Publications by authors named "Izumi Asahina"

103 Publications

Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study.

J Clin Med 2021 Apr 14;10(8). Epub 2021 Apr 14.

Department of Regenerative Oral Surgery, Institute of Biomedical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at -20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size.
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http://dx.doi.org/10.3390/jcm10081678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070716PMC
April 2021

Gene-activated matrix harboring a miR20a-expressing plasmid promotes rat cranial bone augmentation.

Regen Biomater 2021 Mar 13;8(2):rbaa060. Epub 2021 Mar 13.

Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.

Gene-activated matrix (GAM) has a potential usefulness in bone engineering as an alternate strategy for the lasting release of osteogenic proteins but efficient methods to generate non-viral GAM remain to be established. In this study, we investigated whether an atelocollagen-based GAM containing naked-plasmid () DNAs encoding microRNA (miR) 20a, which may promote osteogenesis via multiple pathways associated with the osteogenic differentiation of mesenchymal stem/progenitor cells (MSCs), facilitates rat cranial bone augmentation. First, we confirmed the osteoblastic differentiation functions of generated DNA encoding miR20a (miR20a) , and its transfection regulated the expression of several of target genes, such as Bambi1 and PPARγ, in rat bone marrow MSCs and induced the increased expression of BMP4. Then, when GAMs fabricated by mixing 100 μl of 2% bovine atelocollagen, 20 mg β-TCP granules and 0.5 mg (3.3 μg/μl) AcGFP plasmid-vectors encoding miR20a were transplanted to rat cranial bone surface, the promoted vertical bone augmentation was clearly recognized up to 8 weeks after transplantation, as were upregulation of VEGFs and BMP4 expressions at the early stages of transplantation. Thus, GAM-based miR delivery may provide an alternative non-viral approach by improving transgene efficacy via a small sequence that can regulate the multiple pathways.
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http://dx.doi.org/10.1093/rb/rbaa060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955717PMC
March 2021

Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irradiation.

J Neural Transm (Vienna) 2020 11 6;127(11):1467-1479. Epub 2020 Oct 6.

Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.

Salivary gland (SG) hypofunction is a common post-radiotherapy complication. Besides the parenchymal damage after irradiation (IR), there are also effects on mesenchymal stem cells (MSCs) which were shown to contribute to regeneration and repair of damaged tissues by differentiating into stromal cell types or releasing vesicles and soluble factors supporting the healing processes. However, there are no adequate reports about their roles during SG damage and regeneration so far. Using an irradiated SG mouse model, we performed certain immunostainings on tissue sections of submandibular glands at different time points after IR. Immunostaining for CD31 revealed that already one day after IR, vascular impairment was induced at the level of capillaries. In addition, the expression of CD44-a marker of acinar cells-diminished gradually after IR and, by 20 weeks, almost disappeared. In contrast, the number of CD34-positive cells significantly increased 4 weeks after IR and some of the CD34-positive cells were found to reside within the adventitia of arteries and veins. Laser confocal microscopic analyses revealed an accumulation of CD34-positive cells within the area of damaged capillaries where they were in close contact to the CD31-positive endothelial cells. At 4 weeks after IR, a fraction of the CD34-positive cells underwent differentiation into α-SMA-positive cells, which suggests that they may contribute to regeneration of smooth muscle cells and/or pericytes covering the small vessels from the outside. In conclusion, SG-resident CD34-positive cells represent a population of progenitors that could contribute to new vessel formation and/or remodeling of the pre-existing vessels after IR and thus, might be an important player during SG tissue healing.
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http://dx.doi.org/10.1007/s00702-020-02256-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578140PMC
November 2020

Assessment of safety and efficacy of antimicrobial photodynamic therapy for peri-implant disease.

Photodiagnosis Photodyn Ther 2020 Sep 11;31:101936. Epub 2020 Aug 11.

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan; Center for Oral and Maxillofacial Implants, Nagasaki University Hospital, Japan.

Background: There is no reliable treatment procedure for peri-implant disease, despite the rise in its incidence. This study sought to evaluate the short-term safety and efficacy of antimicrobial photodynamic therapy (a-PDT) on peri-implantitis by assessing the volume of pus discharge after a-PDT.

Methods: Patients with pus discharge from a peri-implant pocket were recruited from December 1st, 2019 to April 30th, 2020. The enrolled implants were randomly assigned to one of two groups, the irrigation and a-PDT groups. Their peri-implant pocket was irrigated with normal saline in the irrigation group, and a saline irrigation and subsequent a-PDT with toluidine blue (TB) was performed in the a-PDT group. The safety and efficacy of a-PDT were assessed 7 days after treatment.

Results: Twenty-five implants in 21 patients (irrigation group; 13 implants, a-PDT group; 12 implants) were registered. No complication was observed after a-PDT. Pus discharge was decreased in 7 of 12 implants (58.3 %) in the a-PDT group, and in 2 of 13 implants (15.4 %) in the irrigation group. According to Fisher's exact test, a-PDT resulted in a statistically significant decrease in pus discharge compared to irrigation alone (p = 0.0414).

Conclusions: a-PDT was confirmed to be a safe treatment for peri-implantitis, and the short-term efficacy of a-PDT with TB on peri-implantitis was clarified. Nevertheless, its efficacy remains restricted, and a new combination therapy of a-PDT and decontamination procedures is expected to be developed in future.
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http://dx.doi.org/10.1016/j.pdpdt.2020.101936DOI Listing
September 2020

Evaluation of Poly Lactic-co-Glycolic Acid-Coated β-Tricalcium Phosphate Bone Substitute as a Graft Material for Ridge Preservation after Tooth Extraction in Dog Mandible: A Comparative Study with Conventional β-Tricalcium Phosphate Granules.

Materials (Basel) 2020 Aug 5;13(16). Epub 2020 Aug 5.

Department of Regenerative Oral Surgery, Institute of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan.

This study aims to evaluate the safety and efficacy of a poly lactic-co-glycolic acid (PLGA)-coated β-tricalcium phosphate (β-TCP) with N-methyl-2-pyrrolidone (NMP) liquid activator (PLGA/β-TCP) on alveolar ridge preservation after tooth extraction in dog mandible. Thirty-two extraction sites were prepared in eight dog mandibles. A distal root of the mandibular premolar was extracted and randomly grafted with one of the following bone substitutes: (1) PLGA/β-TCP, (2) β-TCP, or (3) left empty as a control, and wounds were closed with keratinized mucosa graft. Post-operative wound healing was observed and scored to evaluate safety. After 12 and 24 weeks, the bone regeneration was evaluated with micro-computed tomography (CT) images and histomorphometric analyses. Gingival epithelization progressed over time without complication or infection. Micro-CT images and histological observation revealed that both PLGA/β-TCP and β-TCP granules supported sufficient new bone formation. Although bone formation and substrate resorption were delayed slightly with the PLGA and the NMP-containing plasticizer as compared to those treated with conventional β-TCP, it can be concluded that the PLGA and the NMP-containing plasticizer that facilitated the in situ hardening properties of the material had no negative influence on the biocompatibility of the material.
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http://dx.doi.org/10.3390/ma13163452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475865PMC
August 2020

Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism.

J Pediatr Endocrinol Metab 2020 Jul;33(7):963-966

Department of Pediatrics, Nagasaki University Hospital, Nagasaki, Japan.

Background Denosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand, which strongly suppresses osteoclasts. Cherubism is a rare autosomal dominant disorder characterized by symmetrical swelling of the jaws, in which the bone is replaced by a fibrous granuloma containing osteoclast-like giant cells. Case presentation We report the efficacy and safety of denosumab treatment in a prepubertal boy with progressive cherubism. The treatment consisting of eight subcutaneous denosumab injections (120 mg/dose) in 6 months not only suppressed the expansion of the osteolytic lesions but also dramatically ossified them. However, a transiently decreased growth rate and rebounded asymptomatic hypercalcemia were associated with the treatment. Conclusions The present case demonstrated the therapeutic potential of denosumab for treatment of cherubism, although adverse effects, especially those on childhood growth, remain obscure. Further studies are needed to establish a safe and effective protocol for denosumab treatment of children.
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http://dx.doi.org/10.1515/jpem-2019-0581DOI Listing
July 2020

Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia).

Medicine (Baltimore) 2020 Jun;99(26):e20788

Department of Regenerative Oral Surgery, Unit of Translational Medicine.

Background: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia.

Methods/design: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy.

Discussion: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia.

Trial Registration: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057.
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http://dx.doi.org/10.1097/MD.0000000000020788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328916PMC
June 2020

Movement of the proximal segment after intraoral vertical ramus osteotomy versus short lingual osteotomy with physiological positioning strategy.

J Craniomaxillofac Surg 2020 Jul 25;48(7):638-644. Epub 2020 Apr 25.

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588 Japan.

Purpose: To clarify whether intraoral vertical ramus osteotomy (IVRO) or short lingual osteotomy (SLO) induces less proximal segmental movement after surgery without bone fixation.

Methods: This study included patients who underwent IVRO or SLO without bone fixation. Cephalograms were taken before surgery (T1), immediately after surgery (T2), and >6 months after surgery (T3) to assess postoperative movement of the proximal segment and skeletal stability. The condylar angle was measured using computed tomography images taken at T1 and T3 to assess rotation.

Results: Ninety patients were included (IVRO, n = 25; SLO, n = 65). The proximal segment swung laterally on the frontal cephalogram in the asymmetrical IVRO group at T3. The condylar head was rotated outwardly 6.52 ± 4.49° (p < 0.0001) in the symmetrical IVRO group and 8.06 ± 6.88° (p = 0.030) on the non-deviated side in the asymmetrical IVRO group at T3. The condyles were almost stable in the SLO group. Temporomandibular joint disorders were found in 2 of 22 IVRO patients and in 2 of 42 SLO patients with asymmetry at T3.

