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.
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.
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在良好的生产规范下，腺病毒介导的肝细胞生长因子基因转移至人牙髓干细胞，提高了猪牙周再生的潜力
DOI：
10.1186/s13287-015-0244-5
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发表时间：
2015-12-15
影响因子：
7.5
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Cao Y;Liu Z;Xie Y;Hu J;Wang H;Fan Z;Zhang C;Wang J;Wu CT;Wang S
牙周炎是人类最常见的传染病之一。我们之前通过移植自体牙周膜干细胞(PDLSCs)和PDLSC片促进了猪模型中显着的牙周组织再生。我们还通过局部注射异基因骨髓间充质干细胞促进了大鼠模型的牙周组织再生。本研究旨在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。在本研究中，我们将携带HGF基因的腺病毒在良好的制造规范(GMP)条件下导入人DPSCs(HGF-hDPSCs)。这些细胞随后被移植到猪的牙周再生模型中。用20头小型猪制作宽5 mm、长7 mm、深3 mm的牙周炎模型。12周后，对再生牙周组织进行临床、放射学、定量和组织学评价，以比较细胞移植治疗后的牙周再生情况。我们的研究表明，在这一大型动物模型中注射HGF-hDPSCs可以显著促进牙周骨再生和软组织愈合。与注射游离细胞相比，hDPSC或HGF-hDPSC片显示出更好的牙周组织再生。然而，这些床单需要手术放置；因此，它们适合手术管理的牙周炎治疗。腺病毒介导的HGF基因转移可显著减少缺氧或无血清培养条件下hDPSC的凋亡率，促进血管再生。本研究表明，在GMP条件下培养的HGF-hDPSCs显著促进了猪牙周骨的再生，为牙周再生提供了潜在的临床应用前景。本文的在线版本(doi：10.1186/s13287-0150244-5)包含补充材料，授权用户可以使用。
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. 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. 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. 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. The online version of this article (doi:10.1186/s13287-015-0244-5) contains supplementary material, which is available to authorized users.