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Sample records for embryonic craniofacial mesenchymal

  1. The suture provides a niche for mesenchymal stem cells of craniofacial bones

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    Zhao, Hu; Feng, Jifan; Ho, Thach-Vu; Grimes, Weston; Urata, Mark; Chai, Yang

    2015-01-01

    Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the major MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating these cells are an indispensible stem cell population. Twist1+/− mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair. PMID:25799059

  2. Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research

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    Satoru Morikawa

    2016-01-01

    Full Text Available Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs. The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research.

  3. Molecular fingerprinting of TGFbeta-treated embryonic maxillary mesenchymal cells.

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    Pisano, M M; Mukhopadhyay, P; Greene, R M

    2003-11-01

    The transforming growth factor-beta (TGF(beta)) family represents a class of signaling molecules that plays a central role in normal embryonic development, specifically in development of the craniofacial region. Members of this family are vital to development of the secondary palate where they regulate maxillary and palate mesenchymal cell proliferation and extracellular matrix synthesis. The function of this growth factor family is particularly critical in that perturbation of either process results in a cleft of the palate. While the cellular and phenotypic effects of TGF(beta) on embryonic craniofacial tissue have been extensively cataloged, the specific genes that function as downstream mediators of TGF(beta) in maxillary/palatal development are poorly defined. Gene expression arrays offer the ability to conduct a rapid, simultaneous assessment of hundreds to thousands of differentially expressed genes in a single study. Inasmuch as the downstream sequelae of TGF(beta) action are only partially defined, a complementary DNA (cDNA) expression array technology (Clontech's Atlas Mouse cDNA Expression Arrays), was utilized to delineate a profile of differentially expressed genes from TGF(beta)-treated primary cultures of murine embryonic maxillary mesenchymal cells. Hybridization of a membrane-based cDNA array (1178 genes) was performed with 32P-labeled cDNA probes synthesized from RNA isolated from either TGF(beta)-treated or vehicle-treated embryonic maxillary mesenchymal cells. Resultant phosphorimages were subject to AtlasImage analysis in order to determine differences in gene expression between control and TGF(beta)-treated maxillary mesenchymal cells. Of the 1178 arrayed genes, 552 (47%) demonstrated detectable levels of expression. Steady state levels of 22 genes were up-regulated, while those of 8 other genes were down-regulated, by a factor of twofold or greater in response to TGF(beta). Affected genes could be grouped into three general functional

  4. Advances of mesenchymal stem cells derived from bone marrow and dental tissue in craniofacial tissue engineering.

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    Yang, Maobin; Zhang, Hongming; Gangolli, Riddhi

    2014-05-01

    Bone and dental tissues in craniofacial region work as an important aesthetic and functional unit. Reconstruction of craniofacial tissue defects is highly expected to ensure patients to maintain good quality of life. Tissue engineering and regenerative medicine have been developed in the last two decades, and been advanced with the stem cell technology. Bone marrow derived mesenchymal stem cells are one of the most extensively studied post-natal stem cell population, and are widely utilized in cell-based therapy. Dental tissue derived mesenchymal stem cells are a relatively new stem cell population that isolated from various dental tissues. These cells can undergo multilineage differentiation including osteogenic and odontogenic differentiation, thus provide an alternative source of mesenchymal stem cells for tissue engineering. In this review, we discuss the important issues in mesenchymal stem cell biology including the origin and functions of mesenchymal stem cells, compare the properties of these two types of mesenchymal cells, update recent basic research and clinic applications in this field, and address important future challenges.

  5. [Expression of embryonic markers in pterygium derived mesenchymal cells].

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    Pascual, G; Montes, M A; Pérez-Rico, C; Pérez-Kohler, B; Bellón, J M; Buján, J

    2010-12-01

    Destruction of the limbal epithelium barrier is the most important mechanism of pterygium formation (conjunctiva proliferation, encroaching onto the cornea). It is thought to arise from activated and proliferating limbal epithelial stem cells. The objective of this study is to evaluate the presence of undifferentiated mesenchymal cells (stem cells) in cultured cells extracted from human pterygium. Cells from 6 human pterygium were isolated by explantation and placed in cultures with amniomax medium. Once the monolayer was reached the cells were seeded onto 24 well microplates. The cells were studied in the second sub-culture. The immunohistochemical expression of different embryonic stem cell markers, OCT3/4 and CD9, was analysed. The differentiated phenotypes were characterised with the monoclonal antibodies anti-CD31, α-actin and vimentin. All the cell populations obtained from pterygium showed vimentin expression. Less than 1% of the cells were positive for CD31 and α-actin markers. The majority of the cell population was positive for OCT3/4 and CD9. The cell population obtained from pterygium expressed mesenchymal cell phenotype and embryonic markers, such us OCT3/4 and CD9. This undifferentiated population could be involved in the large recurrence rate of this type of tissue after surgery. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Micro-computed tomography-based phenotypic approaches in embryology: procedural artifacts on assessments of embryonic craniofacial growth and development

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    Logan C Cairine

    2010-02-01

    Full Text Available Abstract Background Growing demand for three dimensional (3D digital images of embryos for purposes of phenotypic assessment drives implementation of new histological and imaging techniques. Among these micro-computed tomography (μCT has recently been utilized as an effective and practical method for generating images at resolutions permitting 3D quantitative analysis of gross morphological attributes of developing tissues and organs in embryonic mice. However, histological processing in preparation for μCT scanning induces changes in organ size and shape. Establishing normative expectations for experimentally induced changes in size and shape will be an important feature of 3D μCT-based phenotypic assessments, especially if quantifying differences in the values of those parameters between comparison sets of developing embryos is a primary aim. Toward that end, we assessed the nature and degree of morphological artifacts attending μCT scanning following use of common fixatives, using a two dimensional (2D landmark geometric morphometric approach to track the accumulation of distortions affecting the embryonic head from the native, uterine state through to fixation and subsequent scanning. Results Bouin's fixation reduced average centroid sizes of embryonic mouse crania by approximately 30% and substantially altered the morphometric shape, as measured by the shift in Procrustes distance, from the unfixed state, after the data were normalized for naturally occurring shape variation. Subsequent μCT scanning produced negligible changes in size but did appear to reduce or even reverse fixation-induced random shape changes. Mixtures of paraformaldehyde + glutaraldehyde reduced average centroid sizes by 2-3%. Changes in craniofacial shape progressively increased post-fixation. Conclusions The degree to which artifacts are introduced in the generation of random craniofacial shape variation relates to the degree of specimen dehydration during the

  7. Micro-computed tomography-based phenotypic approaches in embryology: procedural artifacts on assessments of embryonic craniofacial growth and development.

    Science.gov (United States)

    Schmidt, Eric J; Parsons, Trish E; Jamniczky, Heather A; Gitelman, Julian; Trpkov, Cvett; Boughner, Julia C; Logan, C Cairine; Sensen, Christoph W; Hallgrímsson, Benedikt

    2010-02-17

    Growing demand for three dimensional (3D) digital images of embryos for purposes of phenotypic assessment drives implementation of new histological and imaging techniques. Among these micro-computed tomography (microCT) has recently been utilized as an effective and practical method for generating images at resolutions permitting 3D quantitative analysis of gross morphological attributes of developing tissues and organs in embryonic mice. However, histological processing in preparation for microCT scanning induces changes in organ size and shape. Establishing normative expectations for experimentally induced changes in size and shape will be an important feature of 3D microCT-based phenotypic assessments, especially if quantifying differences in the values of those parameters between comparison sets of developing embryos is a primary aim. Toward that end, we assessed the nature and degree of morphological artifacts attending microCT scanning following use of common fixatives, using a two dimensional (2D) landmark geometric morphometric approach to track the accumulation of distortions affecting the embryonic head from the native, uterine state through to fixation and subsequent scanning. Bouin's fixation reduced average centroid sizes of embryonic mouse crania by approximately 30% and substantially altered the morphometric shape, as measured by the shift in Procrustes distance, from the unfixed state, after the data were normalized for naturally occurring shape variation. Subsequent microCT scanning produced negligible changes in size but did appear to reduce or even reverse fixation-induced random shape changes. Mixtures of paraformaldehyde + glutaraldehyde reduced average centroid sizes by 2-3%. Changes in craniofacial shape progressively increased post-fixation. The degree to which artifacts are introduced in the generation of random craniofacial shape variation relates to the degree of specimen dehydration during the initial fixation. Fixation methods that

  8. Improving PEEK bioactivity for craniofacial reconstruction using a 3D printed scaffold embedded with mesenchymal stem cells.

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    Roskies, Michael; Jordan, Jack O; Fang, Dongdong; Abdallah, Mohamed-Nur; Hier, Michael P; Mlynarek, Alex; Tamimi, Faleh; Tran, Simon D

    2016-07-01

    Polyetheretherketone (PEEK) is a bioinert thermoplastic that has been investigated for its potential use in craniofacial reconstruction; however, its use in clinical practice is limited by a poor integration with adjacent bone upon implantation. To improve the bone-implant interface, two strategies have been employed: to modify its surface or to impregnate PEEK with bioactive materials. This study attempts to combine and improve upon the two approaches by modifying the internal structure into a trabecular network and to impregnate PEEK with mesenchymal stem cells. Furthermore, we compare the newly designed PEEK scaffolds' interactions with both bone-derived (BMSC) and adipose (ADSC) stem cells. Customized PEEK scaffolds were designed to incorporate a trabecular microstructure using a computer-aided design program and then printed via selective laser sintering (SLS), a 3D-printing process with exceptional accuracy. The scaffold structure was evaluated using microCT. Scanning electron microscopy (SEM) was used to evaluate scaffold morphology with and without mesenchymal stem cells (MSCs). Adipose and bone marrow mesenchymal cells were isolated from rats and cultured on scaffolds. Cell proliferation and differentiation were assessed using alamarBlue and alkaline phosphatase assays, respectively. Cell morphology after one week of co-culturing cells with PEEK scaffolds was evaluated using SEM. SLS 3D printing fabricated scaffolds with a porosity of 36.38% ± 6.66 and density of 1.309 g/cm(2). Cell morphology resembled viable fibroblasts attaching to the surface and micropores of the scaffold. PEEK scaffolds maintained the viability of both ADSCs and BMSCs; however, ADSCs demonstrated higher osteodifferentiation than BMSCs (p PEEK scaffolds that maintain the viability of adipose and bone marrow-derived MSCs and induce the osteodifferentiation of the adipose-derived MSCs. The combination of 3D printed PEEK scaffolds with MSCs could overcome some of the limitations

  9. The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction

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    Jin, Yong-Ri; Turcotte, Taryn J.; Crocker, Alison L.; Han, Xiang Hua; Yoon, Jeong Kyo

    2011-01-01

    R-spondins are a recently characterized family of secreted proteins that activate Wnt/β-catenin signaling. Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice. Mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate. We found that loss of the mouse Rspo2 gene significantly disrupted Wnt/β-catenin signaling and gene expression within the first branchial arch (BA1). Rspo2, which is normally expressed in BA1 mesenchymal cells, regulates gene expression through a unique ectoderm-mesenchyme interaction loop. The Rspo2 protein, potentially in combination with ectoderm-derived Wnt ligands, up-regulates Msx1 and Msx2 expression within mesenchymal cells. In contrast, Rspo2 regulates expression of the Dlx5, Dlx6, and Hand2 genes in mesenchymal cells via inducing expression of their upstream activator, Endothelin1 (Edn1), within ectodermal cells. Loss of Rspo2 also causes increased cell apoptosis, especially within the aboral (or caudal) domain of the BA1, resulting in hypoplasia of the BA1. Severely reduced expression of Fgf8, a survival factor for mesenchymal cells, in the ectoderm of Rspo2−/− embryos is likely responsible for increased cell apoptosis. Additionally, we found that cleft palate in Rspo2−/− mice is not associated with defects intrinsic to the palatal shelves. A possible cause of cleft palate is a delay of proper palatal shelf elevation that may result from the small mandible and a failure of lowering the tongue. Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate. PMID:21237142

  10. Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes.

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    Christophe M Raynaud

    Full Text Available Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs derived in vitro from human embryonic stem cells (hESCs. Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

  11. Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells

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    Romain Barbet; Isabelle Peiffer; Antoinette Hatzfeld; Pierre Charbord; Jacques A. Hatzfeld

    2011-01-01

    We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs ...

  12. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

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    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  13. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

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    Varga, Nóra; Veréb, Zoltán; Rajnavölgyi, Éva; Német, Katalin; Uher, Ferenc; Sarkadi, Balázs; Apáti, Ágota

    2011-01-01

    Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  14. Undifferentiated (embryonal) liver sarcoma: synchronous and metachronous occurrence with neoplasms other than mesenchymal liver hamartoma.

