Transplanted Bone Marrow Stromal Cells Promote Axonal Regeneration and Improve Motor Function in a Rat Spinal Cord Injury Model

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

doi:10.1227/01.neu.0000341905.57162.1d

Cited by 44 publications

(38 citation statements)

References 52 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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“…More importantly, they have no tumorigenesis [19,20]. Following transplantation, they extensively migrate towards the injured CNS tissue, expressed the phenotypes of neural cells, and produce several neuroprotective factors [12,[21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Biological Features of Human Bone Marrow Stromal Cells (hBMSC) Cultured with Animal Protein-Free Medium—Safety and Efficacy of Clinical Use for Neurotransplantation

Shichinohe

Kuroda

Sugiyama

et al. 2011

Transl. Stroke Res.

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The donor cell culture in animal serum-free medium is quite important for the clinical application of cell transplantation therapy. This study was aimed to test the hypothesis that the human bone marrow stromal cells (hBMSC) expanded with fetal calf serum (FCS)-free, platelet lysate (PL)-containing medium retain their biological features favoring central nervous system regeneration. The hBMSC were cultured with 5% PL or 10% FCS. Their phenotypes were analyzed with flow cytometry, and their production of growth factors was quantified with enzyme-linked immunosorbent assay. Their capacity of neural differentiation was verified by immunocytochemistry. There was no significant difference in morphology and cell surface marker between the hBMSC-FCS and hBMSC-PL. Both of them were positive for CD44, CD90, CD105, and CD166 and were negative for CD34, CD45, and CD271. The production of human brain-derived neurotrophic factor, human hepatocyte growth factor, human β-nerve growth factor, and human platelet-derived growth factor-BB did not differ between the two groups, although the hBMSC-PL produced significantly more amount of TGF-β1 than the hBMSC-FCS. There was no significant difference in their in vitro differentiation into the neurons and astrocytes between the two groups. The hBMSC expanded with PL-containing medium retain their biological capacity of neural differentiation and neuroprotection. The PL may be a clinically valuable and safe substitute for FCS in expanding the hBMSC for cell therapy.

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“…Specific characteristics of MSCs include ease of isolation, extensive proliferative potential and ability to differentiate into various cell types, making them an attractive resource for applications in regenerative medicine [1,2,3]. MSC-based cell therapy has shown great significance in treating a broad spectrum of diseases, including ocular surface diseases [4,5,6,7,8].…”

Section: Introductionmentioning

confidence: 99%

Effects of Bone Marrow Mesenchymal Stem Cells on Cell Proliferation and Growth Factor Expression of Limbal Epithelial Cells in vitro

Zhang

et al. 2012

Ophthalmic Res

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Mesenchymal stem cells (MSCs) can play an active role in the reconstruction of the ocular surface; however, the mechanisms by which the implanted MSCs exert their effects remain elusive. In the present study, we investigated the influences of MSCs on cell proliferation and growth factor expression of corneal limbal epithelial cells (LECs) in vitro. Rat LECs were either cocultured with rat MSCs or cultured in rat MSC-conditioned medium. The harvested LECs were subjected to light microscopy, MTT assay, bromodeoxyuridine (BrdU) staining, flow cytometry and real-time quantitative RT-PCR analysis, respectively. Light microscopy showed that coculturing of LECs with MSCs significantly increased the proliferation of LECs. The MTT assay showed that MSC-conditioned medium significantly increased the cell viability of LECs compared to those incubated with plain medium. BrdU immunostaining and flow-cytometric analysis of the cell cycle showed that the cell proliferation rate of LECs cocultured with MSCs was significantly higher than that of LECs cultured alone. Real-time quantitative RT-PCR analysis showed that expression of epidermal growth factor in LECs cocultured with MSCs was significantly higher than that in LECs cultured alone. However, expression of basic fibroblast growth factor showed no difference under the two culture conditions. These results indicate that MSCs promote the survival and proliferation of LECs, and these effects may be mediated in a paracrine manner.

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Transplanted Bone Marrow Stromal Cells Promote Axonal Regeneration and Improve Motor Function in a Rat Spinal Cord Injury Model

Abstract: The findings suggest that the transplanted BMSCs acquire neural cell phenotypes around the injury site and contribute to rebuild the neural circuits, including the corticospinal tract, promoting functional recovery of the hind limbs.

Cited by 44 publications

References 52 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

Biological Features of Human Bone Marrow Stromal Cells (hBMSC) Cultured with Animal Protein-Free Medium—Safety and Efficacy of Clinical Use for Neurotransplantation

Effects of Bone Marrow Mesenchymal Stem Cells on Cell Proliferation and Growth Factor Expression of Limbal Epithelial Cells in vitro

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