在药品生产质量管理规范（GMP）条件下，腺病毒介导的肝细胞生长因子基因转染人牙髓干细胞可提高其在猪体内牙周再生的潜能。
Adenovirus-mediated transfer of hepatocyte growth factor gene to human dental pulp stem cells under good manufacturing practice improves their potential for periodontal regeneration in swine.
作者信息
Cao Yu, Liu Zhenhai, Xie Yilin, Hu Jingchao, Wang Hua, Fan Zhipeng, Zhang Chunmei, Wang Jingsong, Wu Chu-Tse, Wang Songlin
机构信息
Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No. 4, Beijing, 100050, P.R. China.
Department of Stomatology, Beijing Jishuitan Hospital, No.31, Xinjiekou East Street, Xicheng District, Beijing, 100035, P.R. China.
出版信息
Stem Cell Res Ther. 2015 Dec 15;6:249. doi: 10.1186/s13287-015-0244-5.
INTRODUCTION
Periodontitis is one of the most widespread infectious diseases in humans. We previously promoted significant periodontal tissue regeneration in swine models with the transplantation of autologous periodontal ligament stem cells (PDLSCs) and PDLSC sheet. We also promoted periodontal tissue regeneration in a rat model with a local injection of allogeneic bone marrow mesenchymal stem cells. The purpose of the present study is to investigate the roles of the hepatocyte growth factor (HGF) and human dental pulp stem cells (DPSCs) in periodontal tissue regeneration in swine.
METHOD
In the present study, we transferred an adenovirus that carried HGF gene into human DPSCs (HGF-hDPSCs) under good manufacturing practice (GMP) conditions. These cells were then transplanted into a swine model for periodontal regeneration. Twenty miniature pigs were used to generate periodontitis with bone defect of 5 mm in width, 7 mm in length, and 3 mm in depth. After 12 weeks, clinical, radiological, quantitative and histological assessment of regenerated periodontal tissues was performed to compare periodontal regeneration in swine treated with cell implantation.
RESULTS
Our study showed that injecting HGF-hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. A hDPSC or HGF-hDPSC sheet showed superior periodontal tissue regeneration compared to the injection of dissociated cells. However, the sheets required surgical placement; thus, they were suitable for surgically-managed periodontitis treatments. The adenovirus-mediated transfer of the HGF gene markedly decreased hDPSC apoptosis in a hypoxic environment or in serum-free medium, and it increased blood vessel regeneration.
CONCLUSION
This study indicated that HGF-hDPSCs produced under GMP conditions significantly improved periodontal bone regeneration in swine; thus, this method represents a potential clinical application for periodontal regeneration.
引言
牙周炎是人类中最普遍的传染病之一。我们之前通过自体牙周膜干细胞（PDLSCs）和PDLSC片移植在猪模型中促进了显著的牙周组织再生。我们还通过局部注射同种异体骨髓间充质干细胞在大鼠模型中促进了牙周组织再生。本研究的目的是探讨肝细胞生长因子（HGF）和人牙髓干细胞（DPSCs）在猪牙周组织再生中的作用。
方法
在本研究中，我们在良好生产规范（GMP）条件下将携带HGF基因的腺病毒转导入人DPSCs（HGF-hDPSCs）。然后将这些细胞移植到猪牙周再生模型中。使用20只小型猪制造宽度为5mm、长度为7mm、深度为3mm骨缺损的牙周炎。12周后，对再生牙周组织进行临床、放射学、定量和组织学评估，以比较细胞植入治疗猪的牙周再生情况。
结果
我们的研究表明，将HGF-hDPSCs注射到这种大型动物模型中可显著改善牙周骨再生和软组织愈合。与注射解离细胞相比，hDPSC或HGF-hDPSC片显示出更好的牙周组织再生。然而，这些片需要手术放置；因此，它们适用于手术治疗的牙周炎。腺病毒介导的HGF基因转移在低氧环境或无血清培养基中显著降低hDPSC凋亡，并增加血管再生。
结论
本研究表明，在GMP条件下产生的HGF-hDPSCs显著改善了猪的牙周骨再生；因此，该方法代表了牙周再生的潜在临床应用。
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