Conclusion: This study suggests that SLO with the physiological positioning strategy (PPS) should be preferred over IVRO with the PPS whenever possible.
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http://dx.doi.org/10.1016/j.jcms.2020.04.006DOI Listing
July 2020

Do not keep it simple: recent advances in the generation of complex organoids.

J Neural Transm (Vienna) 2020 11 8;127(11):1569-1577. Epub 2020 May 8.

Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.

3D cell culture models which closely resemble real human tissues are of high interest for disease modelling, drug screening as well as a deeper understanding of human developmental biology. Such structures are termed organoids. Within the last years, several human organoid models were described. These are usually stem cell derived, arise by self-organization, mimic mechanisms of normal tissue development, show typical organ morphogenesis and recapitulate at least some organ specific functions. Many tissues have been reproduced in vitro such as gut, liver, lung, kidney and brain. The resulting entities can be either derived from an adult stem cell population, or generated from pluripotent stem cells using a specific differentiation protocol. However, many organoid models only recapitulate the organs parenchyma but are devoid of stromal components such as blood vessels, connective tissue and inflammatory cells. Recent studies show that the incorporation of endothelial and mesenchymal cells into organoids improved their maturation and might be required to create fully functional micro-tissues, which will allow deeper insights into human embryogenesis as well as disease development and progression. In this review article, we will summarize and discuss recent works trying to incorporate stromal components into organoids, with a special focus on neural organoid models.
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http://dx.doi.org/10.1007/s00702-020-02198-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577912PMC
November 2020

Clinical study of octacalcium phosphate and collagen composite in oral and maxillofacial surgery.

J Tissue Eng 2020 Jan-Dec;11:2041731419896449. Epub 2020 Jan 23.

Department of Oral Medicine and Surgery, Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan.

Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.
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http://dx.doi.org/10.1177/2041731419896449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978823PMC
January 2020

A stable protocol for the fabrication of transplantable human oral mucosal epithelial cell sheets for clinical application.

Regen Ther 2020 Jun 16;14:87-94. Epub 2020 Jan 16.

Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8-1 Kawada-Cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Introduction: Cultured stratified epithelial cell sheets have been clinically utilized as transplantable grafts for the regeneration of epithelial tissues, such as the esophagus, cornea, skin, and intraoral cavity. These cell sheets are expected to gain widespread use as regenerative medicine products and save many patients. For this purpose, establishing and disseminating the stale protocol of fabricating the cell sheet is crucial. The fabrication of cultured stratified epithelial cell sheets consists of many important steps, and since the patients' epithelial cell conditions vary widely and are sometimes unstable, the qualities of the epithelial cell grafts are likewise potentially unstable. Therefore, in this paper, we report the stable protocol for fabrication of the transplantable cell sheet particularly from patient-derived oral mucosal tissues.

Methods: Serum extracted from blood and buccal mucosal tissue were collected in Nagasaki University and transported to Tokyo Women's Medical University. Oral mucosal epithelial cells were collected by minimum trypsin method, and this treatment was studied whether to be a critical procedure. After 14 days cultivation, cultured cells were examined whether to be transplantable as cell sheets.

Results: We successfully transported buccal mucosal tissue and serum without damage and contamination. Oral mucosal epithelial cells were collected with high viability by minimum trypsin method. Finally, we succeeded to stably fabricate oral mucosal epithelial cell sheets in all 10 patients.

Conclusions: We established a stable protocol for the fabrication of human oral mucosal epithelial cell sheets and their transportation in clinical settings in this study. These methodologies could also be basis for transplantation therapy using cultured cell sheets of various types other than oral mucosal epithelial cell and will contribute largely to the future development of regenerative medicine.
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http://dx.doi.org/10.1016/j.reth.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970131PMC
June 2020

Full Regeneration of Maxillary Alveolar Bone Using Autogenous Partially Demineralized Dentin Matrix and Particulate Cancellous Bone and Marrow for Implant-Supported Full Arch Rehabilitation.

J Oral Implantol 2020 Apr;46(2):122-127

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Autogenous partially demineralized dentin matrix (APDDM) has been reportedly used as a superior bone graft material. A 52-year-old Japanese man who exhibited severe periodontitis was referred for oral rehabilitation. He underwent wide-range anterior maxillary alveolar bone and bilateral sinus floor augmentation by grafting of a mixture of APDDM and particulate cancellous bone and marrow (PCBM); subsequently, he underwent implant-supported full arch rehabilitation. He has been followed up for 4 years after placement of the final restoration without any complications, and his physiological bone volume has been maintained. APDDM constitutes an alternative treatment that may increase the volume of graft material and might prevent rapid resorption of PCBM, because APDDM served as a scaffold for osteoblasts from PCBM. When possible, it may be useful to apply APDDM as a graft material with PCBM for large-volume alveolar bone regeneration.
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http://dx.doi.org/10.1563/aaid-joi-D-19-00315DOI Listing
April 2020

Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis.

Stem Cells Int 2019 12;2019:4214281. Epub 2019 Nov 12.

Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis.
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http://dx.doi.org/10.1155/2019/4214281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875206PMC
November 2019

Anti-inflammatory and vasculogenic conditioning of peripheral blood mononuclear cells reinforces their therapeutic potential for radiation-injured salivary glands.

Stem Cell Res Ther 2019 10 17;10(1):304. Epub 2019 Oct 17.

Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: There are currently no effective treatments available for patients with irreversible loss of salivary gland (SG) function caused by radiation therapy for head and neck cancer. In this study, we have developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs) and investigated whether such effectively conditioned PBMNCs (E-MNCs) could regenerate radiation-injured SGs and ameliorate salivary secretory function in mice.

Methods: Mouse PBMNCs were expanded in primary serum-free culture with five vasculogenic proteins for 5 days, and then the resulting cells (E-MNCs) were analyzed for their characteristics. Subsequently, 5 × 10 E-MNCs (labeled with EGFP in some experiments) were injected intra-glandularly into a mouse model of radiation-injured atrophic submandibular glands. After 2-3 weeks, the submandibular glands were harvested, and then the injected E-MNCs were tracked. Four, 8, and 12 weeks after irradiation (IR), salivary outputs were measured to evaluate the recovery of secretory function, and the gland tissues were harvested for histological and gene expression analyses to clarify the effects of cell transplantation.

Results: The resulting E-MNCs contained an enriched population of definitive CD11b/CD206-positive (M2 macrophage-like) cells and showed anti-inflammatory and vasculogenic characteristics. Salivary secretory function in E-MNC-transplanted mice gradually recovered after 4 weeks post-irradiation (post-IR) and reached 3.8-fold higher than that of non-transplanted mice at 12 weeks. EGFP-expressing E-MNCs were detected in a portion of the vascular endothelium and perivascular gland tissues at 2 weeks post-IR, but mainly in some microvessels at 3 weeks. Between 4 and 12 weeks post-IR, mRNA expression and histological analyses revealed that E-MNC transplantation reduced the expression of inflammatory genes and increased the level of tissue-regenerative activities such as stem cell markers, cell proliferation, and blood vessel formation. At 12 weeks post-IR, the areas of acinar and ductal cells regenerated, and the glands had less fibrosis.

Conclusions: This effective conditioning of PBMNCs is a simple, rapid, and efficient method that provides a non-invasive source of therapeutic cells for regenerating radiation-injured atrophic SGs.
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http://dx.doi.org/10.1186/s13287-019-1414-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798785PMC
October 2019

Systemic administration of quality- and quantity-controlled PBMNCs reduces bisphosphonate-related osteonecrosis of jaw-like lesions in mice.

Stem Cell Res Ther 2019 07 16;10(1):209. Epub 2019 Jul 16.

Department of Applied Prosthodontics, Institute of Biomedical Sciences, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8588, Japan.

Background: Definitive treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) have not been developed. Cell-based therapy is an attractive treatment method for intractable diseases in the medical and dental fields; however, approval has been challenging in dentistry. Recently, we developed quality- and quantity (QQ)-controlled peripheral blood mononuclear cells (PBMNCs) that have anti-inflammatory and pro-angiogenesis effects. The aim of this study was to investigate the effects of QQ-controlled PBMNC transplantation on BRONJ-like lesions in mice.

Methods: To create high-prevalence BRONJ-like lesions, cyclophosphamide (CY) and zoledronate (ZA) were used with tooth extraction. Drug treatment was performed for 5 weeks. QQ-controlled PBMNC transplantation was performed immediately following tooth extraction of both maxillary first molars at 3 weeks after drug administration. Mice were euthanized at 2 weeks post-extraction. Histomorphometric and immunohistochemical analyses, microcomputed tomography assessment, and quantitative polymerase chain reaction evaluation were conducted using maxillae and long bones.

Results: ZA effects on long bones were noted, regardless of CY. Severely inhibited osseous and soft tissue wound healing of tooth extraction sockets was induced by CY/ZA combination therapy, which was diagnosed as BRONJ-like lesions. QQ-controlled PBMNC transplantation reduced BRONJ-like lesions by improving soft tissue healing with increased M1 and M2 macrophages and enhanced neovascularization in the connective tissue of tooth extraction sockets. QQ-controlled PBMNC transplantation also reduced inflammation by decreasing polymorphonuclear cells and TNF-α expression in the tooth extraction sockets. Additionally, QQ-controlled PBMNC transplantation partially improved osseous healing of tooth extraction sockets. Interestingly, only 20,000 QQ-controlled PBMNCs per mouse induced these transplantation effects. QQ-controlled PBMNC transplantation did not affect the systemic microenvironment.

Conclusions: Our findings suggest that transplantation of a small amount of QQ-controlled PBMNCs may become novel therapeutic or prevention strategies for BRONJ without any adverse side effects.
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http://dx.doi.org/10.1186/s13287-019-1308-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636115PMC
July 2019

First clinical application of octacalcium phosphate collagen composite on bone regeneration in maxillary sinus floor augmentation: A prospective, single-arm, open-label clinical trial.

J Biomed Mater Res B Appl Biomater 2020 01 13;108(1):243-252. Epub 2019 Apr 13.

