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

Stem Cell Research & Therapy

Songlin Wang⁴  Chu-Tse Wu¹  Jingsong Wang⁴  Chunmei Zhang³  Zhipeng Fan³  Hua Wang¹  Jingchao Hu³  Yilin Xie³  Zhenhai Liu²  Yu Cao³ 

[1] Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, P.R. China;Department of Stomatology, Beijing Jishuitan Hospital, No.31, Xinjiekou East Street, Xicheng District, Beijing 100035, P.R. China;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 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

关键词: periodontal regeneration;    hepatocyte growth factor;    cell sheet;    cell injection;    dental pulp stem cells;   

Others  :  1235594
DOI  :  10.1186/s13287-015-0244-5

 received in 2015-08-12, accepted in 2015-11-23,  发布年份 2015

【 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.

【 授权许可】

   
2015 Cao et al.

【 图 表 】

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