Regulation of mesenchymal cell differentiation and biological cartilage repair using cell supplementation

使用细胞补充剂调节间充质细胞分化和生物软骨修复

• 批准号: 17390415
• 负责人: KIMURA Tomoatsu
• 金额: $ 10.35万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390415/
• 关键词: differentiation; chondrocyte; cartilage; repair; 変性; 滑膜

We have identified BMP signal related factor, SF3b4, and also Gas6. These factors regulated chondrogenic differentiation of undifferentiated mesenchymal cells. We, then analyzed the effect of differentiation-regulated mesenchymal cells on the degenerated cartilage in vitro and demonstrated that the cells could attach and embedded into surface matrix. To further extend the cell-based therapy to the cartilage repair, we have attempted scaffold-free transplantation of large numbers of chondrocytic cells ; cell supplementation by intra-articular injection. A full-thickness articular cartilage defect was created in the femoral patellar groove of the nude rat. N1511 cells with undifferentiated chondroprogenitor phenotype were used for cell supplementation. N1511 cells were treated with bone morphogenetic protein (BMP)/insulin to induce chondrogenic differentiation. Undifferentiated N1511 cells or BMP/insulin treated chondrocytic N1511 cells were briefly labeled with fluorescent dye and a aliquot of 1x107/ml of cells was injected into the knees. Localization of the injected cells and the repair of the defect were evaluated histologically by 18 weeks. Injected cells were mostly attached to the synovial surface and then engrafted into sub-synovial tissue. The cells were also scattered among the repaired tissue that filled the osteochondral defect, whereas they were not detected on the surface of normal articular cartilage. There was no histological evidence of synovial inflammation or ectopic chondroplasia. Spontaneous hyaline regeneration of the defect was not observed in the controls without cell injection. However, intra-articular cell injection enhanced the repair of the defect and BMP/insulin-treated chondrocytic N1511 cells showed better cartilage repair than undifferentiated N1511 cells. Thus, intra-articular supplementation of committed chondrocytic cells may be a potential cell-based therapy for articular cartilage lesions.

我们已经鉴定出BMP信号相关因子SF 3b 4和Gas 6。这些因子调节未分化间充质细胞的软骨分化。然后，我们分析了分化调节的间充质细胞对体外退变软骨的作用，证明了细胞可以附着并嵌入表面基质。为了进一步将基于细胞的治疗扩展到软骨修复，我们尝试了大量软骨细胞的无支架移植;通过关节内注射补充细胞。在裸大鼠股骨髌骨沟内造成全层关节软骨缺损。具有未分化软骨祖细胞表型的N1511细胞用于细胞补充。用骨形态发生蛋白（BMP）/胰岛素处理N1511细胞以诱导成软骨分化。用荧光染料简单标记未分化的N1511细胞或BMP/胰岛素处理的软骨细胞N1511细胞，并将1 × 107/ml细胞的等分试样注射到膝盖中。18周时对注射细胞的定位和缺损的修复进行组织学评价。注射的细胞主要附着在滑膜表面，然后植入滑膜下组织。这些细胞也分散在填充骨软骨缺损的修复组织中，而在正常关节软骨表面没有检测到。没有滑膜炎症或异位软骨形成的组织学证据。在未注射细胞的对照组中未观察到缺损的自发性透明再生。然而，关节内细胞注射增强了缺损的修复，BMP/胰岛素处理的软骨细胞N1511细胞比未分化的N1511细胞表现出更好的软骨修复。因此，关节内补充定向软骨细胞可能是一种潜在的基于细胞的治疗关节软骨病变。

项目成果

PDGF receptor β is a potent regulator of mesenchymal stromal cell function

• DOI: 10.1359/jbmr.080409
• 发表时间: 2008-09-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Tokunaga, Ayano;Oya, Takeshi;Sasahara, Masakiyo
• 通讯作者: Sasahara, Masakiyo

Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells

• DOI: 10.1093/rheumatology/ken003
• 发表时间: 2008-04-01
• 期刊: RHEUMATOLOGY
• 影响因子: 5.5
• 作者: Nakamura, C.;Matsushita, I.;Kimura, T.
• 通讯作者: Kimura, T.

Expression of GAS6 and AXL in developing embryo limbs.

GAS6 和 AXL 在发育中的胚胎肢体中的表达。

• 发表时间: 2008
• 作者: Seki S;et al.;Motomura H.
• 通讯作者: Motomura H.

Molecular mechanism of apoptosis and gene expressions in human lymphoma U937 cells treated with anisomycin.

• DOI: 10.1016/j.cbi.2007.12.003
• 发表时间: 2008-03
• 期刊: Chemico-biological interactions
• 影响因子: 5.1
• 作者: Takeshi Hori;T. Kondo;Y. Tabuchi;I. Takasaki;Qing‐Li Zhao;M. Kanamori;T. Yasuda;Tomoatsu Kimura

Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis.

• DOI: 10.1007/s10165-006-0522-2
• 发表时间: 2006-01-01
• 期刊: Modern rheumatology
• 影响因子: 2.2
• 作者: Matsushita, Isao;Uzuki, Miwa;Kimura, Tomoastu
• 通讯作者: Kimura, Tomoastu