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

The overall objective of this study was to assess the safety and efficacy of OCP/Col as a bone substitute material for bone regeneration during sinus floor augmentation. Maxillary sinus floor augmentation was performed thorough lateral window approach. According to the height of host bone, simultaneous approach (≥5 mm) or staged approach (less than 5 mm) was applied. In this research, clinical findings of dental implant treatment after setting the restorations were set as a primary endpoint in both approaches (infection, inflammation around the implant, movement of the implant, pain, sensory disorder, and bone resorption around the implant body on radiological evaluation.). In staged approach, histological evaluation of bone biopsy specimen was also conducted. As secondary endpoints, hounsfield unit (HU) value, vertical bone height, implant stability quotient (ISQ), and adverse events during the research were evaluated. In all cases, as a primary endpoint, clinical findings after setting the restorations were uneventful with no adverse events. Histological structure demonstrated mature bone derived from OCP/Col. In the ossified area, osteogenesis was observed around OCP granules, and osteoblast-like cells were arrayed around OCP granules. Osteocyte encapsulation was recognized in the new bone. HU increased over time with both approaches. Vertical bone height significantly increased at 3 months postoperatively, and maintained during follow-up. ISQ increased with both approaches. In particular, ISQ was significantly increased with the staged approach. This clinical trial demonstrated the safety and efficacy of OCP/Col for bone regeneration in maxillary sinus floor augmentation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:243-252, 2020.
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http://dx.doi.org/10.1002/jbm.b.34384DOI Listing
January 2020

KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1.

Sci Rep 2019 03 5;9(1):3523. Epub 2019 Mar 5.

Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan.

Kelch repeat and BTB domain-containing protein 11 (KBTBD11) is a member of the KBTBD subfamily of proteins that possess a BTB domain and Kelch repeats. Despite the presence of the Kbtbd11 gene in mammalian genomes, there are few reports about KBTBD11 at present. In this study, we identified the novel protein KBTBD11 as a negative regulator of osteoclast differentiation. We found that expression of KBTBD11 increased during osteoclastogenesis. Small-interfering-RNA-mediated knockdown of KBTBD11 enhanced osteoclast formation, and markedly increased the expression of several osteoclast marker genes compared with control cells. Conversely, KBTBD11 overexpression impaired osteoclast differentiation, and decreased the expression of osteoclast marker genes. Among six major signaling pathways regulating osteoclast differentiation, KBTBD11 predominantly influenced the nuclear factor of activated T cell cytoplasmic-1 (NFATc1) pathway. Mechanistically, KBTBD11 was found to interact with an E3 ubiquitin ligase, Cullin3. Further experiments involving immunoprecipitation and treatment with MG132, a proteasome inhibitor, showed that the KBTBD11-Cullin3 promotes ubiquitination and degradation of NFATc1 by the proteasome. Considering that NFATc1 is an essential factor for osteoclast differentiation, the KBTBD11 and Cullin3 probably regulate the levels of NFATc1 through the ubiquitin-proteasome degradation system. Thus, KBTBD11 negatively modulates osteoclast differentiation by controlling Cullin3-mediated ubiquitination of NFATc1.
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http://dx.doi.org/10.1038/s41598-019-40240-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401029PMC
March 2019

Alveolar bone preservation by a hydroxyapatite/collagen composite material after tooth extraction.

Clin Oral Investig 2019 May 9;23(5):2413-2419. Epub 2018 Oct 9.

Department of Regenerative Oral Surgery, Institute of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.

Objective: The aim of this study was to assess the effectiveness of a hydroxyapatite/collagen composite material (HAp/Col) for preservation of alveolar bone after tooth extraction.

Materials And Methods: HAp/Col was applied to the alveolus bone ridge preservation after tooth extraction, because of subsequent dental implant placement in 35 regions of 24 patients (mean age, 59.3 years; range, 25-81 years). Cone beam computed tomography was used to assess changes in alveolar bone at the extraction site before and at 3 months (mean, 13.7 weeks; range, 10-17 weeks) after tooth extraction. Changes in height and width of the alveolar bone were measured to evaluate bone reduction after surgery. Bone biopsy was performed at 11 regions of dental implant placement to observe bone regeneration and remaining material in the extraction socket.

Results: The alveolar bone height was decreased by 0.00 ± 2.44 mm at the buccal side and 0.35 ± 1.73 mm at the lingual side, while the width was decreased by 1.02 ± 1.64 mm at 3 months after surgery. The middle of the socket floor was elevated by 5.71 ± 3.45 mm at 3 months after surgery. Bone biopsy specimens revealed no remaining implanted material, and approximately 49.79 ± 14.41% of the specimens were occupied by bone tissue.

Conclusions: According to the result of this study, HAp/Col is a reliable material to presearve alveolar bone after tooth extraction.

Clinical Relevance: HAp/Col contributes dental implant treatment due to maintain the alveolar bone after tooth extraction.
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http://dx.doi.org/10.1007/s00784-018-2705-6DOI Listing
May 2019

Clinical study of guided bone regeneration with resorbable polylactide-co-glycolide acid membrane.

