title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. caoyu_bj@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: 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. 13683684505@163.com.|Department of Stomatology, Beijing Jishuitan Hospital, No.31, Xinjiekou East Street, Xicheng District, Beijing, 100035, P.R. China. 13683684505@163.com.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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. kazaf-helen@qq.com.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: 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. hujingchao117@hotmail.com.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, P.R. China. 18511712135@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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. wang54384@163.com.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Fan
authors.affiliation: 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. 929814026@qq.com.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 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. wjs99330@163.com.|Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, No.10 You An Men Wai Tou Tiao,, Beijing, 100069, P.R. China. wjs99330@163.com.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, P.R. China. wuct@nic.bmi.ac.cn.
authors.forename: Chu-Tse
authors.initials: CT
authors.lastname: Wu
authors.affiliation: 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. slwang@ccmu.edu.cn.|Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, No.10 You An Men Wai Tou Tiao,, Beijing, 100069, P.R. China. slwang@ccmu.edu.cn.
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001861:Bone Regeneration; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism*; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D010513:Periodontal Ligament / Q000166:cytology; D010518:Periodontitis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D010519:Periodontium / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics* / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection
chemical_list: C066855:HGF protein, human; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor