Tsuyoshi Takato

Tokyo Medical University, Edo, Tōkyō, Japan

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Publications (314)656.7 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Previously, we reported that the transcription factor Nanog, which maintains the self-renewal of embryonic stem cells (ESCs), promotes the osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 through a genome reprogramming process. In the present study, to clarify the mechanism underlying the multipotency of mesenchymal stem cells (MSCs) and to develop a novel approach to bone regenerative medicine, we attempted to identify the downstream effectors of Nanog in promoting osteogenic differentiation of mouse mesenchymal cells. We demonstrated that Runx1 and Runx3 are the downstream effectors of Nanog, especially in the early and intermediate osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2.
    06/2015; 17(3):227-234. DOI:10.1089/cell.2014.0059
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    ABSTRACT: The nasolabial cyst, a rare lesion involving the soft tissues of the maxillofacial region, commonly occurs in middle-aged females. These cysts usually present as soft, fluctuating growths in the sublabial folds, and are seen as swellings between the upper lip and nostril. Modern radiographic methods aid in the diagnosis of these cysts. There is an ongoing debate regarding the origin of nasolabial cysts, as there are two schools of thought: some believe that these cysts originate from fissural cysts, while others are of the opinion that they originate from remnants of the nasolacrimal groove. Herein, we present a rare case of a nasolabial cyst occurring in a 13-year-old girl treated for unilateral cleft lip and alveolus, using bone grafts nearly 5 years after lip and nose revision surgery. This contradicts with the previous theory regarding the origin of nasolabial cysts from fissural cysts. Despite indications that the cyst may have originated from remnants of the nasolacrimal groove, in the present study, trauma, infection or other unknown factors may have contributed to the pathogenesis of the nasolabial cyst.
    05/2015; DOI:10.1016/j.ajoms.2015.04.009
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    ABSTRACT: Occurrences of aneurysm caused by intraoral inflammation or infection are very rare. Osseous dysplasias (ODs), the most common fibro-osseous lesions (FOLs), occur in the jaw. However, osseous lesion very rarely occurs in association with impacted tooth. We present here the case of a 22-year-old female who developed aneurysm in the cavernous region of the internal carotid artery (ICA) because of the infection of the maxillary OD with impacted and semi-impacted teeth. The aneurysm was later confirmed by contrast enhanced magnetic resonance imaging (MRI). The ICA trapping was performed under general anesthesia, and postoperative magnetic resonance angiography (MRA) confirmed disappearance of aneurysm. Approximately 2 months after the surgery, we performed left maxilla tumor excision under general anesthesia; the patient showed satisfactory progress after the excision. Since inflammation/infection of the maxilla may lead to aneurysm as found in this case, we recommend physicians to pay serious attention in such cases to prevent rupture of aneurysm.
    05/2015; DOI:10.1016/j.ajoms.2015.04.007
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    ABSTRACT: Human pluripotent cells are promising for treatment for kidney diseases, but the protocols for derivation of kidney cell types are still controversial. Kidney tissue regeneration is well confirmed in several lower vertebrates such as fish, and the repair of nephrons after tubular damages is commonly observed after renal injury. Even in adult mammal kidney, renal progenitor cell or system is reportedly presents suggesting that adult stem-like cells in kidney can be practical clinical targets for kidney diseases. However, it is still unclear if kidney stem cells or stem-like cells exist or not. In general, stemness is defined by several factors such as self-renewal capacity, multi-lineage potency and characteristic gene expression profiles. The definite use of stemness may be obstacle to understand kidney regeneration, and here we describe the recent broad findings of kidney regeneration and the cells that contribute regeneration.
    03/2015; 7(2):490-494. DOI:10.4252/wjsc.v7.i2.490
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    ABSTRACT: Mammary analog secretory carcinoma (MASC) is a newly described rare malignancy of the salivary glands characterized by an ETS variant 6 (ETV6)–neurotrophic tyrosine kinase receptor type 3 (NTRK3) fusion gene (EN fusion gene).