Odontology 2018 Jul 10;106(3):334-339. Epub 2018 Feb 10.

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.

The guided bone regeneration (GBR) technique is often applied to provide sufficient bone for ideal implant placement. The objective of this study was to evaluate whether GC membrane, which has already been used for guided tissue regeneration (GTR), can also be available for GBR. Twenty-three implants in 18 patients were evaluated in the study. All patients underwent implant placement with GBR using GC membrane. Cone-beam computed tomography was performed at 13-30 weeks after surgery and the amount of augmented bone was assessed. The implant stability quotient (ISQ) was measured at the second operation to evaluate implant stability. Although wound dehiscence was observed at 4 of 23 regions (17.4%), all wounds closed quickly without any events by additional antibiotic administration. GBR-induced bone augmentation of 0.70-2.56 mm horizontally and 0-6.82 mm vertically. Only 0.18 mm of bone recession was observed at 16-24 months after implant placement. GBR with GC membrane induced sufficient bone augmentation, leading to successful implant treatment. The present results suggest that GC membrane is available not only for GTR, but also for GBR.
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http://dx.doi.org/10.1007/s10266-018-0349-2DOI Listing
July 2018

Clinical complications in the application of polyglycolic acid sheets with fibrin glue after resection of mucosal lesions in oral cavity.

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 06 29;125(6):541-546. Epub 2017 Dec 29.

Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Objectives: Covering open wounds with a polyglycolic acid (PGA) sheet using fibrin glue after resection of oral mucosal lesions is reportedly useful. We focused on clinical complications of this procedure: development of marked granuloma-like neoplasm (GLN) and abnormal postoperative bleeding (APB) on the resected region.

Study Design: The characteristics of 100 cases with PGA sheet application after the resection of oral mucosal lesion were examined retrospectively by the medical records and/or oral photographs at our department between 2010 and 2016.

Results: Our retrospective analysis identified included 8 cases of GLN development and 7 cases of APB. There was a significantly higher risk of GLN development when the PGA sheet was applied to the raw surface of the tongue. There were no immediate APBs, but 4 APBs occurred several hours after surgery. All APB cases involved the tongue.

Conclusions: Both GLNs and APBs are minor complications. Although all cases of GLNs did not involve the recurrence of a tumor, follow-up with incisional or excisional biopsy should be performed. APB in the oral cavity induced by the PGA sheet peeling due to fluctuating adhesive force of the PGA sheets and fibrin glue can sometimes induce life-threatening events.
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http://dx.doi.org/10.1016/j.oooo.2017.12.013DOI Listing
June 2018

Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of rhBMP-2.

PLoS One 2018 18;13(1):e0191099. Epub 2018 Jan 18.

Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation facilitates the clinical use of rhBMP-2 as an alternative strategy for bone engineering.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191099PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773187PMC
February 2018

Oral epithelial cell sheets engraftment for esophageal strictures after endoscopic submucosal dissection of squamous cell carcinoma and airplane transportation.

Sci Rep 2017 12 12;7(1):17460. Epub 2017 Dec 12.

Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial oesophageal squamous cell carcinoma (ESCC). However, post-procedure stricture is common after ESD for widespread tumours, and multiple endoscopic balloon dilation (EBD) procedures are required. We aimed to evaluate the safety and effectiveness of endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets that had been transported by air over a distance of 1200 km in controlling postprocedural oesophageal stricture. Ten patients who underwent complete circular or semicircular ESD for ESCC were transplanted with cell sheets. The safety of the entire process including cell sheet preparation, transport, ESD and cell sheet transplantation was assessed. The incidence of oesophageal stricture, number of EBD sessions, and time until epithelialization were investigated. Each ESD was successfully performed, with subsequent cell sheet engrafting carried out safely. Following cell sheet transplantation, the luminal stenosis rate was 40%, while the median number of EBD sessions was 0. The median post-ESD ulcer healing period was rather short at 36 days. There were no significant complications at any stage of the process. Cell sheet transplantation and preparation at distant sites and transportation by air could be a safe and promising regenerative medicine technology.
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http://dx.doi.org/10.1038/s41598-017-17663-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727129PMC
December 2017

The effect of photodynamic therapy with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma: A series of eight cases.

Photodiagnosis Photodyn Ther 2018 Mar 2;21:176-180. Epub 2017 Dec 2.

Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588 Japan.

Objective: To assess the effect of photodynamic therapy (PDT) with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma (SCC).

Methods: Eight patients who were diagnosed with oral SCC without any metastasis and underwent talaporfin sodium-mediated PDT (t-PDT) were included in this study. Biopsies were performed 4-6 weeks after t-PDT. The clinical response was evaluated using Response Evaluation Criteria in Solid Tumors.

Results: Complete response (CR) was achieved in six of eight cases, and two cases showed partial response (PR) as a clinical outcome of t-PDT. Recurrence occurred in one of the CR cases 9 months after irradiation. The patient underwent tumor resection and no recurrence was found after surgery. The two cases with PR died from the cancer despite additional PDT.

