Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in the rat

Idé, Chizuka; Nakai, Yoshiyasu; Nakano, Norihiko; Seo, Tae-Beom; Yamada, Yoshihiro; Endo, Kaori; Noda, Tetsuji; Saito, Fukuki; Suzuki, Yoshihisa; Fukushima, Masanori; Nakatani, Toshio

doi:10.1016/j.brainres.2010.03.043

Cited by 111 publications

(91 citation statements)

References 51 publications

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“…Furthermore, a recent study examined the response of MSC to environmental stimuli in the injured spinal cord tissue, and found increased synthesis by these cells of various cytokines, including IL-6, IL-7, and VEGF (Zhukareva et al, 2010). Because MSC can alter their gene expression profile in response to the surrounding environment (Ide et al, 2010;Mosser and Edwards, 2011;Yamaguchi et al, 2006), we hypothesize that transplanted MSC do not differentiate into neural cells, at least in the injured spinal cord environment, but instead they bring about CNS functional recovery by modifying the SCI environment to directly affect the endogenous cells present in that territory.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury

Nakajima

Uchida²,

Guerrero³

et al. 2012

Journal of Neurotrauma

368

299

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Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0 · 10 6 PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-a and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1-or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS-or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.

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Section: Discussionmentioning

confidence: 99%

Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury

Nakajima

Uchida²,

Guerrero³

et al. 2012

Journal of Neurotrauma

368

299

View full text Add to dashboard Cite

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“…MSC is an appropriate candidate for bone regeneration (43). Although, clinical application of MSCs have shown beneficial effects in the treatment of various diseases, implanted MSCs do not survive for long after transplantation (44). Also, evidence has shown that allogeneic MSCs can elicit immune response against the transplanted cells and immunological issues present an obstacle for tissue engineering (45).…”

Section: Discussionmentioning

confidence: 99%

Adipose Derived Stem Cells Conditioned Media in Combination with Bioceramic-Collagen Scaffolds Improved Calvarial Bone Healing in Hypothyroid Rats

Sanchooli

Norouzian

Ardeshirylajimi

et al. 2017

Iran Red Crescent Med J

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Background: Tissue engineering is an available treatment for large bone defects. The therapeutic effects of mesenchymal stem cell (MSC) are mostly attributed to secretion of many cytokines and growth factors. Many factors of MSC secretions accumulate in a conditioned medium and these factors recruit native cells into a defect site to generate new bone tissues. Objectives: The aim of this study was to evaluate the influence of adipose tissue derived MSCs-conditioned medium (ADMSC-CM) on bone repair of rats with critical -size calvarial defect. Methods: This experimental study was performed at Shahid Beheshti University of Medical Sciences, Tehran, Iran, from 2016 to 2017. Conditioned medium was collected from healthy rat adipose tissue derived MSC (ADMSC) at passage four. Calvarial bone defect was created in hypothyroid rats using a dental bur. Sampling was taken by the linear-mono-gram method to determine sample size (n = 6 per group). The rats were divided randomly into four groups based on graft material as follows: empty defect, scaffold (Bio-Oss / type I collagen gel), scaffold / ADMSCs, scaffold /ADMSC-CM. Evaluations were made at 4 and 8 weeks after surgery using stereological analysis. Results: Histological analysis at 8 weeks indicated that the newly regenerated tissue almost covered the defect in the ADMSC-CM group. Stereological analysis showed that ADMSC-CM increased regenerated bone and numbers of osteocytes and osteoblasts compared with the defect and scaffold groups (P < 0.05). Also, bone regeneration was more effective in animals treated with ADMSC-CM than in those received ADMSC. Conclusions: These results suggest an important role for ADMSC-CM in bone regeneration, through trophic impact of its cytokines and growth factors that induce native cell proliferation and migration into the defect. Thus, ADMSC-CM seems to have good potential for application in bone tissue regeneration, in the cases of hypothyroidism.

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“…Axons found in the astrocyte-devoid tissue might be those that had grown following the injury. 18 It has been reported that exercise promotes tissue formation and axonal extension in lesions of SCI. 5,19 The severity of SCI is considered to be similar between the PP and DP groups, judging from Forced plantar placement training of hind paws in SCI rats M Hayashibe et al the BBB scores of 0.5 ± 0.3 and 0.4 ± 0.2 for PP and DP groups, respectively.…”

Section: Tissue Recovery and Axonal Extensionmentioning

confidence: 99%

Locomotor improvement of spinal cord-injured rats through treadmill training by forced plantar placement of hind paws

et al. 2015

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Study design: Experimental training model of rats with spinal cord injury (SCI).Setting: Osaka, Japan Objective: To investigate the effect of forced treadmill training by plantar placement (PP), as compared with dorsal placement (DP), of the dorsal paws on the locomotor behaviors of spinal cord-injured rats. Methods: The spinal cord was contusion-injured at the thoracic level. Rats were divided into three groups: forced training involving stepping by PP and DP and non-forced training/assistance (nT). Training began 1 week after injury and was conducted for 4 weeks. Locomotor behaviors were estimated using Basso-Beattie-Bresnahan (BBB) scores, dorsiflexion of the hind paws and footprints of the hind paws. Histological and immunohistochemical examinations of the spinal cord lesions were conducted after 4 weeks of training. Results: The values, respectively, of PP, DP and nT groups at 4 weeks of training were as follows: BBB scores were 15.6 ± 0.8, 7.7 ± 1.3 and 10.3 ± 0.4. The paw dorsiflexion angles were 34.1 ± 5.2, 16.4 ± 2.4 and 23.6 ± 3.0 degrees, respectively. The stride angles were 5.1 ± 0.9, 13.7 ± 4.9 and 17.8 ± 4.0 degrees for the left paws. Cavity volumes were 10.3 ± 2.1, 31.0 ± 2.0 and 28.2 ± 4.9%. In addition to cavities, there were astrocyte-devoid areas containing some loose tissues, through which many axons extended longitudinally. Conclusions: The BBB score, dorsiflexion angle and stride angle were consistently improved in the PP group. Cavity formation was more reduced, and many axons extended through coarse tissues formed in astrocyte-devoid areas at the lesion in the PP group. INTRODUCTIONSpinal cord injury (SCI) is devastating; patients with SCI lose functions below the level of the injury, and recovery of the locomotor functions is limited even with extensive rehabilitation. Body weight support treadmill (BWST) training with plantar stepping is widely used for locomotor exercises in the rehabilitation of patients with SCI. However, the effectiveness of plantar stepping of the hind feet has not been fully evaluated experimentally. The present study focused on the effect of forced treadmill training by plantar placement (PP) of the hind paws on the locomotor behaviors of rats with SCI. Recent cell transplantation studies have reported the recovery of injured spinal cord tissue and the behavioral improvement of SCI animals. 1 Our previous studies showed that bone marrow stromal cell transplantation is effective for locomotor recovery from SCI in rats, 2 findings that have been applied to clinical cases. 3 Along with the emergence of potentially effective treatments of SCI, including cell transplantation therapy, hope for the rehabilitation of patients with SCI has increased. It is now all the more important to experimentally explore the effects of rehabilitation on recovery from SCI.

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Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in the rat

Cited by 111 publications

References 51 publications

Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury

Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury

Adipose Derived Stem Cells Conditioned Media in Combination with Bioceramic-Collagen Scaffolds Improved Calvarial Bone Healing in Hypothyroid Rats

Locomotor improvement of spinal cord-injured rats through treadmill training by forced plantar placement of hind paws

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