury by preserving motor neurons, at least in part, through inhibition of proinflammatory cytokines and upregulation of proangiogenic factors in the reperfusion-injured spinal cord.

SUBMITTER: Nakai H

PROVIDER: S-EPMC9390396 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Intravenous injection of adult human bone marrow mesenchymal stromal cells attenuates spinal cord ischemia/reperfusion injury in a murine aortic arch crossclamping model.

Nakai Hidekazu H Fujita Yasuyuki Y Masuda Satoru S Komatsu Miki M Tani Ayumi A Okita Yutaka Y Okada Kenji K Kawamoto Atsuhiko A

JTCVS open 20210609

<h4>Objective</h4>We sought to investigate the efficacy of human bone marrow mesenchymal stem/stromal cell (hBM-MSC) in a murine spinal cord ischemia/reperfusion (SCIR) model.<h4>Methods</h4>C57BL/6J mice were subjected to SCIR by crossclamping the aortic arch and left subclavian artery for 5.5 minutes. Two hours after reperfusion, hBM-MSCs (hBM-MSC group) or phosphate-buffered saline (control group) were intravenously injected without immunosuppressant. Hindlimb motor function was assessed unti ...[more]

PMID: 36003746

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Project description:Purpose To evaluate whether noninvasive molecular imaging technologies targeting myeloperoxidase (MPO) can reveal early inflammation associated with spinal cord injury after thoracic aortic ischemia-reperfusion (TAR) in mice. Materials and Methods The study was approved by the institutional animal care and use committee. C57BL6 mice that were 8-10 weeks old underwent TAR (n = 55) or sham (n = 26) surgery. Magnetic resonance (MR) imaging (n = 6) or single photon emission computed tomography (SPECT)/computed tomography (CT) (n = 15) studies targeting MPO activity were performed after intravenous injection of MPO sensors (bis-5-hydroxytryptamide-tetraazacyclododecane [HT]-diethyneletriaminepentaacetic acid [DTPA]-gadolinium or indium 111-bis-5-HT-DTPA, respectively). Immunohistochemistry and flow cytometry were used to identify myeloid cells and neuronal loss. Proinflammatory cytokines, keratinocyte chemoattractant (KC), and interleukin 6 (IL-6) were measured with enzyme-linked immunosorbent assay. Statistical analyses were performed by using nonparametric tests and the Pearson correlation coefficient. P < .05 was considered to indicate a significant difference. Results Myeloid cells infiltrated into the injured cord at 6 and 24 hours after TAR. MR imaging confirmed the presence of ischemic lesions associated with mild MPO-mediated enhancement in the thoracolumbar spine at 24 hours compared with the sham procedure. SPECT/CT imaging of MPO activity showed marked MPO-sensor retention at 6 hours (P = .003) that continued to increase at 24 hours after TAR (P = .0001). The number of motor neurons decreased substantially at 24 hours after TAR (P < .01), which correlated inversely with in vivo inflammatory changes detected at molecular imaging (r = 0.64, P = .0099). MPO was primarily secreted by neutrophils, followed by lymphocyte antigen 6 complexhigh monocytes and/or macrophages. There were corresponding increased levels of proinflammatory cytokines KC (P = .0001) and IL-6 (P = .0001) that mirrored changes in MPO activity. Conclusion MPO is a suitable imaging biomarker for identifying and tracking inflammatory damage in the spinal cord after TAR in a mouse model. © RSNA, 2016 Online supplemental material is available for this article.

Project description:Neuroinflammation is one of the major causes of damage of the central nervous system (CNS) and plays a vital role in the pathogenesis of cerebral ischemia, which can result in long-term disability and neuronal death. Danhong injection (DHI), a traditional Chinese medicine injection, has been applied to the clinical treatment of cerebral stoke for many years. In this study, we investigated the protective effects of DHI on cerebral ischemia-reperfusion injury (CIRI) in rats and explored its potential anti-neuroinflammatory properties. CIRI in adult male SD rats was induced by middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. Results showed that DHI (0.5, 1, and 2 ml/kg) dose-dependently improved the neurological deficits and alleviated cerebral infarct volume and histopathological damage of the cerebral cortex caused by CIRI. Moreover, DHI (0.5, 1, and 2 ml/kg) inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular cell adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in ischemic brains, downregulated TNF-α, IL-1β, and monocyte chemotactic protein-1 (MCP-1) levels in serum, and reduced the neutrophil infiltration (myeloperoxidase, MPO) in ischemic brains, in a dose-dependent manner. Immunohistochemical staining results also revealed that DHI dose-dependently diminished the protein expressions of ICAM-1 and COX-2, and suppressed the activation of microglia (ionized calcium-binding adapter molecule 1, Iba-1) and astrocyte (glial fibrillary acidic protein, GFAP) in the cerebral cortex. Western blot analysis showed that DHI significantly downregulated the phosphorylation levels of the proteins in nuclear factor κB (NF-κB) and mitogen-activated protein kinas (MAPK) signaling pathways in ischemic brains. These results indicate that DHI exerts anti-neuroinflammatory effects against CIRI, which contribute to the amelioration of CNS damage.

Dataset Information

Intravenous injection of adult human bone marrow mesenchymal stromal cells attenuates spinal cord ischemia/reperfusion injury in a murine aortic arch crossclamping model.

Objective

Methods

Results

Conclusions

Publications

Intravenous injection of adult human bone marrow mesenchymal stromal cells attenuates spinal cord ischemia/reperfusion injury in a murine aortic arch crossclamping model.

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