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1.
Bull Tokyo Dent Coll ; 62(1): 49-54, 2021 Mar 13.
Article in English | MEDLINE | ID: mdl-33583881

ABSTRACT

An ameloblastic fibroma (AF) is a proliferative mixed tumor which includes components of both odontogenic epithelium and mesenchymal tissue. It is a relatively rare neoplasm, accounting for approximately only 1.5-4.5% of odontogenic tumors. This case report describes an AF that occurred in the mandibular anterior tooth region in a 9-year-old girl who presented with the chief complaint of swelling in the left mandibular anterior tooth region. Intraoral examination revealed a swelling along the labial gingiva, extending from the left mandibular lateral incisor region to the left mandibular canine. Upon palpation, the swelling appeared to comprise a hard tissue. Computed tomography revealed a supernumerary impacted tooth; soft tissue density in the bone surrounding the region extending from the left mandibular lateral incisor to the left mandibular canine; labial bone expansion; and thinning of the labial cortical bone. A biopsy was performed under local anesthesia and the lesion subsequently diagnosed as an AF. Tumor resection and extraction of the supernumerary impacted tooth were carried out under general anesthesia. At 2 years postoperatively the prognosis is good. Although relapse with an AF is rarer than that with an ameloblastoma, strict follow-up is required, as malignant transformation to an ameloblastic fibrosarcoma has been reported in relapsed cases.


Subject(s)
Ameloblastoma , Fibroma , Mandibular Neoplasms , Odontogenic Tumors , Tooth, Impacted , Child , Female , Humans , Mandibular Neoplasms/diagnostic imaging , Mandibular Neoplasms/surgery , Odontogenic Tumors/diagnostic imaging , Odontogenic Tumors/surgery
2.
Bull Tokyo Dent Coll ; 61(1): 53-60, 2020 Mar 12.
Article in English | MEDLINE | ID: mdl-32074588

ABSTRACT

An extremely rare case of fibrolipoma in the hard palate is presented and discussed with reference to the literature. An 85-year-old woman visited the Tokyo Dental College Chiba hospital in September 2016 with the chief complaint of a mass in the hard palate. The patient had first become aware of this mass several years earlier. An examination at another hospital in June 2009 resulted in a clinical diagnosis of lipoma. Regular examinations followed every 6 months until September 2014, at which time she stopped attending these appointments because there was no change. In August 2016, however, the patient realized that the tumor was increasing in size. Although there was no pain, awareness of a foreign body in the oral cavity when eating or talking was increasing, so she decided to visit our clinic for detailed examination and treatment. At this point, the mass extended from the center to the left side of the hard palate. It measured 15 mm along the major axis, and had a clear border; nearly spherical, its surface was smooth and glossy, and was of a slightly yellowish color. The mass was painless, elastic, and soft. Computed tomography and magnetic resonance imaging revealed a tumorous lesion. Based on a clinical diagnosis of lipoma, it was subsequently excised under general anesthesia in January 2017. The tumor lay under the palatal mucosa, extending from the center to the left side of the hard palate. It was surrounded by a single-layered membranous structure, and had not adhered to the surrounding tissues. Healthy palatal mucosa and periosteum were also removed en bloc with the tumor within a safety margin of approximately 5 mm. No pressure absorption of palatine bone was seen. Histopathologically, proliferation of mature adipose tissue was observed. This was surrounded by a thin, single-layer membrane within the subepithelial connective tissue, which was covered by stratified squamous epithelium. Proliferation of fibrotic connective tissue was seen between the adipocytes. The final diagnosis was fibrolipoma. To date, at 18 months postoperatively, no recurrence has been observed and progress has been satisfactory.


