Synergistic effects of bone marrow stromal cells and a Rho kinase (ROCK) inhibitor, Fasudil on axon regeneration in rat spinal cord injury

Chiba, Yasuhiro; Kuroda, Satoshi; Shichinohe, Hideo; Hokari, Masaaki; Osanai, Toshiya; Maruichi, Katsuhiko; Yano, Shunsuke; Hida, Kazutoshi; Iwasaki, Yoshinobu

doi:10.1111/j.1440-1789.2009.01077.x

Cited by 41 publications

(28 citation statements)

References 48 publications

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“…Furthermore, the BMSC markedly induce neurite extension from the motor neurons when transplanted onto the spinal cord slice [34] . The BMSC enhance the regeneration of the descending corticospinal tract and promote the recovery of motor function when directly transplanted into the injured spinal cord of rats [35,36] . The mechanisms through which the engrafted BMSC ameliorate the damaged CNS tissue and enhance functional recovery are still obscure.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Stromal Cell Transplantation Attenuates Cognitive Dysfunction due to Chronic Cerebral Ischemia in Rats

Shichinohe

Kuroda²,

Sugiyama³

et al. 2010

Dement Geriatr Cogn Disord

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Aims: This study was aimed to elucidate if bone marrow stromal cells (BMSC) could ameliorate cognitive dysfunction due to chronic cerebral ischemia when transplanted into the brain. Methods: The BMSC were harvested from green fluorescence protein (GFP)-expressing mice. Wistar rats were subjected to bilateral common carotid artery (CCA) ligation. The BMSC (4 × 10⁵ cells) or vehicle were stereotactically injected into the right striatum 24 h after the insult. Cognitive function was evaluated with the Morris water maze task after 3 and 5 weeks. Histological analysis was performed after 6 weeks. Results: Cognitive function was significantly impaired in the vehicle-transplanted animals, when compared with the non-CCA-ligation animals. BMSC transplantation significantly improved it. The BMSC were widely distributed in the ischemic brain, including the neocortex, white matter and hippocampus, and some of them expressed the phenotypes of neurons, astrocytes and endothelium. They also significantly ameliorated white matter damage. Conclusions: These findings strongly suggest that the BMSC may have the potential to attenuate white matter injury and improve cognitive dysfunction due to chronic cerebral ischemia. The present results would shed light on the potential of a novel strategy, cell therapy against ischemia-related cognitive dysfunction.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow Stromal Cell Transplantation Attenuates Cognitive Dysfunction due to Chronic Cerebral Ischemia in Rats

Shichinohe

Kuroda²,

Sugiyama³

et al. 2010

Dement Geriatr Cogn Disord

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“…Several studies have reported that BMSCs have indirect neuroprotective effects due to secretion of neurotrophic or growth factors, including basic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and insulin-like growth factor 1 [6, 11]. A recent study reported that BDNF and GDNF induce extensive axonal sprouting in the injured CNS [11].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, spinal cord regenerative therapy using BMSCs has begun to be clinically applied, leading to positive results in human and veterinary medicine [1, 23, 26]. Transplanted BMSCs are believed to exert their effects by producing neurotrophins or by contacting host spinal tissues [6]. Other researchers, however, have shown only modest or inconsistent recovery [9], and transplantation does not improve repair or recovery in rats with thoracic contusion injuries [32].…”

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confidence: 99%

Effects of Polyethylene Glycol Administration and Bone Marrow Stromal Cell Transplantation Therapy in Spinal Cord Injury Mice

Oda

Tani

Isozaki

et al. 2014

The Journal of Veterinary Medical Science

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Bone marrow stromal cell (BMSC) transplantation has been reported as treatments that promote functional recovery after spinal cord injury (SCI) in humans and animals. Polyethylene glycol (PEG) has been also reported as treatments that promote functional recovery after spinal cord injury (SCI) in humans and animals. Therefore, administration of PEG combined with BMSC transplantation may improve outcomes compared with BMSC transplantation only in SCI model mice. SCI mice were divided into a control-group, BMSC-group, PEG-group and BMSC+PEG-group. BMSC transplantation and PEG administration were performed immediately after surgery. Compared to the control-group, PEG- and BMSC+PEG-groups showed significant locomotor functional recovery 4 weeks after therapy. We observed no significant differences among the groups. In the BMSC- and BMSC+PEG-groups, immunohistochemistry showed that many neuronal cells aggressively migrated toward the glial scar from the region rostral of the lesion site. In the control- and PEG-groups, the boundary of the injured regions was covered with astrocytes, and a few neuronal cells were migrated toward the glial scar. We conclude that combined BMSC transplantation with PEG treatment showed no synergistic effects on locomotor functional recovery or beneficial cellular events. Further studies may improve the effect of the treatment, including modification of the timing of BMSC transplantation.

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“…In fact, we have confirmed that the BMSC significantly improve motor function on rotarod test, when stereotactically injected into the ipsilateral striatum at 7 days after the onset of permanent middle cerebral artery (MCA) occlusion 12, 38, 39 . The BMSC also promote functional recovery of the lower extremities, when directly transplanted into the injured spinal cord at 7 days after the onset of SCI 6, 7, 15, 40 . More interestingly, the BMSC have the potential to ameliorate cognitive dysfunction under certain conditions.…”

Section: Recent Progress In Bmsc Transplantationmentioning

confidence: 99%

Bone Marrow Stromal Cell Transplantation for Central Nervous System Disorders: Perspectives for Translational Research and Clinical Application

Kuroda¹,

Kuge²,

Tamaki³

et al. 2010

Molecular Imaging for Integrated Medical Therapy and Drug Development

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There is increasing evidence that the transplanted BMSC significantly promote functional recovery after CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, traumatic brain injury and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with CNS disorders. In this review, therefore, we discuss what we should clarify to establish cell transplantation therapy as the scientifically proven entity in clinical situation and describe our recent works for this purpose. The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. The BMSC can be expanded in vitro using the animal serum-free medium. Pharmacological modulation may accelerate the in vitro proliferation of the BMSC. Using in vivo optical imaging technique, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future.

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Synergistic effects of bone marrow stromal cells and a Rho kinase (ROCK) inhibitor, Fasudil on axon regeneration in rat spinal cord injury

Cited by 41 publications

References 48 publications

Bone Marrow Stromal Cell Transplantation Attenuates Cognitive Dysfunction due to Chronic Cerebral Ischemia in Rats

Bone Marrow Stromal Cell Transplantation Attenuates Cognitive Dysfunction due to Chronic Cerebral Ischemia in Rats

Effects of Polyethylene Glycol Administration and Bone Marrow Stromal Cell Transplantation Therapy in Spinal Cord Injury Mice

Bone Marrow Stromal Cell Transplantation for Central Nervous System Disorders: Perspectives for Translational Research and Clinical Application

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