    02/2015; 135. DOI:10.1016/j.ijscr.2015.02.011
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    ABSTRACT: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life threatening severe cutaneous adverse reactions, primarily caused by drugs and infection. Most of the cases of SJS are predominantly drug related. Drugs including antibacterial sulfonamides, non-steroidal anti-inflammatory drugs (NSAIDs) and anti-epileptic drugs have been identified to cause SJS/TEN. We report a case of 35 year old male, road accident victim, who suffered from mandibular fracture and a splenic injury, admitted to our hospital. Following the splenic embolization in Radiology Department he was administered cefazolin sodium and diclofenac sodium. The patient developed skin lesions characteristic of SJS, which was confirmed by skin biopsy. From the course of the skin lesions and its relation to diclofenac sodium administration and discontinuation, the drug was suspected to have caused SJS. The cefazolin sodium and diclofenac sodium were stopped one after another. Patient was successfully treated with prednisolone and was issued with drug card to prevent further attack of SJS by the same drug. We report the present case, in order to raise awareness that frequently prescribed NSAIDs diclofenac sodium has potential to cause rare skin disorder like SJS and prepare physician for the early intervention of any such future incidence.
    01/2015; 27(1). DOI:10.1016/j.ajoms.2013.05.016
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    ABSTRACT: Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.
    Biomedical Research 01/2015; 36(3):179-86. DOI:10.2220/biomedres.36.179 · 1.10 Impact Factor
  • 01/2015; 1(1):e000068-e000068. DOI:10.1136/rmdopen-2015-000068
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    ABSTRACT: Odontogenic infection in immunocompromised patients tends to extend systemically beyond the oral cavity. Our case report presents a patient with sepsis due to a Streptococcus constellatus (S. constellatus) odontogenic infection in a 64-year-old-immunocompromised woman with Cogan's syndrome. She had been suffering from chronic mandibular osteomyelitis which was thought to have been caused by dental caries and/or chronic periodontitis with furcation involvement of the left mandibular first molar. We suspect that the acute symptoms of the chronic osteomyelitis due to S. constellatus led to the systemic infection. This infection could be accelerated by the use of a corticosteroid and an alendronate. This is the first report which represents the potential association between odontogenic infection and Cogan's syndrome.
    11/2014; 2014. DOI:10.1155/2014/793174
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    ABSTRACT: Severe tracheomalacia is a life-threatening disease, but symptoms usually improve with growth. The aims of this study were to investigate how slow release basic-Fibroblast Growth Factor (b-FGF) acts on tracheal cartilage, and whether growth-promoted trachea is more resistant against an increase in externally-applied pressure.Methods Biodegradable gelatin hydrogel sheets soaked in 10 μl of distilled water (sham) or 0.5 or 5 μg/10 μl of b-FGF solution were inserted behind the cervical trachea of three-week-old male Wistar rats. The cervical trachea was harvested 4 weeks later. Extratracheal pressure was increased from 0 to 40 cmH2O in a chamber, while video-recording the internal lumen. The luminal area at each pressure was expressed as a proportion to that at 0 cmH2O. The amounts of collagen type II and glycosaminoglycan were measured by ELISA.ResultsThe luminal areas at 40 cmH2O in the control (no intervention), sham, and each of the b-FGF groups were 0.65, 0.62, 0.72, and 0.73, respectively. The amounts of collagen type II and glycosaminoglycan in each group were 127, 136, 193, 249 μg/mg, respectively, and 15, 16, 19, 33 μg/mg, respectively. There were significant differences between the control group and the FGF 5 group (P = 0.02, 0.01, 0.01, for luminal area, collagen, and glycosaminoglycan, respectively).Conclusion5 μg of slow-release b-FGF promotes matrix production (collagen type II and glycosaminoglycan). The growth-enhanced trachea was more resistant to collapse, suggesting that slowly released b-FGF might be useful in patients with severe tracheomalacia.