Subject(s)
Lipoma , Palate, Hard , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging , Tokyo , Tomography, X-Ray Computed
3.
Bull Tokyo Dent Coll ; 60(1): 29-37, 2019 Feb 28.
Article in English | MEDLINE | ID: mdl-30700642

ABSTRACT

Oral exfoliative cytology is now used by general practitioners in Japan to screen for oral cancer. With conventional cytology, however, the number of cells that can be sampled is small. Moreover, cell deformation and piling of cells when preparing specimens has been reported. The purpose of this study was to compare conventional and liquid based cytology (LBC), which has been employed with increasing frequency in recent years. We believe that identifying potential pitfalls in oral exfoliative cytology will help improve diagnostic accuracy. A total of 153 patients with tongue squamous cell carcinoma who were diagnosed and treated initially at our hospital between January 2000 and December 2010 were included. Of these, 124 underwent conventional cytology, while the remaining 29 underwent LBC. Histopathological and clinical findings were used as criteria. Conventional cytology yielded a positive rate of 54.8% and LBC 79.3%, while values of 28.2% and 13.8% were obtained for a suspected positive rate, respectively. Liquid based cytology yielded a significantly higher percentage of accurate diagnoses and fewer suspected positives (p<0.05) in cases clinically classified as endophytic and those classified as ulcerative in terms of clinical growth pattern. No significant difference was observed between conventional cytology and LBC in cases of an infiltrative growth pattern, however.The present results suggest that LBC is superior to conventional cytology in achieving an accurate diagnosis based on oral exfoliative cytology. The present findings also suggest that exophytic type, and especially leukoderma type clinical growth patterns constitute pitfall cases in oral exfoliative cytology.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Cytological Techniques/methods , Early Detection of Cancer/methods , Tongue Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Young Adult
4.
Bull Tokyo Dent Coll ; 59(3): 193-200, 2018.
Article in English | MEDLINE | ID: mdl-30224613

ABSTRACT

Verruciform xanthoma (VX), a papillary or wart-like lesion of the mucosa, is histopathologically characterized by papillary projection of the epithelium and an aggregation of foam cells in the lamina propria. Here, we describe a case of VX in the posterior mandibular gingiva, initially suspected to be a benign lesion based on clinical findings and cytology prior to an excisional biopsy. The patient was a 62-year-old man who had visited a local dentist approximately 1 year earlier, presenting with a white lesion in the left posterior mandibular gingiva that resisted removal by scraping. The lesion was left untreated as there were no subjective symptoms. Thereafter, the surface of the lesion roughened and the patient was referred to our department for a comprehensive examination. A circumscribed, granular mass, 15-mm in diameter, with a red and white surface was observed in the left posterior mandibular buccal gingiva. Exfoliative cytology was performed. The diagnosis was a class III lesion. Excisional biopsy was performed under local anesthesia. Histopathological examination led to a diagnosis of VX. At 1 year postoperatively, the patient is making satisfactory progress without recurrence. Verruciform xanthoma is difficult to diagnose preoperatively, and is commonly resected under a clinical diagnosis of papilloma or benign tumor. A benign lesion was also initially suspected in the present case and cytological analysis performed to confirm absence of malignancy. The lesion could not be diagnosed as VX preoperatively. Verruciform xanthoma can be over-diagnosed based solely on cytological examination because it often involves cellular atypia reflecting its characteristic extension of rete pegs and keratinization of surface cells, indicating the need for care in arriving at a definitive diagnosis.


Subject(s)
Gingival Diseases/pathology , Xanthomatosis/pathology , Gingival Diseases/surgery , Humans , Male , Mandible/surgery , Middle Aged , Xanthomatosis/surgery
6.
Bull Tokyo Dent Coll ; 58(3): 187-191, 2017.
Article in English | MEDLINE | ID: mdl-28954954

ABSTRACT

Conversion disorder is a condition in which psychological stress in response to difficult situations manifests as physical symptoms. Here, we report a case of postoperative coma due to conversion disorder in an elderly oral cancer patient. An 82-year-old woman was referred to Tokyo Dental College Chiba Hospital with a mass lesion on the tongue. A biopsy revealed a well-differentiated squamous cell carcinoma. Surgical treatment was performed for the tongue carcinoma and tracheotomy for management of the airway. On postoperative day 5, the patient exhibited loss of consciousness (Glasgow Coma Scale: E1, VT, M1; Japan Coma Scale: III-300). The patient's vital signs were all normal, as were the results of a full blood count, brain-CT, MRI, and MRA. Only the arm dropping test was positive. Therefore, the cause of the coma was diagnosed as conversion disorder. Seven hours later, the patient showed a complete recovery.