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    Gasljevic, Gorana; Lamovec, Janez; Jancar, Janez

    2011-08-01

    Undifferentiated (embryonal) liver sarcoma (UELS) is a rare tumor that typically occurs in children. The association of UELS with neoplasm other than mesenchymal liver hamartoma is exceedingly rare. The aim of the study was to report 3 cases of UELS, 2 of them being interesting because of their association with another neoplasm, vaginal embryonal rhabdomyosarcoma in a teenage girl and B-acute lymphoblastic leukemia in a middle-aged woman. Besides, one of our cases of UELS, in a 58-year-old woman, is an extremely rare presentation of such a tumor in a middle-aged adult. The patient's clinical features, therapy, and pathologic results were reviewed; immunohistochemical analysis and, in 2 cases, electron microscopy were performed. In this study, all 3 patients were females aged 13, 13, and 58 years. Histopathologic evaluation of resected liver tumors confirmed the diagnosis of UELS in all of them. In 2 of the cases, metachronous occurrence of UELS with vaginal embryonal rhabdomyosarcoma in a teenage girl and B-acute lymphoblastic leukemia in a middle-aged woman is described. Careful clinical analysis, histologic studies, and immunohistochemistry are mandatory to distinguish UELS from other hepatic malignancies with similar or overlapping features and to exclude the possibility of other tumors that may be considered in the differential diagnosis. The association of UELS with another neoplasm is exceedingly rare. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Derivation of Stromal (Skeletal, Mesenchymal) Stem-like cells from Human Embryonic Stem Cells

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    Mahmood, Amer; Harkness, Linda; Abdallah, Basem

    2012-01-01

    EBs using BMP2 (bone morphogenic protein 2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold......Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESC) is a pre-requisite for their use in clinical applications. However, there is no standard protocol for differentiating hESC into osteoblastic cells. The aim of this study was to identify the emergence of a human...... stromal (mesenchymal, skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESC in a feeder-free environment using serum replacement and as suspension aggregates (embryoid...

  16. Mesenchymal and embryonic characteristics of stem cells obtained from mouse dental pulp.

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    Guimarães, Elisalva Teixeira; Cruz, Gabriela Silva; de Jesus, Alan Araújo; Lacerda de Carvalho, Acácia Fernandes; Rogatto, Silvia Regina; Pereira, Lygia da Veiga; Ribeiro-dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    2011-11-01

    Several studies have demonstrated that human dental pulp is a source of mesenchymal stem cells. To better understand the biological properties of these cells we isolated and characterized stem cells from the dental pulp of EGFP transgenic mice. The pulp tissue was gently separated from the roots of teeth extracted from C57BL/6 mice, and cultured under appropriate conditions. Flow cytometry, RT-PCR, light microscopy (staining for alkaline phosphatase) and immunofluorescence were used to investigate the expression of stem cell markers. The presence of chromosomal abnormalities was evaluated by G banding. The mouse dental pulp stem cells (mDPSC) were highly proliferative, plastic-adherent, and exhibited a polymorphic morphology predominantly with stellate or fusiform shapes. The presence of cell clusters was observed in cultures of mDPSC. Some cells were positive for alkaline phosphatase. The karyotype was normal until the 5th passage. The Pou5f1/Oct-4 and ZFP42/Rex-1, but not Nanog transcripts were detected in mDPSC. Flow cytometry and fluorescence analyses revealed the presence of a heterogeneous population positive for embryonic and mesenchymal cell markers. Adipogenic, chondrogenic and osteogenic differentiation was achieved after two weeks of cell culture under chemically defined in vitro conditions. In addition, some elongated cells spontaneously acquired a contraction capacity. Our results reinforce that the dental pulp is an important source of adult stem cells and encourage studies on therapeutic potential of mDPSC in experimental disease models. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Inhibition of IKK/NF-κB Signaling Enhances Differentiation of Mesenchymal Stromal Cells from Human Embryonic Stem Cells.

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    Deng, Peng; Zhou, Chenchen; Alvarez, Ruth; Hong, Christine; Wang, Cun-Yu

    2016-04-12

    Embryonic stem cell-derived mesenchymal stromal cells (MSCs; also known as mesenchymal stem cells) represent a promising source for bone regenerative medicine. Despite remarkable advances in stem cell biology, the molecular mechanism regulating differentiation of human embryonic stem cells (hESCs) into MSCs remains poorly understood. Here, we report that inhibition of IκB kinase (IKK)/nuclear factor kappa B (NF-κB) signaling enhances differentiation of hESCs into MSCs by expediting the loss of pluripotent markers and increasing the expression of MSC surface markers. In addition, a significantly higher quantity of MSCs was produced from hESCs with IKK/NF-κB suppression. These isolated MSCs displayed evident multipotency with capacity to terminally differentiate into osteoblasts, chondrocytes, and adipocytes in vitro and to form bone in vivo. Collectively, our data provide important insights into the role of NF-κB in mesenchymal lineage specification during hESC differentiation, suggesting that IKK inhibitors could be utilized as an adjuvant in generating MSCs for cell-mediated therapies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Regulation of proliferation of embryonic heart mesenchyme: Role of transforming growth factor-beta 1 and the interstitial matrix

    International Nuclear Information System (INIS)

    Choy, M.; Armstrong, M.T.; Armstrong, P.B.

    1990-01-01

    Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage

  19. Fluorescence-Activated Cell Sorting of EGFP-Labeled Neural Crest Cells From Murine Embryonic Craniofacial Tissue

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    Saurabh Singh

    2005-01-01

    Full Text Available During the early stages of embryogenesis, pluripotent neural crest cells (NCC are known to migrate from the neural folds to populate multiple target sites in the embryo where they differentiate into various derivatives, including cartilage, bone, connective tissue, melanocytes, glia, and neurons of the peripheral nervous system. The ability to obtain pure NCC populations is essential to enable molecular analyses of neural crest induction, migration, and/or differentiation. Crossing Wnt1-Cre and Z/EG transgenic mouse lines resulted in offspring in which the Wnt1-Cre transgene activated permanent EGFP expression only in NCC. The present report demonstrates a flow cytometric method to sort and isolate populations of EGFP-labeled NCC. The identity of the sorted neural crest cells was confirmed by assaying expression of known marker genes by TaqMan Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR. The molecular strategy described in this report provides a means to extract intact RNA from a pure population of NCC thus enabling analysis of gene expression in a defined population of embryonic precursor cells critical to development.

  20. Derivation of Stromal (Skeletal and Mesenchymal) Stem-Like Cells from Human Embryonic Stem Cells

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    Harkness, Linda; Abdallah, Basem M.; Elsafadi, Mona; Al-Nbaheen, May S.; Aldahmash, Abdullah; Kassem, Moustapha

    2012-01-01

    Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESCs) is a prerequisite for their use in clinical applications. However, there is no standard protocol for differentiating hESCs into osteoblastic cells. The aim of this study was to identify the emergence of a human stromal (mesenchymal and skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESCs in a feeder-free environment using serum replacement and as suspension aggregates (embryoid bodies; hEBs). Over a 20 day developmental period, the hEBs demonstrated increasing enrichment for cells expressing hMSC markers: CD29, CD44, CD63, CD56, CD71, CD73, CD105, CD106, and CD166 as revealed by immunohistochemical staining and flow cytometry (fluorescence-activated cell sorting) analysis. Ex vivo differentiation of hEBs using bone morphogenic protein 2 (BMP2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold, revealed bone and cartilage, and fibrous tissue elements after 8 weeks. These tissues were of human origin and there was no evidence of differentiation to nonmesodermal tissues. hEBs implanted in the absence of HA/TCP formed vacuolated tissue containing glandular, fibrous and muscle-like tissue elements. Conversely, implantation of undifferentiated hESCs resulted in the formation of a teratoma containing a mixture of endodermal, mesodermal, and ectodermal tissues. Our study demonstrates that hMSC-like cells can be obtained from hESCs and they can be induced to form skeletal tissues in vivo when combined with HA/TCP. These findings are relevant for tissue engineering and suggest that differentiated hEBs can provide an unlimited source for

  1. Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

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    Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

    2016-08-01

    During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells.

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    Barbet, Romain; Peiffer, Isabelle; Hatzfeld, Antoinette; Charbord, Pierre; Hatzfeld, Jacques A

    2011-01-01

    We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs (hES-MSCs), and hMSCs. Analysis of differentiation genes indicated that hES-MSCs express the sarcomeric muscle lineage in addition to the classical mesenchymal lineages, suggesting they are more primitive than hMSCs. Transcript analysis of membrane antigens suggests that IL1R1(low), BMPR1B(low), FLT4(low), LRRC32(low), and CD34 may be good candidates for the detection and isolation of the most primitive hMSCs. The expression in hMSCs of cytokine genes, such as IL6, IL8, or FLT3LG, without expression of the corresponding receptor, suggests a role for these cytokines in the paracrine control of stem cell niches. Our database may be shared with other laboratories in order to explore the considerable clinical potential of hES-MSCs, which appear to represent an intermediate developmental stage between hESCs and hMSCs.

  3. Differential bone-forming capacity of osteogenic cells from either embryonic stem cells or bone marrow-derived mesenchymal stem cells

    NARCIS (Netherlands)

    Both, Sanne Karijn; van Apeldoorn, Aart A.; Jukes, J.M.; Englund, Mikael C.O.; Hyllner, Johan; van Blitterswijk, Clemens; de Boer, Jan

    2011-01-01

    For more than a decade, human mesenchymal stem cells (hMSCs) have been used in bone tissue-engineering research. More recently some of the focus in this field has shifted towards the use of embryonic stem cells. While it is well known that hMSCs are able to form bone when implanted subcutaneously in

  4. Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages.

    Science.gov (United States)

    Jiao, Fei; Wang, Juan; Dong, Zhao-Lun; Wu, Min-Juan; Zhao, Ting-Bao; Li, Dan-Dan; Wang, Xin

    2012-08-01

    Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them "human limb bud-derived mesenchymal stem cells" (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro.

  5. Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a newly identified cause of congenital ear malformation

    Directory of Open Access Journals (Sweden)

    Lely A. Quina

    2012-11-01

    Hmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural-crest-derived craniofacial mesenchyme (CM, whereas Hmx1 is expressed normally in retinal progenitors, sensory ganglia and in CM, which is derived from mesoderm. High-throughput resequencing of 1 Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ∼410 kb immediately downstream of the Hmx1 transcription unit. Further sequence analysis of this region reveals a 5777-bp deletion located ∼80 kb downstream in dmbo/dmbo rats that is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ∼500 bp, which is a candidate distal enhancer and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural-crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear

  6. S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland.

    Directory of Open Access Journals (Sweden)

    Kotaro Horiguchi

    Full Text Available The anterior and intermediate lobes of the pituitary gland develop through invagination of the oral ectoderm and as they are endocrine tissues, they participate in the maintenance of vital functions via the synthesis and secretion of numerous hormones. We recently observed that several extrapituitary cells invade the anterior lobe of the developing pituitary gland. This raised the question of the origin(s of these S100β-positive cells, which are not classic endocrine cells but instead comprise a heterogeneous cell population with plural roles, especially as stem/progenitor cells. To better understand the roles of these S100β-positive cells, we performed immunohistochemical analysis using several markers in S100β/GFP-TG rats, which express GFP in S100β-expressing cells under control of the S100β promoter. GFP-positive cells were present as mesenchymal cells surrounding the developing pituitary gland and at Atwell's recess but were not present in the anterior lobe on embryonic day 15.5. These cells were negative for SOX2, a pituitary stem/progenitor marker, and PRRX1, a mesenchyme and pituitary stem/progenitor marker. However, three days later, GFP-positive and PRRX1-positive (but SOX2-negative cells were observed in the parenchyma of the anterior lobe. Furthermore, some GFP-positive cells were positive for vimentin, p75, isolectin B4, DESMIN, and Ki67. These data suggest that S100β-positive cells of extrapituitary origin invade the anterior lobe, undergoing proliferation and diverse transformation during pituitary organogenesis.

  7. S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland.

    Science.gov (United States)

    Horiguchi, Kotaro; Yako, Hideji; Yoshida, Saishu; Fujiwara, Ken; Tsukada, Takehiro; Kanno, Naoko; Ueharu, Hiroki; Nishihara, Hiroto; Kato, Takako; Yashiro, Takashi; Kato, Yukio

    2016-01-01

    The anterior and intermediate lobes of the pituitary gland develop through invagination of the oral ectoderm and as they are endocrine tissues, they participate in the maintenance of vital functions via the synthesis and secretion of numerous hormones. We recently observed that several extrapituitary cells invade the anterior lobe of the developing pituitary gland. This raised the question of the origin(s) of these S100β-positive cells, which are not classic endocrine cells but instead comprise a heterogeneous cell population with plural roles, especially as stem/progenitor cells. To better understand the roles of these S100β-positive cells, we performed immunohistochemical analysis using several markers in S100β/GFP-TG rats, which express GFP in S100β-expressing cells under control of the S100β promoter. GFP-positive cells were present as mesenchymal cells surrounding the developing pituitary gland and at Atwell's recess but were not present in the anterior lobe on embryonic day 15.5. These cells were negative for SOX2, a pituitary stem/progenitor marker, and PRRX1, a mesenchyme and pituitary stem/progenitor marker. However, three days later, GFP-positive and PRRX1-positive (but SOX2-negative) cells were observed in the parenchyma of the anterior lobe. Furthermore, some GFP-positive cells were positive for vimentin, p75, isolectin B4, DESMIN, and Ki67. These data suggest that S100β-positive cells of extrapituitary origin invade the anterior lobe, undergoing proliferation and diverse transformation during pituitary organogenesis.

  8. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix.

