Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

Objective: We previously reported that secretomes from human bone marrow-derived mesenchymal stem cells (MSC-CM) have a strong potential to accelerate bone regeneration. The most important initial step for bone regeneration is osteoprogenitor cell migration to bone defects. We hypothesized that MSC: CM enhance the migration of endogenous stem cells earlier to the local lesioned part. In this study
we investigated the potential of MSCCM to induce in vivo early bone regeneration by accelerating cell migration in a rat calvarial bone defect model. Materials and methods: Cytokine array analysis was performed to assess the types of cytokines included in MSC-CM. Bone defects (5 mm in diameter) were created in the calvarial bones of rats, and the damaged areas were implanted with atelocollagen suspended in MSC-CM or phosphate buffered saline. After 2 and 4 weeks, radiographic and histological analyses were performed. Furthermore, rat mesenchymal stem cells (rMSCs) were labeled with the lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR), and the rats were photographed at various times after injection of the DiR-labeled rMSCs using in vivo imaging. Results: MSC-CM contained many factors with respect to cell migration and tissue regeneration. Bone regeneration in rat calvaria was observed earliest in the MSC-CM implantation group. Migration of the labeled rMSCs from the tail toward the calvaria, where MSC-CM was implanted, was observed during the first 24 h after injection in the MSC-CM implantation group using in vivo imaging. Immunohistochemistry also indicated early cell migration. Conclusion: MSC-CM enhanced the migration of endogenous stem cells facilitating earlier bone regeneration.

DOI： 10.1016/j.ajoms.2018.04.002

Web of Science

Scopus

Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. METHODS: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. RESULTS: The concentrations of IGF-1, VEGF, and TGF-β1 in MSC-CM were 1515.6 ± 211.8 pg/mL, 465.8 ± 108.8 pg/mL, and 339.8 ± 14.4 pg/mL, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. CONCLUSIONS: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

DOI： 10.1186/s40902-017-0106-4

Web of Science

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVE: This clinical study was undertaken to evaluate the safety of use of the secretome of bone marrow-derived mesenchymal stem cells (MSC-CM) for maxillary sinus floor elevation (SFE). MATERIALS AND METHODS: MSC-CM was prepared from conditioned medium from human bone marrow-derived MSCs. Six partially edentulous patients were enrolled in the study. MSC-CM was mixed with porous beta-tricalcium phosphate (β-TCP) and implanted in 4 patients (experimental group), whereas only β-TCP was implanted in the other 2 patients (control group). Six months after SFE, bone biopsies and histological assessments were performed. RESULTS: Bone formation was clinically confirmed in all cases. Although Hounsfield units in computed tomography images were not significantly different between the groups, histological analysis revealed a significant difference in newly formed bone area between the groups. In particular, bone volume in the center of the augmented area was significantly greater in the MSC-CM group. Newly formed bone consisted of lamellar bone in the MSC-CM group but woven bone in the β-TCP group. CONCLUSION: The secretome of bone marrow-derived mesenchymal stem cells (MSC-CM) was used safely and has great osteogenic potential for regenerative medicine of bone.

DOI： 10.1097/ID.0000000000000618

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

OBJECTIVES: We previously reported that conditioned medium from cultures of bone marrow-derived mesenchymal stem cells have strong potential to accelerate bone regeneration. We now examine in vitro and in vivo a defined cytokine cocktail that mimics the effects of conditioned medium on bone regeneration. MATERIALS AND METHODS: A cocktail of recombinant human insulin-like growth factor-1, vascular endothelial growth factor-A and transforming growth factor-β1 was prepared at concentrations similar to those in conditioned medium. Conversely, these cytokines were depleted from conditioned medium, and the effects of the cocktail, the conditioned medium and the cytokine-depleted conditioned medium on bone regeneration were evaluated in vitro and in vivo. RESULTS: The cytokine cocktail and conditioned medium enhanced cell migration, tube formation, and expression of osteogenic and angiogenic genes. Depletion of cytokines significantly decreased the effects of conditioned medium in vitro. Similarly, the cytokine cocktail and conditioned medium, but not cytokine-depleted medium, increased bone regeneration in damaged rat calvarial bone. Immunohistochemistry indicated that the cytokine cocktail and conditioned medium strongly enhanced recruitment of endogenous stem cells and endothelial cells. CONCLUSIONS: The data indicate that the cytokine cocktail and conditioned medium enhance the migration of stem cells and endothelial cells to damaged bone, and elicit osteogenesis and angiogenesis.