7.
Bull Tokyo Dent Coll ; 57(2): 91-6, 2016.
Article in English | MEDLINE | ID: mdl-27320298

ABSTRACT

Here we report a case of Kussmaul's disease, or sialodochitis fibrinosa. This rare disease is characterized by recurrent swelling of the salivary glands, which then discharge clots of fibrin into the oral cavity. An 80-year-old man with a history of allergic rhinitis visited our department with the chief complaint of pain in the bilateral parotid gland area on eating. An initial examination revealed mild swelling and tenderness in this region, and indurations could be felt around the bilateral parotid papillae. Pressure on the parotid glands induced discharge of gelatinous plugs from the parotid papillae. No pus was discharged, and there were no palpable hard objects. Panoramic X-ray showed no obvious focus of dental infection, and there was no calcification in the parotid gland region. Magnetic resonance imaging revealed segmental dilatation of the main ducts of both parotid ducts, with no signs of displacement due to sialoliths or tumors, or of abnormal saliva leakage. Two courses of antibiotic therapy resulted in no improvement. During treatment, gelatinous plugs (fibrin clots) obstructing the left parotid duct were dislodged by massage, which prevented further blockage by encouraging salivary outflow. The obstruction persisted in the right parotid duct, however. Therefore, the distal portion of the right parotid duct was partially resected and the opening into the mouth enlarged, which, in combination with massage, prevented further obstruction. The pain and swelling of the parotid gland and discharge of gelatinous plugs improved, with no further recurrence at 12 months postoperatively. This case is presented along with a review of the relevant literature.


Subject(s)
Parotid Diseases/diagnosis , Parotid Diseases/pathology , Parotid Diseases/therapy , Parotid Gland/pathology , Salivary Ducts/pathology , Salivary Ducts/surgery , Aged, 80 and over , Diagnosis, Differential , Dilatation, Pathologic/pathology , Fibrin/metabolism , Humans , Magnetic Resonance Imaging , Male , Massage , Parotid Diseases/physiopathology , Radiography, Panoramic , Tomography, X-Ray Computed
8.
Bull Tokyo Dent Coll ; 56(1): 49-55, 2015.
Article in English | MEDLINE | ID: mdl-25765575

ABSTRACT

Cystadenoma, a common benign tumor derived from glandular tissue, generally occurs in the appendix, ovaries, kidney, or pancreas. While rare in the oral and maxillofacial region, they do sometimes occur in the parotid or minor salivary glands. We report a case of cystadenoma arising in the upper lip region. The patient was a 37-year-old woman referred to our hospital with a painless mass on the left upper lip initially found during treatment at a local dental clinic. The medical history was non-contributory. The 7×5-mm mass was well-defined, elastic, and flexible. The surface of the mucosa appeared healthy. The mass was clinically diagnosed as a benign tumor of the left upper lip. Because the tumor was painless and slow-growing, and magnetic resonance imaging suggested that it was benign, resection was performed under local anesthesia without biopsy. Histopathologically, cystadenoma was diagnosed. No signs of recurrence or metastasis have been seen as of 24 months postoperatively and the progress of the patient has been satisfactory.


Subject(s)
Cystadenoma/pathology , Lip , Mouth Neoplasms/pathology , Adult , Cystadenoma/surgery , Female , Humans , Mouth Neoplasms/surgery
9.
Bull Tokyo Dent Coll ; 54(4): 259-64, 2013.
Article in English | MEDLINE | ID: mdl-24521552

ABSTRACT

The Frequency with which impacted supernumerary teeth are encountered in a clinical setting is relatively high, with the majority of such cases occurrig in the median maxillary region, and very few in the molar region. In the molar region, mandibular distomolars (fourth molars) are very rare. Although a small number of case reports have described impacted supernumerary distomolars, very few have compared third molars and distomolars. Herein, the authors report two cases involving mandibular distomolars and one case a maxillary distomolar. In each of these cases, the third molar and distomolar were extracted and a macroscopic morphological analysis conducted. The results were then compared with those of the latest available literature.


