Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing, People's Republic of China.
Stem Cells. 2010 Oct;28(10):1829-38. doi: 10.1002/stem.512.
Periodontitis is one of the most widespread infectious diseases in humans. It is the main cause of tooth loss and associated with a number of systemic diseases. Until now, there is no appropriate method for functional periodontal tissue regeneration. Here, we establish a novel approach of using allogeneic periodontal ligament stem cells (PDLSCs) sheet to curing periodontitis in a miniature pig periodontitis model. Significant periodontal tissue regeneration was achieved in both the autologous and the allogeneic PDLSCs transplantation group at 12 weeks post-PDLSCs transplantation. Based on clinical assessments, computed tomography (CT) scanning, and histological examination, there was no marked difference between the autologous and allogeneic PDLSCs transplantation groups. In addition, lack of immunological rejections in the animals that received the allogeneic PDLSCs transplantation was observed. Interestingly, we found that human PDLSCs fail to express human leukocyte antigen (HLA)-II DR and costimulatory molecules. PDLSCs were not able to elicit T-cell proliferation and inhibit T-cell proliferation when stimulated with mismatched major histocompatibility complex molecules. Furthermore, we found that prostaglandin E2 (PGE2) plays a crucial role in PDLSCs-mediated immunomodulation and periodontal tissue regeneration in vitro and in vivo. Our study demonstrated that PDLSCs possess low immunogenicity and marked immunosuppression via PGE2-induced T-cell anergy. We developed a standard technological procedure of using allogeneic PDLSCs to cure periodontitis in swine.
牙周炎是人类最广泛的传染病之一。它是牙齿脱落的主要原因，并与许多全身性疾病有关。到目前为止，还没有适当的方法来实现功能性牙周组织再生。在这里，我们建立了一种使用同种异体牙周韧带干细胞（PDLSCs）片治疗小型猪牙周炎模型中牙周炎的新方法。在 PDLSCs 移植后 12 周，自体和同种异体 PDLSCs 移植组均实现了显著的牙周组织再生。基于临床评估、计算机断层扫描（CT）扫描和组织学检查，自体和同种异体 PDLSCs 移植组之间没有明显差异。此外，在接受同种异体 PDLSCs 移植的动物中观察到缺乏免疫排斥反应。有趣的是，我们发现人 PDLSCs 未能表达人白细胞抗原（HLA）-II DR 和共刺激分子。当用错配的主要组织相容性复合物分子刺激时，PDLSCs 不能引发 T 细胞增殖并抑制 T 细胞增殖。此外，我们发现前列腺素 E2（PGE2）在 PDLSCs 介导的免疫调节和体内外牙周组织再生中起着关键作用。我们的研究表明，PDLSCs 通过 PGE2 诱导的 T 细胞无能具有低免疫原性和显著的免疫抑制作用。我们开发了一种使用同种异体 PDLSCs 治疗猪牙周炎的标准技术程序。