    Journal of Pediatric Surgery 11/2014; 50(2). DOI:10.1016/j.jpedsurg.2014.11.012 · 1.31 Impact Factor
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    ABSTRACT: Hedgehog (Hh) signaling plays important roles in various development processes. This signaling is necessary for osteoblast formation during endochondral ossification. In contrast to the established roles of Hh signaling in embryonic bone formation, evidence of its roles in adult bone homeostasis is not complete. Here we report the involvement of Gli1, a transcriptional activator induced by Hh signaling activation, in postnatal bone homeostasis under physiological and pathological conditions. Skeletal analyses of Gli1+/- adult mice revealed that Gli1 haploinsufficiency caused decreased bone mass with reduced bone formation and accelerated bone resorption, suggesting an uncoupling of bone metabolism. Hh-mediated osteoblast differentiation was largely impaired in cultures of Gli1+/- precursors, and the impairment was rescued by Gli1 expression via adenoviral transduction. In addition, Gli1+/- precursors showed premature differentiation into osteocytes and increased ability to support osteoclastogenesis. When we compared fracture healing between wild-type and Gli1+/- adult mice, we found that the Gli1+/- mice exhibited impaired fracture healing with insufficient soft callus formation. These data suggest that Gli1, acting downstream of Hh signaling, contributes to adult bone metabolism, in which this molecule not only promotes osteoblast differentiation but also represses osteoblast maturation toward osteocytes to maintain normal bone homeostasis.
    PLoS ONE 10/2014; 9(10):e109597. DOI:10.1371/journal.pone.0109597 · 3.53 Impact Factor
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    ABSTRACT: [Background] A gelatin sponge with slowly releasing basic fibroblast growth factor (b-FGF) enhances chondrogenesis. This study investigated the optimal amount of basic fibroblast growth factor (b-FGF) in gelatin sponges to fabricate engineered cartilage. [Material and Methods] b-FGF (0, 10, 100, 500, 1000 and 2000μg/cm3)-impregnated gelatin sponges incorporating β-tri-calcium-phosphate (β-TCP) were produced. Chondrocytes were isolated from the auricular cartilage of C57B6J mice and expanded. The expanded auricular chondrocytes (10x106cells/cm3) were seeded onto the gelatin sponges, which served as scaffolds. The construct assembly was implanted in the subcutaneous space of mice through a syngeneic fashion. Thereafter, constructs were retrieved at 2, 4 or 6 weeks. [Results]Morphology: The size of implanted constructs was larger than the size of the scaffold with 500, 1000 and 2000μg/cm3 b-FGF-impregnated gelatin sponges incorporating β-TCP at 4 weeks and 6 weeks after implantation.  The weight of the constructs increased roughly proportional to the increase in volume of the b-FGF-impregnated scaffold at 2weeks, 4weeks and 6weeks after implantation, except in the 2000μg/cm3 b-FGF-impregnated constructs group. Histological examination: Extracellular matrix in the center of the constructs was observed in gelatin sponges impregnated with more than 100μg/cm3 b-FGF at 4 weeks after implantation. The areas of cells with abundant extracellular matrix were positive for cartilage-specific marker type 2 collagen in the constructs. ○4Protein assay: Glycosaminoglycan and collagen type 2 expression were significantly increased at 4 and 6 weeks upon implantation of gelatin sponges impregnated with more than 100μg/cm3 b-FGF. At 6weeks after implantation, the ratio of type 2 collagen to type 1 collagen in constructs impregnated with 100μg/cm3 or more b-FGF was higher than that in mice auricular cartilage. [Conclusion] Gelatin sponges impregnated with more than 100μg/cm3 b-FGF incorporating β-TCP with chondrocytes (10x106cells/cm3) can fabricate engineered cartilage at 4 weeks after implantation.
    Tissue Engineering Part A 10/2014; 21(3-4). DOI:10.1089/ten.TEA.2013.0655 · 4.70 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):430-430. DOI:10.1158/1538-7445.AM2014-430 · 9.28 Impact Factor
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    ABSTRACT: We used a piece of costal cartilage as a cartilaginous strut to correct the upturned nasal tip in patients with bilateral cleft lip. The grafted cartilage provides more definition of the tip and improves the obtuse nasolabial angle. Neither the septal cartilage nor the ear cartilage has enough strength to shape the tip. This method of correction has consistently produced favorable, long-lasting results in adults and has improved the contour of the nasal tip in younger patients.