Subject(s)
Molar/abnormalities , Tooth, Supernumerary/diagnosis , Adult , Female , Humans , Molar, Third/abnormalities , Tooth Crown/abnormalities , Tooth Root/abnormalities , Tooth, Impacted/diagnosis , Young Adult
10.
Oncol Rep ; 45(2): 448-458, 2021 02.
Article in English | MEDLINE | ID: mdl-33416122

ABSTRACT

Heat shock protein 90 (HSP90) expression is upregulated in numerous types of cancer. However, its role as a candidate for molecular targeted therapy in oral squamous cell carcinoma (OSCC) cells is poorly understood. In the present study, a common upstream search was performed using molecular network analysis software for proteins with expression abnormalities that were found in a proteomic analysis of six OSCC cell lines. HSP90 was identified as a target protein. In clinical samples, high frequencies of HSP90­high expression were detected via immunohistochemistry (26/58; 45%). Furthermore, the HSP90 expression status was associated with cervical lymph node metastasis (P=0.015). Furthermore, the potential of HSP90 as a candidate for molecular targeted therapy in OSCC cells was investigated using the HSP90 inhibitors 17­dimethylaminoethylamino­17­demethoxygeldanamycin (17­DMAG) and ganetespib. KON cells, which strongly express HSP90, were treated with the HSP90 inhibitors. The numbers of living cells in the 17­DMAG and ganetespib­treated groups were lower than those in the non­treated group. The cells treated with the inhibitors demonstrated reduced cell viability and migration, and this was associated with markedly decreased levels of the HSP90 target proteins EGFR, phospho­EGFR, phospho­MEK and phospho­MAPK in the treated groups compared with the non­treated group. To the best of our knowledge, this was the first study to investigate the effects of 17­DMAG and ganetespib on OSCC cells. The present results indicated the potential of HSP90 as a useful candidate for molecular targeted therapy in OSCC. However, additional studies with larger sample sizes are required to confirm these findings.


Subject(s)
Benzoquinones/pharmacology , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Lactams, Macrocyclic/pharmacology , Mouth Neoplasms/therapy , Squamous Cell Carcinoma of Head and Neck/therapy , Triazoles/pharmacology , Adult , Aged , Aged, 80 and over , Animals , Benzoquinones/therapeutic use , Cell Line, Tumor , Cell Proliferation/drug effects , Chemotherapy, Adjuvant/methods , Drug Screening Assays, Antitumor , Female , HSP90 Heat-Shock Proteins/metabolism , Humans , Lactams, Macrocyclic/therapeutic use , Male , Middle Aged , Molecular Targeted Therapy/methods , Mouth Mucosa/pathology , Mouth Mucosa/surgery , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Prognosis , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Survival Rate , Triazoles/therapeutic use
11.
Case Rep Dent ; 2021: 5542570, 2021.
Article in English | MEDLINE | ID: mdl-34336305

ABSTRACT

AIM: There are several techniques for the treatment of mandibular condylar fractures. This is the first report of the high submandibular anteroparotid approach for open reduction and internal fixation of condylar fracture. MATERIALS AND METHODS: A 41-year-old woman fell indoors and injured her face. She was referred to our department for detailed examination and treatment of a suspected mandibular fracture. X-ray and computed tomography showed a right mandibular condylar base fracture and lateral dislocation of the fracture fragment. Open reduction and internal fixation procedures were performed for a right mandibular condylar fracture under general anesthesia. The mandibular ramus was reached by approaching from the inferior margin of the mandible, delaminating the masseter fascia posteriorly, and bypassing the anterior margin of the parotid gland. Once the fractured bone was reached, reduction and fixation were performed. RESULTS: We have achieved good results by the high submandibular anteroparotid approach, which is minimally invasive and simple, to reduce and fix condylar fractures. With this approach, no facial artery or retromandibular vein was encountered, and the mental stress for the surgeon was minimal. Postoperative wound infection, parotid gland complications such as parotitis and salivary fistula, facial nerve dysfunction such as facial paralysis, and esthetic disorders such as scarring were not observed. CONCLUSIONS: Although it is necessary to examine more cases in the future, the high submandibular anteroparotid approach may be useful as a new approach for open reduction and internal fixation of condylar fractures.