    Science.gov (United States)

    Wang, Yafei; Yu, Dongsheng; Liu, Zhiming; Zhou, Fang; Dai, Jun; Wu, Bingbing; Zhou, Jing; Heng, Boon Chin; Zou, Xiao Hui; Ouyang, Hongwei; Liu, Hua

    2017-08-14

    Mesenchymal stem cell therapy for osteoarthritis (OA) has been widely investigated, but the mechanisms are still unclear. Exosomes that serve as carriers of genetic information have been implicated in many diseases and are known to participate in many physiological processes. Here, we investigate the therapeutic potential of exosomes from human embryonic stem cell-induced mesenchymal stem cells (ESC-MSCs) in alleviating osteoarthritis (OA). Exosomes were harvested from conditioned culture media of ESC-MSCs by a sequential centrifugation process. Primary mouse chondrocytes treated with interleukin 1 beta (IL-1β) were used as an in vitro model to evaluate the effects of the conditioned medium with or without exosomes and titrated doses of isolated exosomes for 48 hours, prior to immunocytochemistry or western blot analysis. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of C57BL/6 J mice as an OA model. This was followed by intra-articular injection of either ESC-MSCs or their exosomes. Cartilage destruction and matrix degradation were evaluated with histological staining and OARSI scores at the post-surgery 8 weeks. We found that intra-articular injection of ESC-MSCs alleviated cartilage destruction and matrix degradation in the DMM model. Further in vitro studies illustrated that this effect was exerted through ESC-MSC-derived exosomes. These exosomes maintained the chondrocyte phenotype by increasing collagen type II synthesis and decreasing ADAMTS5 expression in the presence of IL-1β. Immunocytochemistry revealed colocalization of the exosomes and collagen type II-positive chondrocytes. Subsequent intra-articular injection of exosomes derived from ESC-MSCs successfully impeded cartilage destruction in the DMM model. The exosomes from ESC-MSCs exert a beneficial therapeutic effect on OA by balancing the synthesis and degradation of chondrocyte extracellular matrix (ECM), which in turn provides a new target for OA drug

  9. Fuz regulates craniofacial development through tissue specific responses to signaling factors.

    Directory of Open Access Journals (Sweden)

    Zichao Zhang

    Full Text Available The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/- mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/- mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/- mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.

  10. Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-beta/Activin/Nodal signaling using SB-431542

    DEFF Research Database (Denmark)

    Mahmood, Amer; Harkness, Linda; Schrøder, Henrik Daa

    2010-01-01

    Directing differentiation of human embryonic stem cells (hESC) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESC in regenerative medicine procedures. Here, we report a protocol for directing the differentiation of hESC into mesenchymal...... in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSC): CD44(+) (100%), CD73(+) (98%), CD146(+) (96%) and CD166(+) (88%) with the ability...... progenitor cells. We demonstrate that inhibition of TGF-beta/Activin/Nodal signaling during embryoid bodies (EB) formation using SB-431542 (SB) in serum free medium, markedly up-regulated paraxial mesodermal markers (TBX6, TBX5), and several myogenic developmental markers including early myogenic...

  11. Chorionic villi derived mesenchymal like stem cells and expression of embryonic stem cells markers during long-term culturing.

    Science.gov (United States)

    Katsiani, E; Garas, A; Skentou, C; Tsezou, A; Messini, C I; Dafopoulos, K; Daponte, A; Messinis, I E

    2016-09-01

    Mesenchymal stem cells (MSCs) can be obtained from a variety of human tissues. MSCs derived from placental chorionic villi of the first trimester are likely to resemble, biologically, embryonic stem cells (ESC), due to the earlier development stage of placenta. In the present study long-term cultures of MSC-like cells were assessed in order to evaluate MSCs multipotent characteristics and molecular features during the period of culture. CV-cells obtained from 10 samples of chorionic villus displayed typical fibroblastoid morphology, undergone 20 passages during a period of 120 days, maintaining a stable karyotype throughout long term expansion. The cells were positive, for CD90, CD73, CD105, CD29, CD44, HLA ABC antigens and negative for CD14, CD34, AC133, and HLA DR antigens as resulted from the flow cytometry analysis. CV-cells were differentiated in adipocytes, osteoblasts, chondrocytes and neuronal cells under specific culture conditions. The expression of the ESC-gene markers POU5F1 (Oct-4) and NANOG was observed at earliest stages (4-12 passages) and not at the late stages (14-20 passages) by RT-PCR analysis. ZFP42 and SOX2 expression were not detected. Moreover, CV-cells were found to express GATA4 but not NES (Nestin). Chorionic villi-derived cells possess multipotent properties, display high proliferation rate and self-renew capacity, share common surface antigens with adult MSCs and express certain embryonics stem cells gene markers. These characteristics highlight chorionic villi as an attractive source of MSCs for the needs of regenerative medicine.

  12. Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage.

    Science.gov (United States)

    Wang, Xiaofang; Lazorchak, Adam S; Song, Li; Li, Enqin; Zhang, Zhenwu; Jiang, Bin; Xu, Ren-He

    2016-02-01

    Mesenchymal stem/stromal cells (MSCs) have great clinical potential in modulating inflammation and promoting tissue repair. Human embryonic stem cells (hESCs) have recently emerged as a potentially superior cell source for MSCs. However, the generation methods reported so far vary greatly in quality and efficiency. Here, we describe a novel method to rapidly and efficiently produce MSCs from hESCs via a trophoblast-like intermediate stage in approximately 11-16 days. We term these cells "T-MSCs" and show that T-MSCs express a phenotype and differentiation potential minimally required to define MSCs. T-MSCs exhibit potent immunomodulatory activity in vitro as they can remarkably inhibit proliferation of cocultured T and B lymphocytes. Unlike bone marrow MSCs, T-MSCs do not have increased expression of inflammatory mediators in response to IFNγ. Moreover, T-MSCs constitutively express a high level of the immune inhibitory ligand PD-L1 and elicit strong and durable efficacy in two distinct animal models of autoimmune disease, dextran sulfate sodium induced colitis, and experimental autoimmune encephalomyelitis, at doses near those approved for clinical trials. Together, we present a simple and fast derivation method to generate MSCs from hESCs, which possess potent immunomodulatory properties in vitro and in vivo and may serve as a novel and ideal candidate for MSC-based therapies. © 2015 AlphaMed Press.

  13. Msx homeobox gene family and craniofacial development.

    Science.gov (United States)

    Alappat, Sylvia; Zhang, Zun Yi; Chen, Yi Ping

    2003-12-01

    Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the phenotypic abnormalities shown in knockout mice and in humans. This review summarizes studies on the expression, regulation, and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice. Key words: Msx genes, craniofacial, tooth, cleft palate, suture, development, transcription factor, signaling molecule.

  14. Controlled surface topography regulates collective 3D migration by epithelial-mesenchymal composite embryonic tissues.

    Science.gov (United States)

    Song, Jiho; Shawky, Joseph H; Kim, YongTae; Hazar, Melis; LeDuc, Philip R; Sitti, Metin; Davidson, Lance A

    2015-07-01

    Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. N-acetylcysteine-pretreated human embryonic mesenchymal stem cell administration protects against bleomycin-induced lung injury.

    Science.gov (United States)

    Wang, Qiao; Zhu, Hong; Zhou, Wu-Gang; Guo, Xiao-Can; Wu, Min-Juan; Xu, Zhen-Yu; Jiang, Jun-feng; Shen, Ce; Liu, Hou-Qi

    2013-08-01

    The transplantation of mesenchymal stem cells (MSCs) has been reported to be a promising approach in the treatment of acute lung injury. However, the poor efficacy of transplanted MSCs is one of the serious handicaps in the progress of MSC-based therapy. Therefore, the purpose of this study was to investigate whether the pretreatment of human embryonic MSCs (hMSCs) with an antioxidant, namely N-acetylcysteine (NAC), can improve the efficacy of hMSC transplantation in lung injury. In vitro, the antioxidant capacity of NAC-pretreated hMSCs was assessed using intracellular reactive oxygen species (ROS) and glutathione assays and cell adhesion and spreading assays. In vivo, the therapeutic potential of NAC-pretreated hMSCs was assessed in a bleomycin-induced model of lung injury in nude mice. The pretreatment of hMSCs with NAC improved antioxidant capacity to defend against redox imbalances through the elimination of cellular ROS, increasing cellular glutathione levels, and the enhancement of cell adhesion and spreading when exposed to oxidative stresses in vitro. In addition, the administration of NAC-pretreated hMSCs to nude mice with bleomycin-induced lung injury decreased the pathological grade of lung inflammation and fibrosis, hydroxyproline content and numbers of neutrophils and inflammatory cytokines in bronchoalveolar lavage fluid and apoptotic cells, while enhancing the retention and proliferation of hMSCs in injured lung tissue and improving the survival rate of mice compared with results from untreated hMSCs. The pretreatment of hMSCs with NAC could be a promising therapeutic approach to improving cell transplantation and, therefore, the treatment of lung injury.

  16. [Proliferative capacity of mesenchymal stem cells from human fetal bone marrow and their ability to differentiate into the derivative cell types of three embryonic germ layers].

    Science.gov (United States)

    Wang, Yue-Chun; Zhang, Yuan

    2008-06-25

    Strong proliferative capacity and the ability to differentiate into the derivative cell types of three embryonic germ layers are the two important characteristics of embryonic stem cells. To study whether the mesenchymal stem cells from human fetal bone marrow (hfBM-MSCs) possess these embryonic stem cell-like biological characteristics, hfBM-MSCs were isolated from bone barrows and further purified according to the different adherence of different kinds of cells to the wall of culture flask. The cell cycle of hfBM-MSCs and MSC-specific surface markers such as CD29, CD44, etc were identified using flow cytometry. The expressions of human telomerase reverse transcriptase (hTERT), the embryonic stem cell-specific antigens, such as Oct4 and SSEA-4 were detected with immunocytochemistry at the protein level and were also tested by RT-PCR at the mRNA level. Then, hfBM-MSCs were induced to differentiate toward neuron cells, adipose cells, and islet B cells under certain conditions. It was found that 92.3% passage-4 hfBM-MSCs and 96.1% passage-5 hfBM-MSCs were at G(0)/G(1) phase respectively. hfBM-MSCs expressed CD44, CD106 and adhesion molecule CD29, but not antigens of hematopoietic cells CD34 and CD45, and almost not antigens related to graft-versus-host disease (GVHD), such as HLA-DR, CD40 and CD80. hfBM-MSCs expressed the embryonic stem cell-specific antigens such as Oct4, SSEA-4, and also hTERT. Exposure of these cells to various inductive agents resulted in morphological changes towards neuron-like cells, adipose-like cells, and islet B-like cells and they were tested to be positive for related characteristic markers. These results suggest that there are plenty of MSCs in human fetal bone marrow, and hfBM-MSCs possess the embryonic stem cell-like biological characteristics, moreover, they have a lower immunogenic nature. Thus, hfBM-MSCs provide an ideal source for tissue engineering and cellular therapeutics.

  17. Embryonic Stem Cell-Derived Mesenchymal Stem Cells (MSCs) Have a Superior Neuroprotective Capacity Over Fetal MSCs in the Hypoxic-Ischemic Mouse Brain.

    Science.gov (United States)

    Hawkins, Kate E; Corcelli, Michelangelo; Dowding, Kate; Ranzoni, Anna M; Vlahova, Filipa; Hau, Kwan-Leong; Hunjan, Avina; Peebles, Donald; Gressens, Pierre; Hagberg, Henrik; de Coppi, Paolo; Hristova, Mariya; Guillot, Pascale V

    2018-05-01

    Human mesenchymal stem cells (MSCs) have huge potential for regenerative medicine. In particular, the use of pluripotent stem cell-derived mesenchymal stem cells (PSC-MSCs) overcomes the hurdle of replicative senescence associated with the in vitro expansion of primary cells and has increased therapeutic benefits in comparison to the use of various adult sources of MSCs in a wide range of animal disease models. On the other hand, fetal MSCs exhibit faster growth kinetics and possess longer telomeres and a wider differentiation potential than adult MSCs. Here, for the first time, we compare the therapeutic potential of PSC-MSCs (ES-MSCs from embryonic stem cells) to fetal MSCs (AF-MSCs from the amniotic fluid), demonstrating that ES-MSCs have a superior neuroprotective potential over AF-MSCs in the mouse brain following hypoxia-ischemia. Further, we demonstrate that nuclear factor (NF)-κB-stimulated interleukin (IL)-13 production contributes to an increased in vitro anti-inflammatory potential of ES-MSC-conditioned medium (CM) over AF-MSC-CM, thus suggesting a potential mechanism for this observation. Moreover, we show that induced pluripotent stem cell-derived MSCs (iMSCs) exhibit many similarities to ES-MSCs, including enhanced NF-κB signaling and IL-13 production in comparison to AF-MSCs. Future studies should assess whether iMSCs also exhibit similar neuroprotective potential to ES-MSCs, thus presenting a potential strategy to overcome the ethical issues associated with the use of embryonic stem cells and providing a potential source of cells for autologous use against neonatal hypoxic-ischemic encephalopathy in humans. Stem Cells Translational Medicine 2018;7:439-449. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  18. Isolation and characterization of true mesenchymal stem cells derived from human term decidua capable of multilineage differentiation into all 3 embryonic layers.

    Science.gov (United States)

    Macias, Maria I; Grande, Jesús; Moreno, Ana; Domínguez, Irene; Bornstein, Rafael; Flores, Ana I

    2010-11-01

    The objective of the study was to isolate and characterize a population of mesenchymal stem cells (MSCs) from human term placental membranes. We isolated an adherent cell population from extraembryonic membranes. Morphology, phenotype, growth characteristics, karyotype, and immunological and differentiation properties were analyzed. The isolated placental MSCs were from maternal origin and named as decidua-derived mesenchymal stem cells (DMSCs). DMSCs differentiated into derivatives of all germ layers. It is the first report about placental MSC differentiation into alveolar type II cells. Clonally expanded DMSCs differentiated into all embryonic layers, including pulmonary cells. DMSCs showed higher life span than placental cells from fetal origin and proliferated without genomic instability. The data suggest that DMSCs are true multipotent MSCs, distinguishing them from other placental MSCs. DMSCs could be safely used in the mother as a potential source of MSCs for pelvic floor dysfunctions and immunological diseases. Additionally, frozen DMSCs can be stored for both autologous and allogeneic tissue regeneration. Copyright © 2010 Mosby, Inc. All rights reserved.