Conclusion: t-PDT is an effective treatment strategy for oral SCC. Talaporfin sodium has an advantage with regard to early elimination from the body compared with porfimer sodium.
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http://dx.doi.org/10.1016/j.pdpdt.2017.11.016DOI Listing
March 2018

Low-risk population among patients with tumor-node-metastasis stage III/IV oral squamous cell carcinoma.

Oncol Lett 2017 Sep 15;14(3):3711-3716. Epub 2017 Jul 15.

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.

A novel system auxiliary to the Union for International Cancer Control classification may allow the prognosis of patients with malignant tumors at similar stages to be predicted, as currently this is challenging. The present study generated a novel system to predict populations at low risk among patients with stage III/IV oral squamous cell carcinoma (OSCC). A total of 41 patients who were diagnosed at stages III/IV OSCC and underwent surgical tumor resection were analyzed. Band-like or follicular lymphocyte infiltration, intraepithelial micro-abscess formation and natural killer (NK) cell infiltration were histopathologically evaluated. Cox's proportional hazards regression model was used to identify prognostic factors, and a set of factors was selected from a combination of those prognostic factors to create a logic covariate model. A logic regression analysis for 41 patients with OSCC revealed that the presence of intraepithelial micro-abscesses and a lower density of NK cells were significantly associated with a favorable prognosis among patients with stage III/IV OSCC. These results suggested that the host innate immune responses, including neutrophil and NK cell infiltrations, are useful for prognostic prediction in patients with advanced malignant tumors.
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http://dx.doi.org/10.3892/ol.2017.6575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587987PMC
September 2017

Histopathological and immunohistochemical study in keratocystic odontogenic tumors: Predictive factors of recurrence.

Oncol Lett 2017 May 24;13(5):3487-3493. Epub 2017 Mar 24.

Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan.

The aim of the present study was to identify the most useful markers for predicting recurrence of keratocystic odontogenic tumors (KCOTs). A total of 65 tumor samples from 63 patients diagnosed with typical parakeratinized cysts and KCOTs between 1992 and 2014 were retrospectively studied. Clinical and histopathological data and treatment modality were reviewed. In addition, the expression profiles of Ki-67, cluster of differentiation (CD)34 and podoplanin were assessed using immunohistochemistry. The association between these factors and the rate of KCOT recurrence was evaluated. The presence of daughter cysts, epithelial islands and high Ki-67, CD34 and podoplanin expression levels were revealed to be associated with tumor recurrence. In particular, univariate analysis revealed that high CD34 expression levels were significantly associated with tumor recurrence (P=0.034), as was conservative surgical treatment (P=0.003). Multivariate analysis revealed that conservative treatment was the greatest independent risk factor for tumor recurrence (odds ratio=13.337; P=0.018). These results suggest that overexpression of CD34 may be a potent predictor of tumor recurrence and radical treatment of the teeth that are in contact with the tumors is recommended in order to prevent tumor recurrence.
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http://dx.doi.org/10.3892/ol.2017.5905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431266PMC
May 2017

Physiological positioning strategy alters condylar position after mandibular ramus sagittal split osteotomies for mandibular prognathism.

Cranio 2018 May 8;36(3):181-188. Epub 2017 Apr 8.

a Department of Regenerative Oral Surgery, Unit of Translational Medicine , Graduate School of Biomedical Sciences, Nagasaki University , Nagasaki , Japan.

Objective: The aim of this study was to elucidate the physiological position of the proximal segment for postoperative jaw movement in patients with mandibular prognathism.

Methods: Twenty-two patients with mandibular prognathism were treated by orthognathic surgery using bilateral mandibular sagittal split ramus osteotomies (SSRO) with a physiological positioning strategy. The skeletal stability was assessed, and the movement of the proximal segment was evaluated by cephalography and computed tomography performed preoperatively, immediately postoperatively, and one year postoperatively.

Results: The patients were divided into two groups: the stable group (SNB relapse <1.5°) and the relapse group (SNB relapse ≥1.5°). In the stable group at one year postoperatively, the average SNB relapse was only 0.29° (7%), the condylar head had moved posteriorly by 0.75 mm, and the proximal segment had rotated counterclockwise by 1.2°.

Conclusion: This new physiological positioning strategy improves the position of the condyle compared with the preoperative position in patients with mandibular prognathism.
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http://dx.doi.org/10.1080/08869634.2017.1314432DOI Listing
May 2018

Soft tissue engineering with micronized-gingival connective tissues.

J Cell Physiol 2018 Jan 3;233(1):249-258. Epub 2017 May 3.

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability.
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http://dx.doi.org/10.1002/jcp.25871DOI Listing
January 2018

Low-serum culture with novel medium promotes maxillary/mandibular bone marrow stromal cell proliferation and osteogenic differentiation ability.

Clin Oral Investig 2017 Dec 16;21(9):2709-2719. Epub 2017 Feb 16.

