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Periodontal tissue regeneration by transplantation of own bone marrow mesenchymal stem cells

自体骨髓间充质干细胞移植牙周组织再生

基本信息

批准号：
15390647
负责人：
KAWAGUCHI Hiroyuki
金额：
$ 9.09万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

To elucidate the performance of mesenchymal stem cells (MSCs) after transplantation, green fluorescent protein (GFP)-transduced MSCs were cultured and mixed with Atelocollagen at final concentration of 2x10^7 cells/ml and were auto-transplanted into experimental class III defects in the dogs. One month after GFP-transduced MSCs transplantation, immunohistochemical results showed that GFP-positive cells were present in the whole area of the defects. Cementoblasts arranged along the denuded surface, osteoblasts and osteocytes of regenerated bone, and fibroblasts of the regenerated periodontal ligament were GFP-positive. These findings suggested that some transplanted MSCs survive, differentiate into periodontal tissue cells and release various kind of cytokines, all of which promote periodontal tissue regeneration.Another animal study, MSCs transplantation in chronic periodontal defects model, class III defects with inflammation in beagle dogs, showed much better results concerning cementum regeneration than control. 2 weeks after MSCs transplantation, although bone regeneration was not formed yet, almost all denuded root surface was osteopontin (OPN) positive. Adjacent to the root surface, oval shaped like cells were arranged along the surface. Epithelial cell invasion was not observed. On the other hand, in control group, immunoreaction was not observed on root surface. Epithelial tissue invaded into the top of furcation area. These findings indicated that transplantation of MSCs near the root surface might differentiate into cementblasts at early stage and enhance new cementum formation.These animal studies demonstrated the therapeutic potential of bone marrow MSCs transplantation for periodontal tissue regeneration.

为了阐明移植后间充质干细胞（MSC）的性能，培养绿色荧光蛋白（GFP）转导的MSC，并将其与终浓度为2 × 10^7个细胞/ml的Atelocollagen混合，并自体移植到狗的实验III类缺损中。移植后1个月，免疫组化结果显示GFP阳性细胞存在于整个缺损区域。成牙骨质细胞沿着裸露表面排列，再生骨的成骨细胞和骨细胞，再生牙周膜的成纤维细胞呈GFP阳性。这些结果表明，部分移植的MSCs存活，分化为牙周组织细胞，并释放各种细胞因子，所有这些都促进牙周组织再生。另一项动物研究，MSCs移植在慢性牙周缺损模型，III类缺损伴炎症的beagle犬中，显示出比对照组更好的牙骨质再生效果。骨髓间充质干细胞移植后2周，虽然尚未形成骨再生，但几乎所有裸露的牙根面骨桥蛋白（OPN）均呈阳性。在根面附近，沿根面沿着有椭圆形细胞。未观察到上皮细胞浸润。对照组牙根面未见免疫反应。上皮组织侵入根分叉区顶部。这些结果表明，骨髓间充质干细胞移植到牙周组织再生的动物实验表明，骨髓间充质干细胞移植的牙周组织再生的治疗潜力，可以在早期分化为成牙骨质细胞，促进新牙骨质的形成。