  19. Utilization of human amniotic mesenchymal cells as feeder layers to sustain propagation of human embryonic stem cells in the undifferentiated state.

    Science.gov (United States)

    Zhang, Kehua; Cai, Zhe; Li, Yang; Shu, Jun; Pan, Lin; Wan, Fang; Li, Hong; Huang, Xiaojie; He, Chun; Liu, Yanqiu; Cui, Xiaohui; Xu, Yang; Gao, Yan; Wu, Liqun; Cao, Shanxia; Li, Lingsong

    2011-08-01

    Human embryonic stem (ES) cells are usually maintained in the undifferentiated state by culturing on feeder cells layers of mouse embryonic fibroblasts (MEFs). However, MEFs are not suitable to support human ES cells used for clinical purpose because of risk of zoonosis from animal cells. Therefore, human tissue-based feeder layers need to be developed for human ES cells for clinical purpose. Hereof we report that human amniotic mesenchymal cells (hAMCs) could act as feeder cells for human ES cells, because they are easily obtained and relatively exempt from ethical problem. Like MEFs, hAMCs could act as feeder cells for human ES cells to grow well on. The self-renewal rate of human ES cells cultured on hAMCs feeders was higher than that on MEFs and human amniotic epithelial cells determined by measurement of colonial diameters and growth curve as well as cell cycle analysis. Both immunofluorescence staining and immunoblotting showed that human ES cells cultured on hAMCs expressed stem cell markers such as Oct-3/4, Sox2, and NANOG. Verified by embryoid body formation in vitro and teratoma formation in vivo, we found out that after 20 passages of culture, human ES cells grown on hAMCs feeders could still retain the potency of differentiating into three germ layers. Taken together, our data suggested hAMCs may be safe feeder cells to sustain the propagation of human ES cells in undifferentiated state for future therapeutic use.

  20. Isolation and characterization of exosome from human embryonic stem cell-derived c-myc-immortalized mesenchymal stem cells

    NARCIS (Netherlands)

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Padmanabhan, Jayanthi; Choo, Andre; De Kleijn, Dominique P V; Lim, Sai Kiang

    2016-01-01

    Mesenchymal stem cells (MSC) are currently the cell type of choice in many cell therapy trials. The number of therapeutic applications for MSCs registered as product IND submissions with the FDA and initiation of registered clinical trials has increased substantially in recent years, in particular

  1. Neuroembryology and functional anatomy of craniofacial clefts

    OpenAIRE

    Ewings, Ember L.; Carstens, Michael H.

    2009-01-01

    The master plan of all vertebrate embryos is based on neuroanatomy. The embryo can be anatomically divided into discrete units called neuromeres so that each carries unique genetic traits. Embryonic neural crest cells arising from each neuromere induce development of nerves and concomitant arteries and support the development of specific craniofacial tissues or developmental fields. Fields are assembled upon each other in a programmed spatiotemporal order. Abnormalities in one field can affec...

  2. Complementarity of SOMAscan to LC-MS/MS and RNA-seq for quantitative profiling of human embryonic and mesenchymal stem cells.

    Science.gov (United States)

    Billing, Anja M; Ben Hamidane, Hisham; Bhagwat, Aditya M; Cotton, Richard J; Dib, Shaima S; Kumar, Pankaj; Hayat, Shahina; Goswami, Neha; Suhre, Karsten; Rafii, Arash; Graumann, Johannes

    2017-01-06

    Dynamic range limitations are challenging to proteomics, particularly in clinical samples. Affinity proteomics partially overcomes this, yet suffers from dependence on reagent quality. SOMAscan, an aptamer-based platform for over 1000 proteins, avoids that issue using nucleic acid binders. Targets include low expressed proteins not easily accessible by other approaches. Here we report on the potential of SOMAscan for the study of differently sourced mesenchymal stem cells (MSC) in comparison to LC-MS/MS and RNA sequencing. While targeting fewer analytes, SOMAscan displays high precision and dynamic range coverage, allowing quantification of proteins not measured by the other platforms. Expression between cell types (ESC and MSC) was compared across techniques and uncovered the expected large differences. Sourcing was investigated by comparing subtypes: bone marrow-derived, standard in clinical studies, and ESC-derived MSC, thought to hold similar potential but devoid of inter-donor variability and proliferating faster in vitro. We confirmed subtype-equivalency, as well as vesicle and extracellular matrix related processes in MSC. In contrast, the proliferative nature of ESC was captured less by SOMAscan, where nuclear proteins are underrepresented. The complementary of SOMAscan allowed the comprehensive exploration of CD markers and signaling molecules, not readily accessible otherwise and offering unprecedented potential in subtype characterization. Mesenchymal stem cells (MSC) represent promising stem cell-derived therapeutics as indicated by their application in >500 clinical trials currently registered with the NIH. Tissue-derived MSC require invasive harvesting and imply donor-to-donor differences, to which embryonic stem cell (ESC)-derived MSC may provide an alternative and thus warrant thorough characterization. In continuation of our previous study where we compared in depth embryonic stem cells (ESC) and MSC from two sources (bone marrow and ESC

  3. Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3.

    Science.gov (United States)

    Kapacee, Zoher; Yeung, Ching-Yan Chloé; Lu, Yinhui; Crabtree, David; Holmes, David F; Kadler, Karl E

    2010-10-01

    Tendon-like tissue generated from stem cells in vitro has the potential to replace tendons and ligaments lost through injury and disease. However, thus far, no information has been available on the mechanism of tendon formation in vitro and how to accelerate the process. We show here that human mesenchymal stem cells (MSCs) and bone marrow-derived mononuclear cells (BM-MNCs) can generate tendon-like tissue in 7days mediated by transforming growth factor (TGF) β3. MSCs cultured in fixed-length fibrin gels spontaneously synthesized narrow-diameter collagen fibrils and exhibited fibripositors (actin-rich, collagen fibril-containing plasma membrane protrusions) identical to those that occur in embryonic tendon. In contrast, BM-MNCs did not synthesize tendon-like tissue under these conditions. We performed real-time PCR analysis of MSCs and BM-MNCs. MSCs upregulated genes encoding type I collagen, TGFβ3, and Smad2 at the time of maximum contraction of the tendon-like tissue (7days). Western blot analysis showed phosphorylation of Smad2 at maximum contraction. The TGFβ inhibitor SB-431542, blocked the phosphorylation of Smad2 and stopped the formation of tendon-like tissue. Quantitative PCR showed that BM-MNCs expressed very low levels of TGFβ3 compared to MSCs. Therefore we added exogenous TGFβ3 protein to BM-MNCs in fibrin gels, which resulted in phosphorylation of Smad2, synthesis of collagen fibrils, the appearance of fibripositors at the plasma membrane, and the formation of tendon-like tissue. In conclusion, MSCs that self-generate TGFβ signaling or the addition of TGFβ3 protein to BM-MNCs in fixed-length fibrin gels spontaneously make embryonic tendon-like tissue in vitro within 7days. Copyright © 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  4. Demonstration of β-adrenergic receptors and catecholamine-mediated effects on cell proliferation in embryonic palatal tissue

    International Nuclear Information System (INIS)

    Pisano, M.M.

    1986-01-01

    The ability of catecholamines to modulate cell proliferation, differentiation and morphogenesis in other systems, and modulate adenylate cyclase activity in the developing palate during the period of cellular differentiation, made it of interest to determine their involvement in palatal ontogenesis. Catecholamines exert their physiologic effects via interaction with distinct membrane-bound receptors, one class being the B-adrenergic receptors which are coupled to stimulation of adenylate cyclase and the generation of cAMP. A direct radioligand binding technique utilizing the B-adrenergic antagonist [ 3 H]-dihydroalprenolol ([ 3 H]-DHA) was employed in the identification of B-adrenergic receptors in the developing murine secondary palate. Specific binding of [ 3 H]-DHA in embryonic (day 13) palatal tissue homogenates was saturable and of high affinity. The functionality of B-adrenergic receptor binding sites was assessed from the ability of embryonic palate mesenchmyal cells in vitro to respond to catecholamines with elevations of cAMP. Embryonic palate mesenchymal cells responded to various B-adrenergic catecholamine agonists with significant, dose-dependent accumulations of intracellular cAMP. Embryonic (day 13) maxillary tissue homogenates were analyzed for the presence of catecholamines by high performance liquid chromatography and radioenzymatic assay. Since normal palatal and craniofacial morphogenesis depends on proper temporal and spatial patterns of growth, the effect of B-adrenergic catecholamines on embryonic palate mesenchymal cell proliferation was investigated

  5. Altered growth, differentiation, and responsiveness to epidermal growth factor of human embryonic mesenchymal cells of palate by persistent rubella virus infection

    International Nuclear Information System (INIS)

    Yoneda, T.; Urade, M.; Sakuda, M.; Miyazaki, T.

    1986-01-01

    We previously demonstrated that human embryonic mesenchymal cells derived from the palate (HEMP cells) retain alkaline phosphatase (ALP) content and capacity for collagen synthesis after long-term culture, and their growth is markedly stimulated by epidermal growth factor (EGF). There was a dramatic decrease in ALP content and capacity to synthesize collagen in HEMP cells (HEMP-RV cells) persistently infected with rubella virus (RV). EGF increased ALP activity and decreased collagen synthesis in HEMP cells, whereas EGF showed no effect on these activities in HEMP-RV cells. Growth of HEMP-RV cells was slightly reduced compared with that of HEMP cells. EGF stimulated growth of HEMP cells and to a lesser extent of HEMP-RV cells. Binding of 125 I-EGF to cell-surface receptors in HEMP-RV cells was, to our surprise, twice as much as that in HEMP cells. However, internalization of bound 125 I-EGF in HEMP-RV cells was profoundly diminished. Thus, persistent RV infection causes not only changes in HEMP cell growth and differentiation but a decrease in or loss of HEMP cell responsiveness to EGF. The effects of persistent RV infection on palatal cell differentiation as well as growth may be responsible for the pathogenesis of congenital rubella. Furthermore, since HEMP cells appear to be closely related to osteoblasts, these results suggest a mechanism for RV-induced osseous abnormalities manifested in congenital rubella patients

  6. Secretome of Aggregated Embryonic Stem Cell-Derived Mesenchymal Stem Cell Modulates the Release of Inflammatory Factors in Lipopolysaccharide-Induced Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Mohammadi Ghahhari, Nastaran; Maghsood, Faezeh; Jahandideh, Saeed; Lotfinia, Majid; Lak, Shirin; Johari, Behrooz; Azarnezhad, Asaad; Kadivar, Mehdi

    2018-07-01

    Bone marrow mesenchymal stem cells (BM-MSCs) have emerged as a potential therapy for various inflammatory diseases. Because of some limitations, several recent studies have suggested the use of embryonic stem cell-derived MSCs (ESC-MSCs) as an alternative for BM-MSCs. Some of the therapeutic effects of the ESC-MSCs are related to the secretion of a broad array of cytokines and growth factors, known as secretome. Harnessing this secretome for therapeutic applications requires the optimization of production of secretary molecules. It has been shown that aggregation of MSCs into 3D spheroids, as a preconditioning strategy, can enhance immunomodulatory potential of such cells. In this study, we investigated the effect of secretome derived from human ESC-MSCs (hESC-MSCs) spheroids on secretion of IL-1β, IL-10, and tumor necrosis factor α (TNF-α) from lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMCs). In the present study, after immunophenotyping and considering mesodermal differentiation of hESC-MSCs, the cells were non-adherently grown to prepare 3D aggregates, and then conditioned medium or secretome was extracted from the cultures. Afterwards, the anti-inflammatory effects of the secretome were assessed in an in vitro model of inflammation. Results from this study showed that aggregate-prepared secretome from hESC-MSCs was able to significantly decrease the secretion of TNF-α (301.7 ± 5.906, p strategy to increase immunomodulatory characteristics of hESC-MSCs.

  7. Craniofacial Surgery Fellowship Websites.

    Science.gov (United States)

    Silvestre, Jason; Agarwal, Divyansh; Taylor, Jesse A

    2016-06-01

    Applicants for craniofacial surgery fellowships utilize Internet-based resources like the San Francisco (SF) Match to manage applications. The purpose of this study was to evaluate the accessibility and content of craniofacial surgery fellowship websites (CSFWs). A list of available craniofacial surgery fellowships was compiled from directories of the American Society of Craniofacial Surgery (ACSFS) and SF Match. Accessibility of CSFWs was assessed via links from these directories and a Google search. Craniofacial surgery fellowship websites were evaluated on education and recruitment content and compared via program characteristics. Twenty-four of the 28 US-based craniofacial surgery fellowship programs had a CSFW (86%). The ACSFS and SF Match databases had limited CSFW accessibility, but a Google search revealed most CSFWs had the top search result (76%). In total, CSFWs provided an average of 39% of education and recruitment variables. While most programs provided fellowship program descriptions (96%), application links (96%), and faculty listings (83%), relatively few provided rotation schedules (13%), fellow selection process information (13%), or interview dates (8%). CSFW content did not vary by program location, faculty size, accreditation status, or institutional affiliations (P > 0.05). Craniofacial surgery fellowships often lack readily accessible websites from national program lists and have limited information for interested applicants. The consistent lack of online information across programs suggests future opportunities exist to improve these educational resources.

  8. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Arianne van Koppen

    Full Text Available Chronic kidney disease (CKD is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance and effective renal plasma flow (PAH clearance were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.

  9. Isolation and Characterization of Exosome from Human Embryonic Stem Cell-Derived C-Myc-Immortalized Mesenchymal Stem Cells.