    Journal of Craniofacial Surgery 09/2014; 25(5):e443-e445. DOI:10.1097/SCS.0000000000000954 · 0.68 Impact Factor
  • Journal of Oral and Maxillofacial Surgery 09/2014; 72(9):e132-e133. DOI:10.1016/j.joms.2014.06.238 · 1.28 Impact Factor
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    ABSTRACT: Pleomorphic adenoma is the most common benign parotid gland tumor. Although its local recur-rence rate is known to be high, the recurrence extending to the cervical region is rare. Here we report a case of a young female (25 years old) with pleomorphic adenoma of the parotid gland which showed multiple recurrences through facial to cervical regions over a span of eight years. We also discuss how this benign tumor with a high recurrence rate has been treated in other cases, and how it should be treated.
    Open Journal of Stomatology 08/2014; 4(4):441-445. DOI:10.4236/ojst.2014.49059
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    ABSTRACT: Purpose Our objective was to investigate the feasibility of engineering cartilage on the esophagus layer and outside the esophagus. Moreover, we investigated the feasibility of tracheoplasty with cartilage engineered on the esophagus in rabbits. Methods Chondrocytes were isolated from auricular cartilages. 1. Engineered cartilage formation by histological findings on/into the esophageal layer was compared with that of injectable scaffold and preformed scaffold with chondrocytes. 2. Chondrocytes adhered to gelatin + vicryl mesh™ and b-FGF, were implanted on the outer esophageal surface. Four weeks after seeding, we found that cartilage was implanted in the midposterior portion of the cervical trachea (n = 5), and it was retrieved 8 weeks after seeding. Results 1. A gelatin sponge incorporating β-TCP with vicryl mesh™ showed the best performance for fabricating engineered cartilage on the outer side of the esophagus. 2. Two of 5 rabbits died due to obstructed esophagus. Cartilage engineered outside the esophagus by a composite scaffold as the main material in the gelatin sponge, maintained the airway structure for up to 1 month after implantation. Tracheal epithelial regeneration occurred in the internal lumen of this engineered cartilage. Conclusion Tracheoplasty with cartilage engineered outside the esophagus may be useful for reconstructing airways.
    Journal of Pediatric Surgery 08/2014; 50(7). DOI:10.1016/j.jpedsurg.2014.07.005 · 1.31 Impact Factor
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    ABSTRACT: Previous reports suggest that the most common location of the odontomas are in the maxilla. Among the ectopic odontoma, the nasal ectopic odontomas are rare, and are usually asymptomatic. Here, we present a rare case of an ectopic complex odontoma in the lower nasal turbinate causing nasal obstruction and bleeding, which was removed surgically. A 33-year-old male patient presented to our hospital with chief symptoms of nasal obstruction and bleeding from the nose. The Computed Tomography (CT) image of head and neck showed an irregular radio opaque mass in the lower nasal turbinate. The endoscopic examination revealed part of the tumor resembling toothlet. From the above findings, clinical diagnosis of odontoma was made. Histological examination of the mass confirmed the diagnosis of complex odontoma. The symptoms of obstruction and bleeding was averted by surgical removal of the mass.
