Dataset Information

Periodontal regeneration with autologous periodontal ligament-derived cell sheets - A safety and efficacy study in ten patients.

ABSTRACT:

Background

Periodontitis results in the destruction of tooth-supporting periodontal tissues and does not have the ability to heal spontaneously. Various approaches have been introduced to regenerate periodontal tissues; however, these approaches have limited efficacy for treating severe defects. Cytotherapies combine stem cell biology and tissue engineering to form a promising approach for overcoming these limitations. In this study, we isolated periodontal ligament (PDL)-derived cells from patients and created cell sheets with "Cell Sheet Engineering Technology", using temperature responsive culture dishes, in which all the cultured cells can be harvested as an intact transplantable cell sheet by reducing the temperature of the culture dish. Subsequently, the safety and efficacy of autologous PDL-derived cell sheets were evaluated in a clinical setting.

Methods

A single-arm and single-institute clinical study was performed to verify the safety and efficacy of autologous PDL-derived cell sheets in patients with periodontitis. Wisdom teeth were extracted from patients diagnosed with chronic periodontitis, ranging in age from 33 to 63 years (mean [±SD], 46 ± 12), and periodontal tissues were scraped for cell sources. Three-layered PDL-derived cell sheets were constructed using temperature-responsive culture dishes and transplanted in an autologous fashion following standard flap surgeries. Bony defects were filled with beta-tricalcium phosphate granules. Clinical variables were evaluated at baseline, 3 months, and 6 months. Cone-beam computed tomography was performed at baseline and 6 months. Additionally, mid-long-term follow-up has been performed with patients' agreements.

Results

Our method was found to be safe and no severe adverse events were identified. All the findings, including reduction of periodontal probing depth (mean ± SD, 3.2 ± 1.9 mm), clinical attachment gain (2.5 ± 2.6 mm), and increase of radiographic bone height (2.3 ± 1.8 mm), were improved in all 10 cases at 6 months after the transplantation. These therapeutic effects were sustained during a mean follow-up period of 55 ± 19 months, and there were no serious adverse events.

Conclusions

The results of this study validate the safety and efficacy of autologous PDL-derived cell sheets in severe periodontal defects, and the stability of this efficacy during mid-long-term follow up. This cytotherapeutic approach, based on cell sheet engineering, offers an innovative strategy to treat the recognized unmet need of treating severe periodontal defects.

SUBMITTER: Iwata T

PROVIDER: S-EPMC6222282 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Periodontal regeneration with autologous periodontal ligament-derived cell sheets - A safety and efficacy study in ten patients.

Iwata Takanori T Yamato Masayuki M Washio Kaoru K Yoshida Toshiyuki T Tsumanuma Yuka Y Yamada Azusa A Onizuka Satoru S Izumi Yuichi Y Ando Tomohiro T Okano Teruo T Ishikawa Isao I

Regenerative therapy 20180824

<h4>Background</h4>Periodontitis results in the destruction of tooth-supporting periodontal tissues and does not have the ability to heal spontaneously. Various approaches have been introduced to regenerate periodontal tissues; however, these approaches have limited efficacy for treating severe defects. Cytotherapies combine stem cell biology and tissue engineering to form a promising approach for overcoming these limitations. In this study, we isolated periodontal ligament (PDL)-derived cells f ...[more]