    Science.gov (United States)

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Padmanabhan, Jayanthi; Choo, Andre; de Kleijn, Dominique P V; Lim, Sai Kiang

    2016-01-01

    Mesenchymal stem cells (MSC) are currently the cell type of choice in many cell therapy trials. The number of therapeutic applications for MSCs registered as product IND submissions with the FDA and initiation of registered clinical trials has increased substantially in recent years, in particular between 2006 and 2012. However, defined mechanisms of action underpinning the therapeutic efficacy of MSCs are lacking, but they are increasingly attributed to MSC trophic secretion rather than their differentiation potential. A promising secreted therapeutic candidate is an extracellular vesicle (EV) known as the exosome. The use of exosomes instead of cells as a therapeutic agent provides several advantages. A critical advantage is the prospect of a conventional pharmaceutical manufacturing process that is highly scalable and amenable to the stringent manufacturing process. For example, MSCs used as producers of therapeutics, and not as therapeutics per se, could be immortalized to generate infinitely expansible clonal lines to enhance the reproducible production of therapeutic exosomes. In this chapter, we will describe the immortalization of MSCs, and the production, isolation, and characterization of exosomes from immortalized MSC.

  10. Imaging of human glioblastoma cells and their interactions with mesenchymal stem cells in the zebrafish (Danio rerio) embryonic brain

    International Nuclear Information System (INIS)

    Vittori, Milos; Breznik, Barbara; Gredar, Tajda; Hrovat, Katja; Bizjak Mali, Lilijana; Lah, Tamara T

    2016-01-01

    An attractive approach in the study of human cancers is the use of transparent zebrafish (Danio rerio) embryos, which enable the visualization of cancer progression in a living animal. We implanted mixtures of fluorescently labeled glioblastoma (GBM) cells and bonemarrow-derived mesenchymal stem cells (MSCs) into zebrafish embryos to study the cellular pathways of their invasion and the interactions between these cells in vivo. By developing and applying a carbocyanine-dye-compatible clearing protocol for observation of cells in deep tissues, we showed that U87 and U373 GBM cells rapidly aggregated into tumor masses in the ventricles and midbrain hemispheres of the zebrafish embryo brain, and invaded the central nervous system, often using the ventricular system and the central canal of the spinal cord. However, the GBM cells did not leave the central nervous system. With co-injection of differentially labeled cultured GBM cells and MSCs, the implanted cells formed mixed tumor masses in the brain. We observed tight associations between GBM cells and MSCs, and possible cell-fusion events. GBM cells and MSCs used similar invasion routes in the central nervous system. This simple model can be used to study the molecular pathways of cellular processes in GBM cell invasion, and their interactions with various types of stromal cells in double or triple cell co-cultures, to design anti-GBM cell therapies that use MSCs as vectors

  11. Chondrogenesis of Embryonic Stem Cell-Derived Mesenchymal Stem Cells Induced by TGFβ1 and BMP7 Through Increased TGFβ Receptor Expression and Endogenous TGFβ1 Production.

    Science.gov (United States)

    Lee, Patrick T; Li, Wan-Ju

    2017-01-01

    For decades stem cells have proven to be invaluable to the study of tissue development. More recently, mesenchymal stem cells (MSCs) derived from embryonic stem cells (ESCs) (ESC-MSCs) have emerged as a cell source with great potential for the future of biomedical research due to their enhanced proliferative capability compared to adult tissue-derived MSCs and effectiveness of musculoskeletal lineage-specific cell differentiation compared to ESCs. We have previously compared the properties and differentiation potential of ESC-MSCs to bone marrow-derived MSCs. In this study, we evaluated the potential of TGFβ1 and BMP7 to induce chondrogenic differentiation of ESC-MSCs compared to that of TGFβ1 alone and further investigated the cellular phenotype and intracellular signaling in response to these induction conditions. Our results showed that the expression of cartilage-associated markers in ESC-MSCs induced by the TGFβ1 and BMP7 combination was increased compared to induction with TGFβ1 alone. The TGFβ1 and BMP7 combination upregulated the expression of TGFβ receptor and the production of endogenous TGFβs compared to TGFβ1 induction. The growth factor combination also increasingly activated both of the TGF and BMP signaling pathways, and inhibition of the signaling pathways led to reduced chondrogenesis of ESC-MSCs. Our findings suggest that by adding BMP7 to TGFβ1-supplemented induction medium, ESC-MSC chondrogenesis is upregulated through increased production of endogenous TGFβ and activities of TGFβ and BMP signaling. J. Cell. Biochem. 118: 172-181, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

    Science.gov (United States)

    Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei

    2013-01-01

    Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models. PMID:22788986

  13. Neural Crest-Derived Mesenchymal Cells Require Wnt Signaling for Their Development and Drive Invagination of the Telencephalic Midline

    Science.gov (United States)

    Choe, Youngshik; Zarbalis, Konstantinos S.; Pleasure, Samuel J.

    2014-01-01

    Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs) leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis. PMID:24516524

  14. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

    Directory of Open Access Journals (Sweden)

    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  15. Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye, and axial development.

    Science.gov (United States)

    Foerst-Potts, L; Sadler, T W

    1997-05-01

    In mouse embryos, the muscle segment homeobox genes, Msx-1 and Msx-2 are expressed during critical stages of neural tube, neural crest, and craniofacial development, suggesting that these genes play important roles in organogenesis and cell differentiation. Although the patterns of expression are intriguing, little is known about the function of these genes in vertebrate embryonic development. Therefore, the expression of both genes, separately and together, was disrupted using antisense oligodeoxynucleotides and whole embryo culture techniques. Antisense attenuation of Msx-1 during early stages of neurulation produced hypoplasia of the maxillary, mandibular, and frontonasal prominences, eye anomalies, and somite and neural tube abnormalities. Eye defects consisted of enlarged optic vesicles, which may ultimately result in micropthalmia similar to that observed in Small eye mice homozygous for mutations in the Pax-6 gene. Histological sections and SEM analysis revealed a thinning of the neuroepithelium in the diencephalon and optic vesicle and mesenchymal deficiencies in the craniofacial region. Injections of Msx-2 antisense oligodeoxynucleotides produced similar malformations as those targeting Msx-1, with the exception that there was an increase in number and severity of neural tube and somite defects. Embryos injected with the combination of Msx-1 + Msx-2 antisense oligodeoxynucleotides showed no novel abnormalities, suggesting that the genes do not operate in a redundant manner.

  16. The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats

    Directory of Open Access Journals (Sweden)

    Sang Wook Lee

    2018-01-01

    Full Text Available Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC-derived multipotent mesenchymal stem cells (M-MSCs on ketamine-induced cystitis (KC in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells of M-MSCs (KC+M-MSC group or PBS vehicle (KC group were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells to that of an identical dose of adult bone marrow (BM-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105 of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic

  17. Neuroembryology and functional anatomy of craniofacial clefts

    Directory of Open Access Journals (Sweden)

    Ewings Ember

    2009-10-01

    Full Text Available The master plan of all vertebrate embryos is based on neuroanatomy. The embryo can be anatomically divided into discrete units called neuromeres so that each carries unique genetic traits. Embryonic neural crest cells arising from each neuromere induce development of nerves and concomitant arteries and support the development of specific craniofacial tissues or developmental fields. Fields are assembled upon each other in a programmed spatiotemporal order. Abnormalities in one field can affect the shape and position of developing adjacent fields. Craniofacial clefts represent states of excess or deficiency within and between specific developmental fields. The neuromeric organization of the embryo is the common denominator for understanding normal anatomy and pathology of the head and neck. Tessier′s observational cleft classification system can be redefined using neuroanatomic embryology. Reassessment of Tessier′s empiric observations demonstrates a more rational rearrangement of cleft zones, particularly near the midline. Neuromeric theory is also a means to understand and define other common craniofacial problems. Cleft palate, encephaloceles, craniosynostosis and cranial base defects may be analyzed in the same way.

  18. Six2 Plays an Intrinsic Role in Regulating Proliferation of Mesenchymal Cells in the Developing Palate

    Directory of Open Access Journals (Sweden)

    Dennis O. Okello

    2017-11-01

    Full Text Available Cleft palate is a common congenital abnormality that results from defective secondary palate (SP formation. The Sine oculis-related homeobox 2 (Six2 gene has been linked to abnormalities of craniofacial and kidney development. Our current study examined, for the first time, the specific role of Six2 in embryonic mouse SP development. Six2 mRNA and protein expression were identified in the palatal shelves from embryonic days (E12.5 to E15.5, with peak levels during early stages of palatal shelf outgrowth. Immunohistochemical staining (IHC showed that Six2 protein is abundant throughout the mesenchyme in the oral half of each palatal shelf, whereas there is a pronounced decline in Six2 expression by mesenchyme cells in the nasal half of the palatal shelf by stages E14.5–15.5. An opposite pattern was observed in the surface epithelium of the palatal shelf. Six2 expression was prominent at all stages in the epithelial cell layer located on the nasal side of each palatal shelf but absent from the epithelium located on the oral side of the palatal shelf. Six2 is a putative downstream target of transcription factor Hoxa2 and we previously demonstrated that Hoxa2 plays an intrinsic role in embryonic palate formation. We therefore investigated whether Six2 expression was altered in the developing SP of Hoxa2 null mice. Reverse transcriptase PCR and Western blot analyses revealed that Six2 mRNA and protein levels were upregulated in Hoxa2−/− palatal shelves at stages E12.5–14.5. Moreover, the domain of Six2 protein expression in the palatal mesenchyme of Hoxa2−/− embryos was expanded to include the entire nasal half of the palatal shelf in addition to the oral half. The palatal shelves of Hoxa2−/− embryos displayed a higher density of proliferating, Ki-67 positive palatal mesenchyme cells, as well as a higher density of Six2/Ki-67 double-positive cells. Furthermore, Hoxa2−/− palatal mesenchyme cells in culture displayed both increased

  19. Craniofacial Pain: Brainstem Mechanisms

    Directory of Open Access Journals (Sweden)

    Barry J Sessle

    1996-01-01

    Full Text Available This article reviews recent research advances in animals that have identified critical neural elements in the brainstem receiving and transmitting craniofacial nociceptive inputs, as well as some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. Nociceptive neurones in the trigeminal (V brainstem sensory nuclear complex can be classified as nociceptive-specific (NS or wide dynamic range (WDR. Some of these neurones respond exclusively to sensory inputs evoked by stimulation of facial skin or oral mucosa and have features suggesting that they are critical neural elements involved in the ability to localize an acute superficial pain and sense its intensity and duration. Many of the V brainstem nociceptive neurones, however, receive convergent inputs from afferents supplying deep craniofacial tissues (eg, dural vessel, muscle and skin or mucosa. These neurones are likely involved in deep pain, including headache, because few nociceptive neurones receive inputs exclusively from afferents supplying these tissues. These extensive convergent input patterns also appear to be important factors in pain spread and referral, and in central mechanisms underlying neuroplastic changes in V neuronal properties that may occur with injury and inflammation. For example, application of the small fibre excitant and inflammatory irritant mustard oil into the temporomandibular joint, masseter or tongue musculature induces a prolonged but reversible enhancement of responses to cutaneous and deep afferent inputs of most WDR and NS neurones. These effects may be accompanied by increased electromyographic activity reflexly induced in the masticatory muscles by mustard oil, and involve endogenous N-methyl-D-aspartate and opioid neurochemical mechanisms. Such peripherally induced modulation of brainstem nociceptive neuronal properties reflects the functional plasticity of the central V system, and may be involved in the development of

  20. Dental approach to craniofacial syndromes

    DEFF Research Database (Denmark)

    Kjær, Inger

    2012-01-01

    is essential for insight into craniofacial syndromes. The dentition, thus, becomes central in diagnostics and evaluation of the pathogenesis. Developmental fields can explore and advance the concept of dental approaches to craniofacial syndromes. Discussion. As deviations in teeth persist and do not reorganize...

  1. Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

    Science.gov (United States)

    McElyea, Samantha D; Starbuck, John M; Tumbleson-Brink, Danika M; Harrington, Emily; Blazek, Joshua D; Ghoneima, Ahmed; Kula, Katherine; Roper, Randall J

    2016-11-15

    Trisomy 21 (Ts21) affects craniofacial precursors in individuals with Down syndrome (DS). The resultant craniofacial features in all individuals with Ts21 may significantly affect breathing, eating and speaking. Using mouse models of DS, we have traced the origin of DS-associated craniofacial abnormalities to deficiencies in neural crest cell (NCC) craniofacial precursors early in development. Hypothetically, three copies of Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), a trisomic gene found in most humans with DS and mouse models of DS, may significantly affect craniofacial structure. We hypothesized that we could improve DS-related craniofacial abnormalities in mouse models using a Dyrk1a inhibitor or by normalizing Dyrk1a gene dosage. In vitro and in vivo treatment with Epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, modulated trisomic NCC deficiencies at embryonic time points. Furthermore, prenatal EGCG treatment normalized some craniofacial phenotypes, including cranial vault in adult Ts65Dn mice. Normalization of Dyrk1a copy number in an otherwise trisomic Ts65Dn mice normalized many dimensions of the cranial vault, but did not correct all craniofacial anatomy. These data underscore the complexity of the gene–phenotype relationship in trisomy and suggest that changes in Dyrk1a expression play an important role in morphogenesis and growth of the cranial vault. These results suggest that a temporally specific prenatal therapy may be an effective way to ameliorate some craniofacial anatomical changes associated with DS.