12.
Anticancer Res ; 41(5): 2297-2306, 2021 May.
Article in English | MEDLINE | ID: mdl-33952455

ABSTRACT

BACKGROUND/AIM: Phosphodiesterase 5 (PDE5) holds clinical relevance in several pathological states, including lung, breast, and prostate cancer. In this study, we examined PDE5 expression in oral squamous cell carcinoma (OSCC)-derived cell lines and tissues, and the anti-tumour effect of PDE5 inhibitor, sildenafil citrate (SC). MATERIALS AND METHODS: Cell proliferation, cell invasion, and gap closure assays were performed in six OSCC-derived cell lines upon treatment with varying concentrations of SC. PDE5 expression was determined in primary OSCC tissues by western blotting and immunohistochemistry. RESULTS: Elevated PDE5 expression was observed in all cell lines. A concentration-dependent decrease in cell viability, invasion rate, and migration was observed after SC treatment. A significant correlation (p=0.05) was observed between elevated PDE5 expression and lymphatic infiltration in OSCC tissues. CONCLUSION: PDE5 plays an important role in carcinogenesis of OSCC, and the specific inhibition of PDE5 may be an effective chemotherapeutic strategy.


Subject(s)
Carcinoma, Squamous Cell/enzymology , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Mouth Neoplasms/enzymology , Sildenafil Citrate/pharmacology , Blotting, Western , Carcinoma, Squamous Cell/pathology , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Immunohistochemistry , Mouth Neoplasms/pathology , Phosphodiesterase 5 Inhibitors/pharmacology
13.
Cancer Manag Res ; 12: 1069-1078, 2020.
Article in English | MEDLINE | ID: mdl-32104087

ABSTRACT

PURPOSE: Hangeshashinto (TJ-14), a Kampo medicine comprising seven types of herbs, has been used in Japan to alleviate the side effects associated with anticancer drug treatments. However, the pharmacological effects of this medicine currently remain unclear. The present study aimed to demonstrate the efficacy of TJ-14 against anticancer drug-induced stomatitis, the pain associated with which may have a negative impact on mastication and swallowing. METHODS: Mucositis was induced in Sprague-Dawley rats by cancer chemotherapy. Changes in body weight, stomatitis grades, histopathological scores, and oral bacterial counts were examined among TJ-14-treated, saline-treated, and Control (no treatment) rats. In vitro studies, including cell proliferation and wound healing assays, using epidermal keratinocyte and fibroblast cell lines were conducted. RESULTS: The local application of TJ-14 exerted strong antibacterial effects and attenuated oral chemotherapy-induced stomatitis in rats. TJ-14 also increased the viability and invasion of epidermal keratinocytes and fibroblasts. CONCLUSION: The present results demonstrated the potential of TJ-14 to attenuate chemotherapy-induced stomatitis.

14.
Case Rep Dent ; 2020: 8851174, 2020.
Article in English | MEDLINE | ID: mdl-33381324

ABSTRACT

A Stafne bone defect from the mandibular anterior to the premolar region is an extremely rare case. A case of a Stafne bone defect extending from the mandibular anterior to the premolar region was presented. Computed tomography (CT) and magnetic resonance imaging (MRI) suggested that salivary gland tissue connected to the sublingual glands was involved in the formation of the cavity. The patient was a 68-year-old man who was examined at our hospital's emergency outpatient department after a traffic accident. He was referred to our department for the treatment of contusions of the lips and oral cavity. A bone defect in the lingual side of the mandible from the right anterior to the right premolar region was incidentally detected on CT. CT showed a rounded cavity in the lingual side of the mandible that had a lingual opening, was monocystic, and had a cortical margin. The margin of the cavity was relatively dull and regular. MRI showed that the tissue filling the cavity in the lingual side of the mandible had similar signal intensity as the sublingual glands and was contiguous with the normal sublingual glands. Based on these findings, the bone defect was diagnosed as a Stafne bone defect filled with salivary gland tissue connected to the sublingual gland tissue.