DOI： 10.1111/cpr.12333

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Secretomes in the conditioned media from human mesenchymal stem cells (MSC-CM) were previously demonstrated to promote periodontal tissue regeneration. By mixing insulin-like growth factor-1, vascular endothelial growth factor-A, and transforming growth factor-β1 which were included in MSC-CM, we made the cytokine cocktail (CC) mimicking MSC-CM, and then evaluated its efficacy on periodontal tissue regeneration. In vitro, CC promoted the migration of dog bone marrow-derived stem cells and periodontal ligament cells, and the tube formation of human umbilical vein endothelial cells. In vivo, class II furcation defects were surgically created at premolars in dogs. After 4 weeks of vinylpolysiloxane-induced inflammation, defects were filled with or without CC mixed in hydroxypropyl cellulose, or enamel matrix derivative (EMD). After 8 weeks, periodontal tissues were evaluated histologically and immunohistochemically. CC showed promotional effects on angiogenesis and formation of new bone and cementum. Osteogenesis by CC was greater than that by EMD and cementogenesis by CC was as well as that by EMD. CC may be promising for periodontal tissue regeneration.

DOI： 10.1016/j.bbrc.2017.01.065

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：The Japanese Society for Temporomandibular Joint  

<p>Therapeutic exercise increases range of motion, decreases pain, and shortens the duration of symptoms. However, few studies have assessed the effectiveness of therapeutic exercise by using quantitative methods. In this study, we prescribed a range of temporomandibular joint motion exercises involving both passive exercises performed by a dentist and self-traction therapy performed by the patient, and evaluated the short-term effectiveness of the treatment in patients with temporomandibular joint anterior disc displacement without reduction.</p><p>We enrolled 45 patients who had moderate or severe TMJ function. We asked them to perform therapeutic exercises and evaluated their clinical symptoms (maximum opening distance, pain at rest, pain on motion, pain on mastication, and degree of difficulty in performing activities of daily living) at the first visit and at the first follow-up visit approximately 2 weeks later.</p><p>The results demonstrated statistically significant improvements in maximum opening distance, pain on motion, pain on mastication and degree of difficulty in performing activities of daily living (p<0.001). The positive outcomes were considered the result of improvements in range of joint motion and expansion of the joint cavity, resulting in smoother movement of the condylar translation. The results of this study suggest that our therapeutic exercise program is a potentially beneficial conservative treatment for the short-term reduction of symptoms accompanying temporomandibular joint anterior disc displacement without reduction.</p>

DOI： 10.11246/gakukansetsu.28.126

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

DOI： 10.1089/scd.2015.0104

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本顎関節学会  

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

Language：Japanese   Publisher：(一社)日本有病者歯科医療学会  

Language：Japanese   Publisher：(一社)日本口腔診断学会  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本顎関節学会  

運動療法は、施術直後より関節可動域を増大し、疼痛を早期に軽減させ病悩期間を短縮するものの、その効果について定量的な評価を行った研究は少ない。本研究では、術者が行う顎関節可動化療法と患者が行う自己牽引療法を1つの運動療法プログラムとして捉え、非復位性関節円板前方転位症例に実施した際の短期的治療効果を検討した。顎関節機能に中等度以上の障害が認められた45例を対象として運動療法を施行し、初診時とその約2週間後の初回再来時における臨床症状(最大開口域、安静時痛、開閉口時痛、咀嚼時痛および日常生活支障度)について評価した。その結果、最大開口域、開閉口時痛、咀嚼時痛および日常生活支障度において有意な改善を認めた(p&lt;0.001)。これら症状の改善は、運動療法により関節可動域が改善され、関節腔が拡大されることで下顎頭の動きが改善したものと考える。したがって、本運動療法プログラムは、非復位性関節円板前方転位に伴う諸症状を短期間に軽減させる有効な保存療法になる可能性が示唆された。(著者抄録)

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