  2. Craniofacial duplication (diprosopus).

    Science.gov (United States)

    Turpin, I M; Furnas, D W; Amlie, R N

    1981-02-01

    No congenital malformation in infants is more profound than anterior craniofacial duplication. The precise term for this rare anomaly is diprosopus, referring to a fetus with a single trunk, normal limbs, and varying degrees of facial duplication. A search of the world literature produced only 16 cases of diprosopus since 1864. Despite the rarity of this anomaly, three such infants were born in the Southern California area during the past year, making this the largest reported series to date. The three infants were born with two distinctly formed faces. Each had four separate eyes, two mouths, two noses, and two ears with a primitive ear or sinus tract at the plane of fusion. In addition, multiple congenital aberrations existed which involved a variety of internal organs. The pathogenesis of diprosopus is not well understood, but environmental stress early in embryologic development has been suggested as a possible factor. The apparent mechanism is a slowing of pregastrulation oxidation with resultant focal developmental arrests.

  3. Development of an embryonic skeletogenic mesenchyme lineage in a sea cucumber reveals the trajectory of change for the evolution of novel structures in echinoderms

    Directory of Open Access Journals (Sweden)

    McCauley Brenna S

    2012-08-01

    Full Text Available Abstract Background The mechanisms by which the conserved genetic “toolkit” for development generates phenotypic disparity across metazoans is poorly understood. Echinoderm larvae provide a great resource for understanding how developmental novelty arises. The sea urchin pluteus larva is dramatically different from basal echinoderm larval types, which include the auricularia-type larva of its sister taxon, the sea cucumbers, and the sea star bipinnaria larva. In particular, the pluteus has a mesodermally-derived larval skeleton that is not present in sea star larvae or any outgroup taxa. To understand the evolutionary origin of this structure, we examined the molecular development of mesoderm in the sea cucumber, Parastichopus parvimensis. Results By comparing gene expression in sea urchins, sea cucumbers and sea stars, we partially reconstructed the mesodermal regulatory state of the echinoderm ancestor. Surprisingly, we also identified expression of the transcription factor alx1 in a cryptic skeletogenic mesenchyme lineage in P. parvimensis. Orthologs of alx1 are expressed exclusively within the sea urchin skeletogenic mesenchyme, but are not expressed in the mesenchyme of the sea star, which suggests that alx1+ mesenchyme is a synapomorphy of at least sea urchins and sea cucumbers. Perturbation of Alx1 demonstrates that this protein is necessary for the formation of the sea cucumber spicule. Overexpression of the sea star alx1 ortholog in sea urchins is sufficient to induce additional skeleton, indicating that the Alx1 protein has not evolved a new function during the evolution of the larval skeleton. Conclusions The proposed echinoderm ancestral mesoderm state is highly conserved between the morphologically similar, but evolutionarily distant, auricularia and bipinnaria larvae. However, the auricularia, but not bipinnaria, also develops a simple skelotogenic cell lineage. Our data indicate that the first step in acquiring these novel

  4. Craniofacial fibrous dysplasia - A review of current management techniques

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    Yadavalli Guruprasad

    2012-01-01

    Full Text Available Fibrous dysplasia is a pathologic condition of bone of unknown etiology with no apparent familial, hereditary or congenital basis. Lichtenstein first coined the term in 1938 and in 1942 he and Jaffe separated it from other fibro-osseous lesions. It is a bone tumor that, although benign, has the potential to cause significant cosmetic and functional disturbance, particularly in the craniofacial skeleton. Its management poses significant challenges to the surgeon. Craniofacial fibrous dysplasia is 1 of 3 types of fibrous dysplasia that can affect the bones of the craniofacial complex, including the mandible and maxilla. Fibrous dysplasia is a skeletal developmental disorder of the bone-forming mesenchyme that manifests as a defect in osteoblastic differentiation and maturation. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. Fibrous dysplasia represents about 2, 5% of all bone tumors and over 7% of all benign tumours. Over the years, we have gained a better understanding of its etiology, clinical behavior, and both surgical and non-surgical treatments.

  5. Craniofacial Reconstruction Evaluation by Geodesic Network

    OpenAIRE

    Zhao, Junli; Liu, Cuiting; Wu, Zhongke; Duan, Fuqing; Wang, Kang; Jia, Taorui; Liu, Quansheng

    2014-01-01

    Craniofacial reconstruction is to estimate an individual’s face model from its skull. It has a widespread application in forensic medicine, archeology, medical cosmetic surgery, and so forth. However, little attention is paid to the evaluation of craniofacial reconstruction. This paper proposes an objective method to evaluate globally and locally the reconstructed craniofacial faces based on the geodesic network. Firstly, the geodesic networks of the reconstructed craniofacial face and the or...

  6. Pediatric considerations in craniofacial trauma.

    Science.gov (United States)

    Koch, Bernadette L

    2014-08-01

    In many respects, craniofacial trauma in children is akin to that in adults. The appearance of fractures and associated injuries is frequently similar. However, the frequencies of different types of fractures and patterns of injury in younger children vary depending on the age of the child. In addition, there are unique aspects that must be considered when imaging the posttraumatic pediatric face. Some of these are based on normal growth and development of the skull base and craniofacial structures, and others on the varying etiologies and mechanisms of craniofacial injury in children, such as injuries related to toppled furniture, nonaccidental trauma, all-terrain vehicle accidents, and impalement injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Craniofacial duplication: a case report.

    Science.gov (United States)

    Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

    2013-09-01

    A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature.

  8. RSK2 is a modulator of craniofacial development.

    Directory of Open Access Journals (Sweden)

    Virginie Laugel-Haushalter

    Full Text Available BACKGROUND: The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized. METHODOLOGY/PRINCIPAL FINDINGS: We examined, using X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, a model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report Rsk mutation produces surpernumerary teeth midline/mesial to the first molar. This highly penetrant phenotype recapitulates more ancestral tooth structures lost with evolution. Most likely this leads to a reduction of the maxillary diastema. Abnormalities of molar shape were generally restricted to the mesial part of both upper and lower first molars (M1. Expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4 was performed at various stages of odontogenesis in wild-type (WT mice. Rsk2 is expressed in the mesenchymal, neural crest-derived compartment, correlating with proliferative areas of the developing teeth. This is consistent with RSK2 functioning in cell cycle control and growth regulation, functions potentially responsible for severe dental phenotypes. To uncover molecular pathways involved in the etiology of these defects, we performed a comparative transcriptomic (DNA microarray analysis of mandibular wild-type versus Rsk2-/Y molars. We further demonstrated a misregulation of several critical genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro. CONCLUSIONS: This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets.

  9. Craniofacial morphology in Muenke syndrome

    DEFF Research Database (Denmark)

    Keller, Mette Kirstine; Hermann, Nuno V; Darvann, Tron A

    2007-01-01

    corresponding to bone was created for each individual. The sutures were inspected for synostosis, and the degree of synostosis was assessed. Increased digital markings were recorded for both groups. Craniofacial morphology was assessed quantitatively using bony landmarks and recording of the midsagittal surface...

  10. Midline Craniofacial Masses in Children

    OpenAIRE

    Van Wyhe, Renae D.; Chamata, Edward S.; Hollier, Larry H.

    2016-01-01

    Nasal dermoids, encephaloceles, and gliomas are rare congenital lesions that result from improper embryologic development. The differentiation between them and a firm understanding of their pathology is necessary to avoid unnecessary complications. In view of their potential intracranial connection, prompt diagnosis and treatment are paramount. The authors review the embryology, diagnoses, radiologic work-up, surgical management, and complications of these midline craniofacial masses in child...

  11. Toward characterization of craniofacial biomechanics.

    Science.gov (United States)

    Szwedowski, Tomasz D; Whyne, Cari M; Fialkov, Jeffrey A

    2010-01-01

    Surgical reconstruction of craniofacial deformities has advanced significantly in recent years. However, unlike orthopedic surgery of the appendicular skeleton, the biomechanical characterization of the human craniofacial skeleton (CFS) has yet to be elucidated. Attempts to simplify facial skeletal structure into straightforward mechanical device analogies have been insufficient in delineating craniofacial biomechanics. Advanced computational engineering analysis methods offer the potential to accurately and completely define the internal mechanical environment of the CFS. This study developed a finite element (FE) model in the I-deas 10 FEM software package of a preserved cadaveric human CFS and compared the predictions of this model against in vitro strain measurement of simulated occlusal loading forces from a single masseter muscle. The FE model applied shell element modeling to capture the behavior of the thin cortical bone that may play an important role in stabilizing the facial structures against functional loads. In vitro testing included strain measurements at 12 locations for a total of 16 independent channels with less than 150 N of tensile force applied through the masseter muscle into the zygomatic arch origin at 4 different orientations, with 3 trials of 500 recorded data points for each loading orientation. Linear regression analysis yielded a moderate prediction (r = 0.57) between the model and experimentally measured strains. Exclusion of strain comparisons in regions that required greater modeling assumptions greatly improved the correlation (r = 0.70). Future validation studies will benefit from improved placement of strain gauges as guided by FE model predicted strain patterns.

  12. Testicular Embryonic Rhabdomyosarcoma, Case report with brief ...

    African Journals Online (AJOL)

    Testicular Embryonic Rhabdomyosarcoma, Case report with brief literature review. AM Adam, MMAM Ibnouf, IAF Allah. Abstract. Background: Rhabdomyosarcoma (RMS) is a malignant solid tumour arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites.

  13. Tooth engineering: searching for dental mesenchymal cells sources.

    Directory of Open Access Journals (Sweden)

    Laetitia eKeller

    2011-03-01

    Full Text Available The implantation of cultured re-associations between embryonic dental mesenchymal cells and epithelial cells from mouse molars at ED14 allowed making full teeth with crown, root, periodontal ligament fibers and bone. Although representing valuable tools to set up methodologies embryonic cells are not easily available. This work thus aimed to replace the embryonic cells by dental mesenchymal cell lines or cultured expanded embryonic cells, and to test their ability to mediate tooth development in vitro when re-associated with a competent dental epithelium. Histology, immunostaining and RT-PCR allowed getting complementary sets of results. Two different immortalized cell lines from ED18 dental mesenchyme failed in mediating tooth formation. The potentialities of embryonic dental mesenchymal cells decreased from ED14 to ED16 and were lost at ED18. This is likely related to a change in the mesenchymal cell phenotype and/or populations during development. Attempts to cultivate ED14 or ED16 embryonic dental mesenchymal cells prior to re-association led to the loss of their ability to support tooth development. This was accompanied by a down-regulation of Fgf3 transcription. Supplementation of the culture medium with FGF2 allowed restoring Fgf3 expression, but not the ability of mesenchymal cells to engage in tooth formation. Altogether, these observations suggest that a competent cell population exists in the dental mesenchyme at ED14, progressively decreases during development, and cannot as such be maintained in vitro. This study evidenced the need for specific conditions to maintain the ability of dental mesenchymal cells to initiate whole tooth formation, when re-associated with an odontogenic epithelium. Efforts to improve the culture conditions will have to be combined with attempts to characterize the competent cells within the dental mesenchyme.

  14. Biomaterials and biologics in craniofacial reconstruction.

    Science.gov (United States)

    Engstrand, Thomas

    2012-01-01

    Complications related to surgery, including infection, wound dehiscence, and implant protrusion, are costly and may cause severe morbidity to patients. The choice of implants materials is critical for a successful outcome, particularly in craniofacial reconstructions. This review discusses the potential benefits and drawbacks of biologically active materials used for craniofacial bone repair as alternatives to inert implant prostheses.

  15. Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression.

    Science.gov (United States)

    Singh, Nikhil; Gupta, Mudit; Trivedi, Chinmay M; Singh, Manvendra K; Li, Li; Epstein, Jonathan A

    2013-05-15

    Craniofacial development is characterized by reciprocal interactions between neural crest cells and neighboring cell populations of ectodermal, endodermal and mesodermal origin. Various genetic pathways play critical roles in coordinating the development of cranial structures by modulating the growth, survival and differentiation of neural crest cells. However, the regulation of these pathways, particularly at the epigenomic level, remains poorly understood. Using murine genetics, we show that neural crest cells exhibit a requirement for the class I histone deacetylase Hdac3 during craniofacial development. Mice in which Hdac3 has been conditionally deleted in neural crest demonstrate fully penetrant craniofacial abnormalities, including microcephaly, cleft secondary palate and dental hypoplasia. Consistent with these abnormalities, we observe dysregulation of cell cycle genes and increased apoptosis in neural crest structures in mutant embryos. Known regulators of cell cycle progression and apoptosis in neural crest, including Msx1, Msx2 and Bmp4, are upregulated in Hdac3-deficient cranial mesenchyme. These results suggest that Hdac3 serves as a critical regulator of craniofacial morphogenesis, in part by repressing core apoptotic pathways in cranial neural crest cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Craniofacial imaging informatics and technology development.

    Science.gov (United States)

    Vannier, M W

    2003-01-01

    'Craniofacial imaging informatics' refers to image and related scientific data from the dentomaxillofacial complex, and application of 'informatics techniques' (derived from disciplines such as applied mathematics, computer science and statistics) to understand and organize the information associated with the data. Major trends in information technology determine the progress made in craniofacial imaging and informatics. These trends include industry consolidation, disruptive technologies, Moore's law, electronic atlases and on-line databases. Each of these trends is explained and documented, relative to their influence on craniofacial imaging. Craniofacial imaging is influenced by major trends that affect all medical imaging and related informatics applications. The introduction of cone beam craniofacial computed tomography scanners is an example of a disruptive technology entering the field. An important opportunity lies in the integration of biologic knowledge repositories with craniofacial images. The progress of craniofacial imaging will continue subject to limitations imposed by the underlying technologies, especially imaging informatics. Disruptive technologies will play a major role in the evolution of this field.

