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

IntroductionPeriodontitis 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.MethodIn 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.ResultsOur 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.ConclusionThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0244-5) contains supplementary material, which is available to authorized users.

Decellularized Swine Dental Pulp as a Bioscaffold for Pulp Regeneration

“…DPSCs were isolated and cultured under good manufacturing practice (GMP) conditions as described in our previous studies [ 20 ]. Patients' teeth were acquired from Beijing Stomatological Hospital, Capital Medical University, and all treatments were performed per the approved guidelines.…”

Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative Stress

“…Research has also confirmed that Nrf2 itself influences the intrinsic and extrinsic apoptosis pathways at different levels [19]. Therefore, we believe that Nrf2 is extremely important in the process of cell apoptosis caused by oxidative stress.…”

The use of human dental pulp stem cells for in vivo bone tissue engineering: A systematic review

“…To study the local bone formation using hDPSCs and SHED, cranial defects were created in rats on 11 manuscri-pts, 25 , 35 , 40 , 41 , 44 , 48 , 49 , 51 , 55 , 56 in mice on 4 manuscripts, 17 , 42 , 59 , 72 and in only one manuscript they were made on rabbits. 61 Furthermore, 10 studies created maxillary and mandibular bone defects 29 , 45 , 46 , 52 , 53 , 58 , 60 , 62 , 65 , 69 to assess the potential of hDPSCs for bone tissue engineering. In 3 out of these 10 studies, the researchers used the alveolar bone to test the tissue engineering strategies after extraction of third molars of maxillary 60 and mandibular 29 , 46 regions in humans.…”

“… 69 Six studies were conducted in different animal models. Among these studies, one used rats and created the bone defect in the anterior part of the maxilla, 58 one used rat and created the defect in the left side of mandible, 62 one used rabbits and created the defect between the first premolar and the mental foramen, 45 one used mini pigs to create the defects in the mesial region of the maxilla and mandibular first molars, 52 one used mini pigs and created the defect in front of the mandibular angle, 53 and one used dogs and created the defect on each side of the inferior mandibular border. 65 Furthermore, one study evaluated the potential of hDPSCs for bone tissue engineering in rabbits tibia submitted to distraction osteogenesis 68 and one study investigated the osteogenic potential of hDPSCs in an ovine model of induced osteonecrosis of femoral head.…”

“…It is important to note that while most studies evaluated the potential of hDPSCs to produce ectopic bone when implanted subcutaneously or intraperitoneally, 18 – 24 , 26 – 28 , 30 , 32 – 34 , 36 – 39 , 43 , 47 , 50 , 54 , 57 , 63 , 66 , 70 , 71 the majority of the recent in vivo studies published applied hDPSCs to repair local bone defects. 17 , 25 , 29 , 31 , 35 , 40 – 42 , 44 – 46 , 48 , 49 , 51 – 53 , 55 , 56 , 58 – 62 , 63 , 65 , 68 , 69 , 72 In...…”