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Role and Potential of Tissue Mesenchymal Stem cells on joint cartilage repair in dogs

组织间充质干细胞在犬关节软骨修复中的作用和潜力

基本信息

批准号：
18580315
负责人：
OKUMURA Masahiro
金额：
$ 2.45万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18580315/
关键词：
Veterinary Medicine Reconstructive Medicine cell Tissue Veterinary Orthopedics

项目摘要

The bone marrow harbors a population of mesenchymal stem cells (MSCs) that possess the potential to differentiate into bone, cartilage, fat and along other tissue pathways. MSCs from various species have been studied, and all of them demonstrated some specific characteristics. Despite the canine experimental model being widely used in experiments in vivo and in vitro, only a limited amount of information regarding canine MSCs is available. MSCs to undergo chondrogenic differentiation, factors that support strong cell to cell interaction (pellet culture system), growth factors (transforming growth factor beta), and an environment that maintains spherical morphology (polymer and collagen typew II gels) are considered to be necessary. For this reasons the main objective of this study was to introduce new animal experimental models in stem cell research and by using this model to contribute in understanding the influence of differentiate factors on MSC chondrogenic differentiation.The firs … More t half of this study showed that: i) cells from bone mallow stroma have potential for extensive proliferation and multilineage differentiation, refereeing them as MSCs; ii) MSCs cultured in pellet culture system demonstrated specific species character to undergo spontaneous chondrogenic differentiation without any external added bioactive stimulators; iii) collagen type II, which is physiological component of articular cartilage has potential to induce and maintain, and prior interation with TGF-betal dramatically to increase MSC chondrogenesis. These results would contribute for establishing new animal model for stem cell research, in understanding of growth factors, cluture system and ECM influence on MSC chondrogenesis, and finally in demonstration that bovine MSCs undergo chondrogenic differentiation probably under unique mechanism.The second half of this research was done for investigating environment of joint space under arthritic condition for MSCs to be applied. Here we concentrated to show synovial and chondrocytic reaction to exogenous hyaluronic acid. This pat of our study showed that: I) the expression of canine CD44 gene was demonstrated in both synovial cells and chondrocytes in vitro.; ii) the expression of canine hyaluronic acid synthase (HAS) genes was demonstrated in both synovial cells and chondrocytes in vitro; and iii) different expression of HAS genes in vitro under experimental inflammatory conditions was investigated. The results from this part of study suggested that exogenous hyaluronic acid induced activation of canine HAS-2 gene in canine synovial cells and chondrocytes, leading to the synthesis of high molecular weight hyaluronic acid, might explain inhibitory effects of hyaluronic acid on inflammation. Less

骨髓含有间充质干细胞（MSC）群体，其具有分化成骨、软骨、脂肪和沿着其他组织途径的潜力。已经研究了来自不同物种的MSC，并且它们都表现出一些特定的特性。尽管犬实验模型被广泛用于体内和体外实验，但关于犬MSC的信息有限。MSC经历软骨形成分化、支持强细胞与细胞相互作用的因子（沉淀培养系统）、生长因子（转化生长因子β）和维持球形形态的环境（聚合物和II型胶原凝胶）被认为是必要的。为此，本研究的主要目的是在干细胞研究中引入新的动物实验模型，并通过使用该模型来帮助理解分化因素对MSC软骨分化的影响。 ...更多信息结果表明：（1）来源于锦葵间质的细胞具有广泛的增殖和多向分化潜能，可称为间充质干细胞（MSCs）：（2）MSCs在细胞团培养系统中培养，显示出独特的种属特性，可在无任何外源性生物活性刺激物的情况下自发向软骨细胞分化; iii）II型胶原蛋白，其是关节软骨的生理组分，具有诱导和维持的潜力，并且在与TGF-β 1相互作用之前显著增加MSC软骨形成。这些结果将有助于建立新的干细胞研究动物模型，了解生长因子、培养体系和细胞外基质对间充质干细胞成软骨的影响，最终证明牛间充质干细胞可能通过独特的机制向软骨细胞分化。在这里，我们集中展示了滑膜和软骨细胞对外源性透明质酸的反应。本研究结果表明：1）体外培养的犬滑膜细胞和软骨细胞均表达CD 44基因。ii）在体外证实了犬透明质酸合酶（HAS）基因在滑膜细胞和软骨细胞中的表达;和iii）研究了HAS基因在体外实验性炎症条件下的不同表达。本部分研究结果提示，外源性透明质酸诱导犬滑膜细胞和软骨细胞中HAS-2基因活化，导致高分子量透明质酸的合成，这可能是透明质酸抑制炎症反应的机制之一。少