  17. The FaceBase Consortium: a comprehensive resource for craniofacial researchers

    Science.gov (United States)

    Brinkley, James F.; Fisher, Shannon; Harris, Matthew P.; Holmes, Greg; Hooper, Joan E.; Wang Jabs, Ethylin; Jones, Kenneth L.; Kesselman, Carl; Klein, Ophir D.; Maas, Richard L.; Marazita, Mary L.; Selleri, Licia; Spritz, Richard A.; van Bakel, Harm; Visel, Axel; Williams, Trevor J.; Wysocka, Joanna

    2016-01-01

    The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health, is designed to accelerate understanding of craniofacial developmental biology by generating comprehensive data resources to empower the research community, exploring high-throughput technology, fostering new scientific collaborations among researchers and human/computer interactions, facilitating hypothesis-driven research and translating science into improved health care to benefit patients. The resources generated by the FaceBase projects include a number of dynamic imaging modalities, genome-wide association studies, software tools for analyzing human facial abnormalities, detailed phenotyping, anatomical and molecular atlases, global and specific gene expression patterns, and transcriptional profiling over the course of embryonic and postnatal development in animal models and humans. The integrated data visualization tools, faceted search infrastructure, and curation provided by the FaceBase Hub offer flexible and intuitive ways to interact with these multidisciplinary data. In parallel, the datasets also offer unique opportunities for new collaborations and training for researchers coming into the field of craniofacial studies. Here, we highlight the focus of each spoke project and the integration of datasets contributed by the spokes to facilitate craniofacial research. PMID:27287806

  18. More are awaiting for craniofacial intervention

    International Nuclear Information System (INIS)

    Fan Xindong

    2006-01-01

    The scale of craniofacial intervention lies between the fields of neuro-intervention and peripheral interventional for the main purpose to investigate, diagnose and treat the disease entities originating from or supplied by the external carotid arterial system. Patients are usually refered to the oral and maxillofacial surgery, plastic surgery and otolaryngeal surgery. Craniofacial intervention includes mainly the diagnosis and treatment with adjuvant embolization of high-flow vascular diseases, intra-arterial chemotherapy of malignant tumors, embolization of epistaxis, etc. At present, there is no consensus with regard to the diagnosis and treatment of some craniofacial diseases, therefore further investigation and discussion are needed. (authors)

  19. Core issues in craniofacial myogenesis

    International Nuclear Information System (INIS)

    Kelly, Robert G.

    2010-01-01

    Branchiomeric craniofacial muscles control feeding, breathing and facial expression. These muscles differ on multiple counts from all other skeletal muscles and originate in a progenitor cell population in pharyngeal mesoderm characterized by a common genetic program with an adjacent population of cardiac progenitor cells, the second heart field, that gives rise to much of the heart. The transcription factors and signaling molecules that trigger the myogenic program at sites of branchiomeric muscle formation are correspondingly distinct from those in somite-derived muscle progenitor cells. Here new insights into the regulatory hierarchies controlling branchiomeric myogenesis are discussed. Differences in embryological origin are reflected in the lineage, transcriptional program and proliferative and differentiation properties of branchiomeric muscle satellite cells. These recent findings have important implications for our understanding of the diverse myogenic strategies operative both in the embryo and adult and are of direct biomedical relevance to deciphering the mechanisms underlying the cause and progression of muscle restricted myopathies.

  20. Orthognathic Surgery in Craniofacial Microsomia: Treatment Algorithm

    Science.gov (United States)

    Valladares, Salvador; Torrealba, Ramón; Nuñez, Marcelo; Uribe, Francisca

    2015-01-01

    Summary: Craniofacial microsomia is a broad term that covers a variety of craniofacial malformation conditions that are caused by alterations in the derivatives of the first and second pharyngeal arches. In general terms, diverse therapeutic alternatives are proposed according to the growth stage and the severity of the alteration. When craniofacial growth has concluded, conventional orthognathic surgery (Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty) provides good alternatives for MI and MIIA type cases. Reconstruction of the mandibular ramus and temporomandibular joint before orthognathic surgery is the indicated treatment for cases MIIB and MIII. The goal of this article is to establish a surgical treatment algorithm for orthognathic surgery on patients with craniofacial microsomia, analyzing the points that allow the ideal treatment for each patient to be chosen. PMID:25674375

  1. Growth Hormone and Craniofacial Tissues. An update

    OpenAIRE

    Litsas, George

    2015-01-01

    Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the ...

  2. Relationships between craniofacial pain and bruxism.

    Science.gov (United States)

    Svensson, P; Jadidi, F; Arima, T; Baad-Hansen, L; Sessle, B J

    2008-07-01

    A still commonly held view in the literature and clinical practice is that bruxism causes pain because of overloading of the musculoskeletal tissue and craniofacial pain, on the other hand, triggers more bruxism. Furthermore, it is often believed that there is a dose-response gradient so that more bruxism (intensity, duration) leads to more overloading and pain. Provided the existence of efficient techniques to treat bruxism, it would be straightforward in such a simple system to target bruxism as the cause of pain and hence treat the pain. Of course, human biological systems are much more complex and therefore, it is no surprise that the relationship between bruxism and pain is far from being simple or even linear. Indeed, there are unexpected relationships, which complicate the establishment of adequate explanatory models. Part of the reason is the complexity of the bruxism in itself, which presents significant challenges related to operationalized criteria and diagnostic tools and underlying pathophysiology issues, which have been dealt with in other reviews in this issue. However, another important reason is the multifaceted nature of craniofacial pain. This review will address our current understanding of classification issues, epidemiology and neurobiological mechanisms of craniofacial pain. Experimental models of bruxism may help to further the understanding of the relationship between craniofacial pain and bruxism in addition to insights from intervention studies. The review will enable clinicians to understand the reasons why simple cause-effect relationships between bruxism and craniofacial pain are inadequate and the current implications for management of craniofacial pain.

  3. Craniofacial and dental development in Costello syndrome.

    Science.gov (United States)

    Goodwin, Alice F; Oberoi, Snehlata; Landan, Maya; Charles, Cyril; Massie, Jessica C; Fairley, Cecilia; Rauen, Katherine A; Klein, Ophir D

    2014-06-01

    Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n = 41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development. © 2014 Wiley Periodicals, Inc.

  4. Engineering human cell spheroids to model embryonic tissue fusion in vitro.

    Science.gov (United States)

    Epithelial-mesenchymal interactions drive embryonic fusion events during development and upon perturbation can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known abo...

  5. Data for human cell spheroid model of embryonic tissue fusion in vitro.

    Data.gov (United States)

    U.S. Environmental Protection Agency — Epithelial-mesenchymal interactions drive embryonic fusion events during development and upon perturbation can result in birth defects. Cleft palate and neural tube...

  6. Craniofacial fibrous dysplasia: Report of a case using computed tomographic scan diagnosis

    Directory of Open Access Journals (Sweden)

    Nikhil Diwan

    2013-01-01

    Full Text Available Fibro-osseous lesions are benign mesenchymal tumors in which mineralized tissue, blood vessels, and giant cells, in varying proportions, replace normal bone. Although this group of lesions includes reactive lesions, harmatomas, and neoplasms, they cannot be distinguished only on the basis of the histopathology which can only confirm their common fibro-osseous nature. Definitive diagnosis requires thorough radiological evaluation. Computed tomographic images of craniofacial fibrous dysplasia on bone windows may be helpful and allow precise pre-operative diagnosis and surgical planning.

  7. The No. 3 Craniofacial Cleft

    OpenAIRE

    Sagiran, -

    2002-01-01

    Sumbing no.3 merupakan satu di antara 14 tipe kelainan sumbing kraniofasial kongenital. Lokasi sumbing ini bertepatan dengan tempat pertemuan antara proces¬sus maxillaris dan frontonasalis pada masa perkembangan embryonal. Mengetahui embryologi leher dan kepala memberi pemahaman mengenai fungsi saraf kepala, prinsip-prinsip pembentukan kepala-wajah dan kelainan-kelainannya yang merupakan akibat penyimpangan dari perkembangannya. Penanganan kelainan ini memerlukan bedah rekonstruksi yang cangg...

  8. The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery.

    Science.gov (United States)

    Mahon, Nicola A; Joyce, Cormac W; Thomas, Sangeetha; Concannon, Elizabeth; Murray, Dylan

    2015-09-01

    Citation analysis is a recognized scientometric method of classifying cited articles according to the frequency of which they have been referenced. The total number of citations an article receives is considered to reflect it's significance among it's peers. Until now, a bibliometric analysis has never been performed in the specialty of craniofacial anomalies and craniofacial surgery. This citation analysis generates an extensive list of the 50 most influential papers in this developing field. Journals specializing in craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery, genetics and pediatrics were searched to demonstrate which articles have cultivated the specialty within the past 55 years. The results show an intriguing compilation of papers which outline the fundamental knowledge of craniofacial anomalies and the developments of surgical techniques to manage these patients. This citation analysis provides a summation of the current most popular trends in craniofacial literature. These esteemed papers aid to direct our decision making today within this specialty.

  9. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

    Directory of Open Access Journals (Sweden)

    Limor Landsman

    2011-09-01

    Full Text Available The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an

  10. A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression

    Directory of Open Access Journals (Sweden)

    Amsterdam Adam

    2006-06-01

    Full Text Available Abstract Background Craniofacial birth defects result from defects in cranial neural crest (NC patterning and morphogenesis. The vertebrate craniofacial skeleton is derived from cranial NC cells and the patterning of these cells occurs within the pharyngeal arches. Substantial efforts have led to the identification of several genes required for craniofacial skeletal development such as the endothelin-1 (edn1 signaling pathway that is required for lower jaw formation. However, many essential genes required for craniofacial development remain to be identified. Results Through screening a collection of insertional zebrafish mutants containing approximately 25% of the genes essential for embryonic development, we present the identification of 15 essential genes that are required for craniofacial development. We identified 3 genes required for hyomandibular development. We also identified zebrafish models for Campomelic Dysplasia and Ehlers-Danlos syndrome. To further demonstrate the utility of this method, we include a characterization of the wdr68 gene. We show that wdr68 acts upstream of the edn1 pathway and is also required for formation of the upper jaw equivalent, the palatoquadrate. We also present evidence that the level of wdr68 activity required for edn1 pathway function differs between the 1st and 2nd arches. Wdr68 interacts with two minibrain-related kinases, Dyrk1a and Dyrk1b, required for embryonic growth and myotube differentiation, respectively. We show that a GFP-Wdr68 fusion protein localizes to the nucleus with Dyrk1a in contrast to an engineered loss of function mutation Wdr68-T284F that no longer accumulated in the cell nucleus and failed to rescue wdr68 mutant animals. Wdr68 homologs appear to exist in all eukaryotic genomes. Notably, we found that the Drosophila wdr68 homolog CG14614 could substitute for the vertebrate wdr68 gene even though insects lack the NC cell lineage. Conclusion This work represents a systematic

  11. Craniofacial Reconstruction Evaluation by Geodesic Network

    Directory of Open Access Journals (Sweden)

    Junli Zhao

    2014-01-01

    Full Text Available Craniofacial reconstruction is to estimate an individual’s face model from its skull. It has a widespread application in forensic medicine, archeology, medical cosmetic surgery, and so forth. However, little attention is paid to the evaluation of craniofacial reconstruction. This paper proposes an objective method to evaluate globally and locally the reconstructed craniofacial faces based on the geodesic network. Firstly, the geodesic networks of the reconstructed craniofacial face and the original face are built, respectively, by geodesics and isogeodesics, whose intersections are network vertices. Then, the absolute value of the correlation coefficient of the features of all corresponding geodesic network vertices between two models is taken as the holistic similarity, where the weighted average of the shape index values in a neighborhood is defined as the feature of each network vertex. Moreover, the geodesic network vertices of each model are divided into six subareas, that is, forehead, eyes, nose, mouth, cheeks, and chin, and the local similarity is measured for each subarea. Experiments using 100 pairs of reconstructed craniofacial faces and their corresponding original faces show that the evaluation by our method is roughly consistent with the subjective evaluation derived from thirty-five persons in five groups.

  12. Craniofacial ontogeny in Centrosaurus apertus

    Directory of Open Access Journals (Sweden)

    Joseph A. Frederickson

    2014-02-01

    Full Text Available Centrosaurus apertus, a large bodied ceratopsid from the Late Cretaceous of North America, is one of the most common fossils recovered from the Belly River Group. This fossil record shows a wide diversity in morphology and size, with specimens ranging from putative juveniles to fully-grown individuals. The goal of this study was to reconstruct the ontogenetic changes that occur in the craniofacial skeleton of C. apertus through a quantitative cladistic analysis. Forty-seven cranial specimens were independently coded in separate data matrices for 80 hypothetical multistate growth characters and 130 hypothetical binary growth characters. Both analyses yielded the max-limit of 100,000 most parsimonious saved trees and the strict consensus collapsed into large polytomies. In order to reduce conflict resulting from missing data, fragmentary individuals were removed and the analyses were rerun. Among both the complete and the reduced data sets the multistate analyses recovered a shorter tree with a higher consistency index (CI than the additive binary data sets. The arrangement within the trees shows a progression of specimens with a recurved nasal horn in the least mature individuals, followed by specimens with straight nasal horns in relatively more mature individuals, and finally specimens with procurved nasal horns in the most mature individuals. The most mature individuals are further characterized by the reduction of the cranial horn ornamentations in late growth stages, a trait that similarly occurs in the growth of other dinosaurs. Bone textural changes were found to be sufficient proxies for relative maturity in individuals that have not reached adult size. Additionally, frill length is congruent with relative maturity status and makes an acceptable proxy for ontogenetic status, especially in smaller individuals. In adult-sized individuals, the fusion of the epiparietals and episquamosals and the orientation of the nasal horn are the best

  13. Advances in Bioprinting Technologies for Craniofacial Reconstruction.

    Science.gov (United States)

    Visscher, Dafydd O; Farré-Guasch, Elisabet; Helder, Marco N; Gibbs, Susan; Forouzanfar, Tymour; van Zuijlen, Paul P; Wolff, Jan

    2016-09-01

    Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor site morbidity. These limitations have subsequently led to the development of less invasive techniques such as 3D bioprinting that could offer possibilities to manufacture patient-tailored bioactive tissue constructs for craniofacial reconstruction. Here, we discuss the current technological and (pre)clinical advances of 3D bioprinting for use in craniofacial reconstruction and highlight the challenges that need to be addressed in the coming years. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Discrimination among adults with craniofacial conditions.