Department of Oral and Maxillofacial Prosthodontics, Kagoshima University Graduate School of Biomedical Sciences, Kagoshima, Japan.

Objectives: The purpose of this study was to evaluate the effect of low-serum STK2 medium on the isolation and osteogenic differentiation of human maxillary/mandibular bone marrow stromal cells (MBMSCs).

Materials And Methods: Human MBMSCs were obtained from patients undergoing dental implant treatment. These cells were cultured in serum-free medium or STK2 medium containing 1  % fetal bovine serum (low-serum) or α-MEM containing 10  % fetal bovine serum (control). Proliferation on the culture surface, cell surface antigen expression, and mRNA levels of neural crest and osteogenic markers were examined. Alkaline phosphatase assay and Alizarin red staining were used to assess osteogenic differentiation potential. Immunoblotting analysis was performed to detect ERK phosphorylation.

Results: Low-serum and control MBMSCs were positive for CD73, CD90, and CD105 and negative for CD14, CD34, CD45, CD271, and HLA-DR. CD140a was absent in low-serum cells but present in control cells. Low-serum MBMSCs proliferated more than control MBMSCs. After induction of osteogenic differentiation, alkaline phosphatase activity and osteocalcin mRNA levels were higher in low-serum MBMSCs than in control cells, and Alizarin red staining was stronger in low-serum MBMSCs than in control cells. Low-serum culture promoted ERK phosphorylation.

Conclusions: MBMSCs precultured in low-serum medium exhibited a greater cumulative cell number and a higher osteogenic differentiation capacity than those cultured in control medium.

Clinical Relevance: These findings indicate that low-serum STK2 culture might be useful to promote MBMSC proliferation and osteogenic differentiation. This method requires less autologous blood collection for cell expansion than conventional methods, thus reducing the burden on patients.
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http://dx.doi.org/10.1007/s00784-017-2073-7DOI Listing
December 2017

Soft tissue changes after a mandibular osteotomy for symmetric skeletal class III malocclusion.

Odontology 2017 Jul 31;105(3):375-381. Epub 2016 Oct 31.

Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.

The soft tissue profile is crucial to esthetics after orthognathic surgery. The aim of this study was to assess the soft tissue changes of the subnasal and submental regions more than 1 year after a sagittal split ramus osteotomy (SSRO) in patients with skeletal class III malocclusion. A total of 22 patients with mandibular prognathism were included in this study. Patients had lateral cephalograms before and more than 1 year after they underwent an isolated SSRO. Soft and hard tissue changes were assessed using the lateral cephalograms. The lower lip, labiomenton, and soft tissue menton moved posteriorly by 85, 89, and 88% compared with the corresponding hard tissue, and the movement of the soft tissue B point and the top of the chin nearly reflected the displacement of the hard tissues, at 96 and 99%, respectively. The labiomenton, stomions, and naso-labial angles were changed after the mandibular set-back and the changes in these angles correlated with either the width of the soft tissue or skeletal displacement. The naso-labial angle could be altered even if an isolated mandibular osteotomy is performed. Changes to the stomions and naso-labial angles were affected by hard tissue movement, while changes to the labiomental angle were affected by the width of the soft tissue after the mandibular osteotomy. It is important to create an accurate preoperative prediction of the esthetic outcomes after a mandibular osteotomy by considering the interrelations between the hard and soft tissues.
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http://dx.doi.org/10.1007/s10266-016-0280-3DOI Listing
July 2017

Efficacy of freeze-dried platelet-rich plasma in bone engineering.

Arch Oral Biol 2017 Jan 15;73:172-178. Epub 2016 Oct 15.

Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8102, Japan. Electronic address:

Objective: Platelet-rich plasma (PRP) is typically isolated and applied immediately after preparation, making it both a time- and labor-intensive addition to the operative procedure. Thus, it would be convenient if PRP could be preserved. We evaluated the efficacy of freeze-dried PRP (FD-PRP), as compared with freshly isolated PRP (f-PRP) for bone engineering.

Design: FD-PRP was prepared by lyophilization of f-PRP and was subsequently preserved at -20°C for one month. It was then rehydrated with an equal or 1/3 amount of distilled water (×1FD-PRP, ×3FD-PRP, respectively), and we assessed its gelation properties and the release of growth factors (PDGF-BB, TGF-β1, and VEGF). We also examined the bone forming ability with onlay-grafting on mice calvaria using β-TCP granules as a scaffold.

Results: FD-PRP showed comparable gelation as f-PRP. In terms of growth factor release,×1FD-PRP released identical concentrations of PDGF-BB and TGF-β1 to f-PRP, while ×3FD-PRP released approximately 3-fold concentrations when compared with f-PRP. In vivo, ×1FD-PRP promoted identical levels of the bone formation as f-PRP, and ×3FD-PRP induced more abundant bone formation.

Conclusions: These results suggest that f-PRP can be stored without functional loss by freeze-drying and the concentration of PRP may improve its efficacy in bone engineering.
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http://dx.doi.org/10.1016/j.archoralbio.2016.10.006DOI Listing
January 2017