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

被引：83

作者：

Cao, Yu ^{[1
]}

Liu, Zhenhai ^{[1
,2
]}

Xie, Yilin ^{[1
]}

Hu, Jingchao ^{[1
]}

Wang, Hua ^{[3
]}

Fan, Zhipeng ^{[1
]}

Zhang, Chunmei ^{[1
]}

Wang, Jingsong ^{[1
,4
]}

Wu, Chu-Tse ^{[3
]}

Wang, Songlin ^{[1
,4
]}

机构：

[1] Capital Med Univ, Sch Stomatol, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Mol Lab Gene Therapy & Tooth Regenerat, Beijing 100050, Peoples R China

[2] Beijing Jishuitan Hosp, Dept Stomatol, Beijing 100035, Peoples R China

[3] Beijing Inst Radiat Med, Dept Expt Hematol, Beijing 100850, Peoples R China

[4] Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China

来源：

STEM CELL RESEARCH & THERAPY | 2015年 / 6卷

基金：

中国国家自然科学基金;

关键词：

dental pulp stem cells; cell injection; cell sheet; hepatocyte growth factor; periodontal regeneration; THERAPY; INJURY; MODEL; HGF;

D O I：

10.1186/s13287-015-0244-5

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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.

引用

页数：13

共 32 条

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