Dataset Information

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model.

ABSTRACT: The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy.

SUBMITTER: Yamaguchi S

PROVIDER: S-EPMC4788414 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model.

Yamaguchi Shoki S Aoyama Tomoki T Ito Akira A Nagai Momoko M Iijima Hirotaka H Tajino Junichi J Zhang Xiangkai X Kiyan Wataru W Kuroki Hiroshi H

PloS one 20160311 3

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochond ...[more]

PMID: 26968036

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Project description:The field of orthopedics seeks effective, safer methods for evaluating articular cartilage regeneration. Despite various treatment innovations, non-invasive, contrast-free full quantitative assessments of hyaline articular cartilage's regenerative potential using compositional magnetic resonance (MR) sequences remain challenging. In this context, our aim was to investigate the effectiveness of different MR sequences for quantitative assessment of cartilage and to compare them with the current gold standard delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) measurements. We employed ex vivo imaging in a preclinical minipig model to assess knee cartilage regeneration. Standardized osteochondral defects were drilled in the proximal femur of the specimens (n=14), which were divided into four groups. Porcine collagen scaffolds seeded with autologous adipose-derived stromal cells (ASC), autologous bone marrow stromal cells (BMSC), and unseeded scaffolds (US) were implanted in femoral defects. Furthermore, there was a defect group which received no treatment. After 6 months, the specimens were examined using different compositional MR methods, including the gold standard dGEMRIC as well as T1, T2, T2*, and T1ρ techniques. The statistical evaluation involved comparing the defect region with the uninjured tibia and femur cartilage layers and all measurements were performed on a clinical 3T MR Scanner. In the untreated defect group, we observed significant differences in the defect region, with dGEMRIC values significantly lower (404.86±64.2 ms, P=0.018) and T2 times significantly higher (44.24±2.75 ms, P<0.001). Contrastingly, in all three treatment groups (ASC, BMSC, US), there were no significant differences among the three regions in the dGEMRIC sequence, suggesting successful cartilage regeneration. However, T1, T2*, and T1ρ sequences failed to detect such differences, highlighting their lower sensitivity for cartilage regeneration. As expected, dGEMRIC is well suited for monitoring cartilage regeneration. Interestingly, T2 imaging also proved to be a reliable cartilage imaging technique and thus offers a contrast agent-free alternative to the former gold standard for subsequent in vivo studies investigating the cartilage regeneration potential of different treatment modalities.

Project description:Background:Mesenchymal stem cells (MSCs) can be easily expanded without losing the ability of multilineage differentiation, including oesteogenic, chondrogenic and adipogenic differentiation. These characters make MSCs a promising cell resource for cartilage defect repair. MSCs could be recruited by inflammatory stimulation, then home to the injury tissues. However, its capacity of homing is extremely limited. Thus, it has become extremely necessary to develop an agent or a method, which can be used to enhance the efficiency of MSCs homing. This study investigates the effect of stearic acid methyl ester (SAME) on MSCs mobilisation and cartilage regeneration. Methods:MSCs were isolated from femurs of Sprague-Dawley (SD) rats. MTT assay was used to detect effect of SAME on viability of MSCs. Transwell assay and wound healing assay were used to detect effect of SAME on migration of MSCs. RNA-seq, quantitative real-time PCR and western blot were performed to analyze the expression of RNAs and proteins. Colony forming assay and flow cytometry were used to evaluate the effect of SAME on MSCs mobilisation in vivo. A rat cartilage defect model was created to evaluate the effect of SAME on cartilage regeneration. Results:We found that SAME could promote the migration of MSCs. Interestingly, we found SAME significantly increased the expression levels of Vav1 in MSCs. On the other hand, the enhanced migration ability of MSCs induced by SAME was retarded by Vav1 small interfering RNA (siRNA) and Rho-associated protein kinase 2 (ROCK2) inhibitor. In addition, we also checked the effect of SAME on mobilisation of MSCs in vivo. The results showed that SAME increased the number of MSCs in peripheral blood and enhanced the capacity of colony formation. Finally, using a cartilage defect model in rats, we found SAME could improve cartilage repair. Conclusion:Our study demonstrates that SAME can enhance MSCs migration ability mainly through the Vav1/ROCK2 signaling pathway, which could contribute to the accelerated cartilage regeneration. The translational potential of this article:These findings provide evidence that SAME could be used as a therapeutic reagent for MSCs mobilisation and cartilage regeneration.

Dataset Information

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model.

Publications

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model.

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