15.
Biochem Biophys Rep ; 20: 100697, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31692631

ABSTRACT

No effective, reliable treatment for stomatitis associated with cancer therapy has been established. This study focused on the its effectiveness of ozone nano-bubble water (ONBW) for the treatment of chemotherapy-induced stomatitis. Oral mucositis was induced in 14-week-old male Sprague-Dawley rats (N = 21). The animals were randomly divided into 3 groups: 7 without treatment (control); 7 treated with physiological salt solution (saline); and 7 treated with ONBW. Animals were weighed on Days 7, 9, 11, and 16. Stomatitis grade evaluation and bacterial count measurements were performed before rinsing in all animals 3, 5, and 10 days after acetic acid irritation (Days 9, 11, and 17 respectively). Weight loss after stomatitis creation was observed in all groups, with significant differences between the control and ONBW groups and between the saline and ONBW groups on Day 16. The stomatitis grade did not worsen during the experimental period in any group, with the lowest grades in the ONBW group on Days 11 and 16. Significant differences were identified between the control and ONBW groups and between the saline and ONBW groups on Days 11 and 16. Oral bacterial counts tended to decrease over time in all three groups, with the greatest decrease in the ONBW group, followed by the saline group. The decrease in the bacterial count was steepest in the ONBW group. Rinsing out the oral cavity with ONBW decreased bacterial counts and encouraged the healing of oral chemotherapy-induced stomatitis. ONBW may be an effective treatment for chemotherapy-induced stomatitis.

17.
3D Print Med ; 4(1): 6, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30148203

ABSTRACT

BACKGROUND: In the oral and maxillofacial surgery and dentistry fields, the use of three-dimensional (3D) patient-specific organ models is increasing, which has increased the cost of obtaining them. We developed an environment in our facility in which we can design, fabricate, and use 3D models called the "One-stop 3D printing lab". The lab made it possible to quickly and inexpensively produce the 3D models that are indispensable for oral and maxillofacial surgery. We report our 3D model fabrication environment after determining the dimensional accuracy of the models with different laminating pitches (; layer thickness) after fabricating over 300 3D models. Considerations were made for further reducing modeling cost and model print time. MDCT imaging was performed using a dry human mandible, and 3D CAD data were generated from the DICOM image data. 3D models were fabricated with a fused deposition modeling (FDM) 3D printer MF-2000 (MUTOH) with a laminating pitch of 0.2 mm, 0.3 mm, 0.4 mm, or 0.5 mm. Each 3D model was then subjected to reverse scanning to evaluate the modeling conditions and deformation during modeling. For the 3D image processing system, Volume Extractor 3.0 (i-Plants Systems) and POLYGONALmeister V2 (UEL) were used. For the comparative evaluation of CAD data, spGauge 2014.1 (Armonicos) was used. RESULTS: As the laminating pitch increased, the weight of the 3D model, model print time, and material cost decreased, and no significant reduction in geometric accuracy was observed. CONCLUSIONS: The amount of modeling material used and preparation cost were reduced by increasing the laminating pitch. The "One-stop 3D printing lab" made it possible to produce 3D models daily. The use of 3D models in the oral and maxillofacial surgery and dentistry fields will likely increase, and we expect that low-cost FDM 3D printers that can produce low-cost 3D models will play a significant role.

18.
Stem Cell Res Ther ; 9(1): 12, 2018 01 22.
Article in English | MEDLINE | ID: mdl-29357927

ABSTRACT

BACKGROUND: Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. METHODS: Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. RESULTS: Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. CONCLUSIONS: Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.


Subject(s)
Bone Regeneration/physiology , Cleidocranial Dysplasia/therapy , Core Binding Factor Alpha 1 Subunit/genetics , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/transplantation , Osteoblasts/cytology , Osteogenesis/physiology , Osteoporosis/therapy , Animals , CRISPR-Cas Systems/genetics , Cell Differentiation , Cells, Cultured , Cleidocranial Dysplasia/genetics , Codon, Nonsense/genetics , Disease Models, Animal , Humans , Kruppel-Like Factor 4 , Osteoporosis/pathology , Rats
20.
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