PMID: 30525074

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Project description:ObjectivePer-implantitis is one of the implant treatment complications. Dentists have failed to restore damaged periodontium by using conventional therapies. Tissue engineering (stem cells, scaffold and growth factors) aims to reconstruct natural tissues. The paper aimed to isolate both periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMMSCs) and use them in a co-culture method to create three-layered cell sheets for reconstructing natural periodontal ligament (PDL) tissue.Materials and methodsBMMSCs were isolated from rabbit tibia and femur, and PDLSC culture was established from the lower right incisor. The cells were co-cultured to induce BMMSC differentiation into PDL cells. Cell morphology, stem cells and PDL-specific markers (CD90, CD34, and periostin) were also detected using immunofluorescent assay. Co-cultured cell monolayers were detached using temperature-responsive tissue culture dishes and collagen graft to create the three-layer construct. The 3D-engineered tissue was examined histologically and by field emission scanning electron microscopy (FESEM).ResultsBMMSCs co-cultured with PDLSCs successfully induced more PDL cells. The newly induced PDL cells exhibited periostin and CD90 expression. Fluorescence green intensity was measured for the co-cultured cells that were stained with periostin, the mean fluorescence green intensity (periostin expression) was significantly higher for the newly induced PDL cells after 1, 2, and 3 weeks when compared with control (BM-MSCs), at 21 days non-significant difference was measured when compared with control (PDLSCs).The results showed the successful formation of 3D multilayer PDL tissue. Histological cross-section showed cell sheets and the stable adhesion between them. FESEM examination was conducted for the cross-section, showing three-layered cell sheets with stable adhesion between cells.ConclusionsThe results of this paper report that the three layered-cell sheets were successfully constructed by the novel use of collagen graft as a scaffold to be used in treatment of periodontitis and to envelop the dental implants to create biohybrid implant.

Project description:BackgroundEvidence has demonstrated conditioned medium (CM) from periodontal ligament stem cells (PDLSCs) improved periodontal regeneration. Gingival mesenchymal stem cells (GMSCs) have been considered an alternative strategy for regenerative medicine. To determine whether GMSC-CM could promote periodontal wound healing, we compared the effects of GMSC-CM and PDLSC-CM on periodontal regeneration and the underlying mechanisms in rat periodontal defects.MethodsCell-free CMs were collected from PDLSCs, GMSCs, and gingival fibroblasts (GFs) using ultracentrifugation (100-fold concentration). Periodontal defects were created on the buccal side of the first molar in the left mandible of 90 rats by a surgical method. Collagen membranes loaded with concentrated CMs (α-MEM, GF-CM, GMSC-CM, PDLSC-CM) were transplanted into periodontal defects. After 1, 2, and 4 weeks, the animals were sacrificed and specimens including the first molar and the surrounding tissues were separated and decalcified. Hematoxylin-eosin and Masson's trichrome staining were performed to evaluate periodontal regeneration. Immunohistochemical staining for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 was conducted to analyze inflammation. Immunohistochemistry of BSP-II and Runx2 was performed to analyze osteoblast differentiation.ResultsHistological analysis showed the amount of newly formed periodontal tissue was significantly higher in both the GMSC-CM and PDLSC-CM groups than in the other groups, with no significant difference between these two groups. At 1 and 2 weeks, the expression levels of TNF-α and IL-1β were significantly lower in the GMSC-CM and PDLSC-CM groups than in the other three groups, while there was no significant difference between these two groups. IL-10 expression was significantly higher in the GMSC-CM group than in the PDLSC-CM group and the other three groups. At 1, 2, and 4 weeks, BSP-II and Runx2 expressions were significantly higher in the GMSC-CM and PDLSC-CM groups than in the other three groups, with no significant difference between the two groups.ConclusionsOur results demonstrate that GMSC-CM transplantation can significantly promote periodontal regeneration in rats and achieve the same effect as PDLSC-CM. The mechanism of periodontal regeneration may involve the regulation of inflammatory factors and the promotion of osteogenic differentiation of bone progenitor cells in the wound region by CMs from MSCs.

Project description:BackgroundPeriodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry.MethodsWe conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss(®)) or the Control group (treatment with GTR and Bio-oss(®) without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure.ResultsA total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However, no statistically significant differences were detected between the Cell group and the Control group (p > 0.05).ConclusionsThis study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell-based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size.Trial registrationNCT01357785 Date registered: 18 May 2011.

Dataset Information

Periodontal regeneration with autologous periodontal ligament-derived cell sheets - A safety and efficacy study in ten patients.

Background

Methods

Results

Conclusions

Publications

Periodontal regeneration with autologous periodontal ligament-derived cell sheets - A safety and efficacy study in ten patients.

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