Seo Byoung-Moo, Miura Masako, Gronthos Stan, Bartold Peter Mark, Batouli Sara, Brahim Jaime, Young Marian, Robey Pamela Gehron, Wang Cun-Yu, Shi Songtao
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Lancet. 2004;364(9429):149-55. doi: 10.1016/S0140-6736(04)16627-0.
Periodontal diseases that lead to the destruction of periodontal tissues--including periodontal ligament (PDL), cementum, and bone--are a major cause of tooth loss in adults and are a substantial public-health burden worldwide. PDL is a specialised connective tissue that connects cementum and alveolar bone to maintain and support teeth in situ and preserve tissue homoeostasis. We investigated the notion that human PDL contains stem cells that could be used to regenerate periodontal tissue.
PDL tissue was obtained from 25 surgically extracted human third molars and used to isolate PDL stem cells (PDLSCs) by single-colony selection and magnetic activated cell sorting. Immunohistochemical staining, RT-PCR, and northern and western blot analyses were used to identify putative stem-cell markers. Human PDLSCs were transplanted into immunocompromised mice (n=12) and rats (n=6) to assess capacity for tissue regeneration and periodontal repair. Findings PDLSCs expressed the mesenchymal stem-cell markers STRO-1 and CD146/MUC18. Under defined culture conditions, PDLSCs differentiated into cementoblast-like cells, adipocytes, and collagen-forming cells. When transplanted into immunocompromised rodents, PDLSCs showed the capacity to generate a cementum/PDL-like structure and contribute to periodontal tissue repair.
Our findings suggest that PDL contains stem cells that have the potential to generate cementum/PDL-like tissue in vivo. Transplantation of these cells, which can be obtained from an easily accessible tissue resource and expanded ex vivo, might hold promise as a therapeutic approach for reconstruction of tissues destroyed by periodontal diseases.
导致牙周组织（包括牙周韧带、牙骨质和牙槽骨）破坏的牙周疾病是成年人牙齿缺失的主要原因，也是全球一项重大的公共卫生负担。牙周韧带是一种特殊的结缔组织，连接牙骨质和牙槽骨，以维持和原位支持牙齿，并保持组织内稳态。我们研究了人牙周韧带含有可用于再生牙周组织的干细胞这一观点。
从25颗手术拔除的人类第三磨牙获取牙周韧带组织，通过单克隆选择和磁激活细胞分选来分离牙周韧带干细胞（PDLSCs）。采用免疫组织化学染色、逆转录聚合酶链反应（RT-PCR）以及Northern和Western印迹分析来鉴定假定的干细胞标志物。将人牙周韧带干细胞移植到免疫缺陷小鼠（n = 12）和大鼠（n = 6）体内，以评估其组织再生和牙周修复能力。结果牙周韧带干细胞表达间充质干细胞标志物STRO-1和CD146/MUC18。在特定培养条件下，牙周韧带干细胞分化为成牙骨质细胞样细胞、脂肪细胞和胶原形成细胞。当移植到免疫缺陷啮齿动物体内时，牙周韧带干细胞显示出生成牙骨质/牙周韧带样结构并促进牙周组织修复的能力。
我们的研究结果表明，牙周韧带含有在体内有可能生成牙骨质/牙周韧带样组织的干细胞。这些细胞可从易于获取的组织资源中获得并在体外扩增，移植这些细胞可能有望成为一种治疗方法，用于重建因牙周疾病而破坏的组织。