    07/2014; 26(3):347–350. DOI:10.1016/j.ajoms.2013.02.002
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    ABSTRACT: In this study, we developed a new method to stimulate osteogenic differentiation in tissue-nonspecific alkaline phosphatase (TNAP)-positive cells liberated from human induced pluripotent stem cells (hiPSCs)-derived embryoid bodies (EBs) with 14 days long TGF-β/IGF-1/FGF-2 treatment. TNAP is a marker protein of osteolineage cells. We analyzed and isolated TNAP-positive and E-cadherin-negative nonepithelial cells by fluorescence-activated cell sorting. Treating the cells with a combination of transforming growth factor (TGF)-β, insulin-like growth factor (IGF)-1, and fibroblast growth factor (FGF)-2 for 14 days greatly enhanced TNAP expression and maximized expression frequency up to 77.3%. The isolated cells expressed high levels of osterix, which is an exclusive osteogenic marker. Culturing these TNAP-positive cells in osteoblast differentiation medium (OBM) led to the expression of runt-related transcription factor 2, type I collagen, bone sialoprotein, and osteocalcin (OCN). These cells responded to treatment with activated vitamin D3 by upregulating OCN. Furthermore, in OBM they were capable of generating many mineralized nodules with strong expression of receptor activator of NF-kappaB ligand and sclerostin (SOST). Real-time RT-PCR showed a significant increase in the expression of osteocyte marker genes, including SOST, neuropeptide Y, and reelin. Scanning electron microscopy showed dendritic morphology. Examination of semi-thin toluidine blue-stained sections showed many interconnected dendrites. Thus, TNAP-positive cells cultured in OBM may eventually become terminally differentiated osteocyte-like cells. In conclusion, treating hiPSCs-derived cells with a combination of TGF-β, IGF-1, and FGF-2 generated TNAP-positive cells at high frequency. These TNAP-positive cells had a high osteogenic potential and could terminally differentiate into osteocyte-like cells. The method described here may reveal new pathways of osteogenesis and provide a novel tool for regenerative medicine and drug development.
    PLoS ONE 06/2014; 9(6):e99534. DOI:10.1371/journal.pone.0099534 · 3.53 Impact Factor
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    ABSTRACT: Pluripotent stem cells are a promising tool for mechanistic studies of tissue development, drug screening, and cell-based therapies. Here, we report an effective and mass-producing strategy for the stepwise differentiation of mouse embryonic stem cells (mESCs) and mouse and human induced pluripotent stem cells (miPSCs and hiPSCs, respectively) into osteoblasts using four small molecules (CHIR99021 [CHIR], cyclopamine [Cyc], smoothened agonist [SAG], and a helioxanthin-derivative 4-(4-methoxyphenyl)pyrido[4',3':4,5]thieno[2,3-b]pyridine-2-carboxamide [TH]) under serum-free and feeder-free conditions. The strategy, which consists of mesoderm induction, osteoblast induction, and osteoblast maturation phases, significantly induced expressions of osteoblast-related genes and proteins in mESCs, miPSCs, and hiPSCs. In addition, when mESCs defective in runt-related transcription factor 2 (Runx2), a master regulator of osteogenesis, were cultured by the strategy, they molecularly recapitulated osteoblast phenotypes of Runx2 null mice. The present strategy will be a platform for biological and pathological studies of osteoblast development, screening of bone-augmentation drugs, and skeletal regeneration.
    Stem Cell Reports 06/2014; 2(6):751-60. DOI:10.1016/j.stemcr.2014.04.016

Publication Stats

3k Citations
656.70 Total Impact Points


  • 1986–2015
    • Tokyo Medical University
      • • Department of Oral and Maxillofacial Surgery
      • • Department of Plastic and Reconstructive Surgery
      Edo, Tōkyō, Japan
  • 1985–2015
    • The University of Tokyo
      • • Department of Tissue Engineering
      • • Department of Oral-Maxillofacial Surgery, Dentistry and Orthodontics
      • • Division of Sensory and Motor System Medicine
      • • Department of General Surgery
      • • Division of Surgery
      Tōkyō, Japan
  • 2009
    • Tsurumi University
      • School of Dental Medicine
      Yokohama, Kanagawa, Japan
  • 2007
    • Japan Society for the Promotion of Science
      Edo, Tōkyō, Japan
  • 2002–2005
    • Kitasato University
      Edo, Tōkyō, Japan
  • 2004
    • Stanford University
      Palo Alto, California, United States
  • 2000
    • Saitama Medical University
      Saitama, Saitama, Japan
  • 1998
    • Teikyo University
      Edo, Tōkyō, Japan
  • 1988–1997
    • Shizuoka Hospital
      Sizuoka, Shizuoka, Japan
  • 1992
    • SickKids
      • Division of Plastic Surgery
      Toronto, Ontario, Canada