    Science.gov (United States)

    Roberts, Rachel M

    2014-01-01

    The primary goal of this study was to establish the level of perceived discrimination experienced by adults with congenital craniofacial conditions in Australia and to examine predictors of discrimination. Specifically, this study tested whether social support mediates the relationship between discrimination and health. Adults (n = 93) who had been treated at the Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide for congenital craniofacial conditions (not including cleft lip and/or palate) completed questionnaires examining satisfaction with life, quality of life, anxiety and depression, self-esteem, satisfaction with social support, and satisfaction with appearance. A substantial minority of adults with congenital craniofacial conditions reported that they experience discrimination almost every day in a range of areas. Higher reports of discrimination were related to older age, being male, and less education. Other factors related to higher discrimination included lower levels of satisfaction with life, self-esteem, satisfaction with appearance and mental quality of life, as well as higher levels of anxiety and depression. Social support partially mediated the relationship between discrimination and mental health outcomes. The current study shows that discrimination experiences continue into adulthood confirming the importance of ensuring patients are well supported both by psychosocial services as well as within their own social support networks.

  15. Craniofacial orthodontics and postgraduate orthodontic training in ...

    African Journals Online (AJOL)

    The least clinical experience was recorded in pre-bone graft orthodontics (7.4%) and orthodontic preparation for orthognathic surgery (5.5%). Some of the challenges highlighted by the residents were low patients turn out for orthodontic care and the absence of multidisciplinary treatment for craniofacial patients in their ...

  16. Surgical treatment of craniofacial haemangioma in children

    African Journals Online (AJOL)

    Keywords: craniofacial area, haemangioma, surgical treatment ... Correspondence to Kamal Abdel-Elah Aly, Pediatric Surgery Unit, ..... Adverse effects of systemic glucocorticosteroid therapy in infants with hemangiomas. Arch Dermatol 2004; 140:963–969. 23 Siegfried EC, Keenan WJ, Al Jureidini S. More on propranolol ...

  17. Advances in bioprinting technologies for craniofacial reconstruction

    NARCIS (Netherlands)

    Visscher, D.O.; Farré-Guasch, E.; Helder, M.N.; Gibbs, S.; Forouzanfar, T.; van Zuijlen, P.P.; Wolff, J.

    2016-01-01

    Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor

  18. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression

    DEFF Research Database (Denmark)

    Cano, A; Pérez-Moreno, M A; Rodrigo, I

    2000-01-01

    The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas......, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt...

  19. Quantifying Normal Craniofacial Form and Baseline Craniofacial Asymmetry in the Pediatric Population.

    Science.gov (United States)

    Cho, Min-Jeong; Hallac, Rami R; Ramesh, Jananie; Seaward, James R; Hermann, Nuno V; Darvann, Tron A; Lipira, Angelo; Kane, Alex A

    2018-03-01

    Restoring craniofacial symmetry is an important objective in the treatment of many craniofacial conditions. Normal form has been measured using anthropometry, cephalometry, and photography, yet all of these modalities have drawbacks. In this study, the authors define normal pediatric craniofacial form and craniofacial asymmetry using stereophotogrammetric images, which capture a densely sampled set of points on the form. After institutional review board approval, normal, healthy children (n = 533) with no known craniofacial abnormalities were recruited at well-child visits to undergo full head stereophotogrammetric imaging. The children's ages ranged from 0 to 18 years. A symmetric three-dimensional template was registered and scaled to each individual scan using 25 manually placed landmarks. The template was deformed to each subject's three-dimensional scan using a thin-plate spline algorithm and closest point matching. Age-based normal facial models were derived. Mean facial asymmetry and statistical characteristics of the population were calculated. The mean head asymmetry across all pediatric subjects was 1.5 ± 0.5 mm (range, 0.46 to 4.78 mm), and the mean facial asymmetry was 1.2 ± 0.6 mm (range, 0.4 to 5.4 mm). There were no significant differences in the mean head or facial asymmetry with age, sex, or race. Understanding the "normal" form and baseline distribution of asymmetry is an important anthropomorphic foundation. The authors present a method to quantify normal craniofacial form and baseline asymmetry in a large pediatric sample. The authors found that the normal pediatric craniofacial form is asymmetric, and does not change in magnitude with age, sex, or race.

  20. [Diagnosis of facial and craniofacial asymmetry].

    Science.gov (United States)

    Arnaud, E; Marchac, D; Renier, D

    2001-10-01

    Craniofacial asymmetry is caused by various aetiologies but clinical examination remains the most important criteria since minor asymmetry is always present. The diagnosis can be confirmed by anthropometric measurements and radiological examinations but only severe asymmetries or asymmetries with an associated functional impairment should be treated. The treatment depends on the cause, and on the time of appearance. Congenital asymmetries might be treated early, during the first year of life if a craniosynostosis is present. Hemifacial microsomia are treated later if there is no breathing impairment. Since the pediatricians have recommended the dorsal position for infant sleeping, an increasing number of posterior flattening of the skull has been appearing, and could be prevented by adequate nursing. Other causes of craniofacial asymmetries are rare and should be adapted to the cause (tumors, atrophies, neurological paralysis, hypertrophies) by a specialized multidisciplinar team.

  1. CT Imaging of Craniofacial Fibrous Dysplasia

    Directory of Open Access Journals (Sweden)

    Zerrin Unal Erzurumlu

    2015-01-01

    Full Text Available Fibrous dysplasia is a benign fibroosseous bone dysplasia that can involve single (monostotic or multiple (polyostotic bones. Monostotic form is more frequent in the jaws. It is termed as craniofacial fibrous dysplasia, when it involves, though rarely, adjacent craniofacial bones. A 16-year-old girl consulted for a painless swelling in the right posterior mandible for two years. Panoramic radiography revealed ground-glass ill-defined lesions in the three different regions of the maxilla and mandible. Axial CT scan (bone window showed multiple lesions involving skull base and facial bones. Despite lesions in the skull base, the patient had no abnormal neurological findings. The lesion was diagnosed as fibrous dysplasia based on radiological and histopathological examination. In this paper, CT findings and differential diagnosis of CFD are discussed. CT is a useful imaging technique for CFD cases.

  2. Modeling of Craniofacial Anatomy, Variation, and Growth

    DEFF Research Database (Denmark)

    Thorup, Signe Strann

    The topic of this thesis is automatic analysis of craniofacial images with respect to changes due to growth and surgery, inter-subject variation and intracranial volume estimation. The methods proposed contribute to the knowledge about specific craniofacial anomalies, as well as provide a tool...... for detailed analyses for clinical and research purposes. Most of the applications in this thesis rely on non-rigid image registration by the means of warping one image into the coordinate system of another image. This warping results in a deformation field that describes the anatomical correspondence between......, thus creating a personalized atlas. The knowledge built into the atlas is e.g. location of anatomical regions and landmarks of importance to surgery planning and evaluation or population studies. With these correspondences, various analyses could be carried out e.g. quantification of growth, inter...

  3. Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia.

    Science.gov (United States)

    Yamanaka, S; Nakao, Kazumasa; Koyama, N; Isobe, Y; Ueda, Y; Kanai, Y; Kondo, E; Fujii, T; Miura, M; Yasoda, A; Nakao, Kazuwa; Bessho, K

    2017-12-01

    Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis. In this study, we analyzed craniofacial morphology in a mouse model of achondroplasia, in which fibroblast growth factor receptor 3 (FGFR3) is specifically activated in cartilage ( Fgfr3 ach mice), and investigated the mechanisms of jaw deformities caused by this mutation. Furthermore, we analyzed the effect of CNP on the maxillofacial area in these animals. Fgfr3 ach mice exhibited midfacial hypoplasia, especially in the sagittal direction, caused by impaired endochondral ossification in craniofacial cartilage and by premature closure of the spheno-occipital synchondrosis, an important growth center in craniomaxillofacial skeletogenesis. We crossed Fgfr3 ach mice with transgenic mice in which CNP is expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP ( Fgfr3 ach /SAP-Nppc-Tg mice). In the progeny, midfacial hypoplasia in the sagittal direction observed in Fgfr3 ach mice was improved significantly by restoring the thickness of synchondrosis and promoting proliferation of chondrocytes in the craniofacial cartilage. In addition, the foramen magnum stenosis observed in Fgfr3 ach mice was significantly ameliorated in Fgfr3 ach /SAP-Nppc-Tg mice due to enhanced endochondral bone growth of the anterior intraoccipital synchondrosis. These results clearly demonstrate the therapeutic

  4. Imaging findings in craniofacial childhood rhabdomyosarcoma

    International Nuclear Information System (INIS)

    Freling, Nicole J.M.; Rijn, Rick R. van; Merks, Johannes H.M.; Saeed, Peerooz; Balm, Alfons J.M.; Bras, Johannes; Pieters, Bradley R.; Adam, Judit A.

    2010-01-01

    Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3-5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed. (orig.)

  5. Etiology and treatment in craniofacial fractures

    Directory of Open Access Journals (Sweden)

    Mihail D. L.

    2017-08-01

    Full Text Available Introduction. Facial trauma remains an important pathology in present days because of its effects. Facial deformities and functional alteration affect patient’s life quality and his society reinsertion. First evaluation has to be thorough to avoid any secondary complications .This type of pathology involves a pluridisciplinary approach: ENT, OMF, neurosurgeon,plastic surgeon,intensive care doctor. Healing implies complex biological process .A healed bone is capable to perform normal duties without titanium plates help. Osteosynthesis allows a faster and correct recovery. Doctors need to possess profound knowledge with regard to anatomy and physiology and to be acquainted with the reconstructive methods used in craniofacial surgery. Material and methods. This study evaluates craniofacial trauma patients who suffered different types of surgical interventions at the ENT Clinic and OMF Department of Constanta County Hospital since January the 1st 2013 until June the 1st 2017. Results. The group involves 133 cases, both genders and all ages. These 2 elements play an important role in this pathology because of the fact that the vast majority of patients are young active males. The sex ratio in the study is 7:1. In most of cases, craniofacial traumas appear after aggressions and car accidents. The nose and mandibular are fractured in a higher percentage in comparison to other parts of facial structures. Discussions. Important and sensitive structures located at this level increase the risk of possible important and definitive damages.

  6. Susuks (charm needles) in the craniofacial region

    International Nuclear Information System (INIS)

    Nambiar, P.; Ibrahim, N.; Tandjung, Y.R.M.; Shanmuhasuntharam, P.

    2008-01-01

    We conducted a study to determine the numbers of susuks (charm needles) and their distribution in the craniofacial region of susuk wearers, and the sex, racial affiliation, and age of the wearers. In addition, we sought to determine whether the presence of susuks posed any potential hazard to patients undergoing magnetic resonance imaging (MRI). We studied various radiographs of 33 susuk wearers (age range, 33-69 years) and investigated the most common sites of insertion in the craniofacial region. A susuk was also suspended inside a 1.5-T MRI machine to determined whether it was attracted by the machine's magnet. The largest number of susuks that we observed in the craniofacial region was 39 pins, and susuks were particularly numerous in Malay Muslim women. Other sites with susuks were the maxillofacial region (except the temporomandibular region) and the forehead. The susuks showed no ferromagnetic characteristics. As susuks are made from gold, they are generally biocompatible with human tissue and do not cause problems to their wearers. Gold and the other minor metal constituents found in susuks have no ferromagnetic characteristics and therefore pose no hazard to patients undergoing MRI. (author)

  7. Postoperative infections in craniofacial reconstructive procedures.

    Science.gov (United States)

    Fialkov, J A; Holy, C; Forrest, C R; Phillips, J H; Antonyshyn, O M

    2001-07-01

    The rate of, and possible risk factors for, postoperative craniofacial infection is unclear. To investigate this problem, we reviewed 349 cases of craniofacial skeletal procedures performed from 1996 to 1999 at our institution. Infection rate was determined and correlated with the use of implants, operative site, and cause of deformity. The inclusion criteria consisted of all procedures requiring autologous or prosthetic implantation in craniofacial skeletal sites, as well as all procedures involving bone or cartilage resection, osteotomies, debridement, reduction and/or fixation. Procedures that did not involve bone or cartilage surgery were excluded. The criteria for diagnosis of infection included clinical confirmation and one or more of 1) intravenous or oral antibiotic treatment outside of the prophylactic surgical regimen; 2) surgical intervention for drainage, irrigation, and or debridement; and 3) microbiological confirmation. Among the 280 surgical cases that fit the inclusion criteria and had complete records, there were 23 cases of postoperative infection (8.2%). The most common site for postoperative infection was the mandible (infection rate = 16.7%). Multiple logistic regression analysis revealed gunshot wound to be the most significant predictor of postoperative infection. Additionally, porous polyethylene implantation through a transoral route was correlated with a significant risk of postoperative infection.

  8. Nanomaterials for Craniofacial and Dental Tissue Engineering.

    Science.gov (United States)

    Li, G; Zhou, T; Lin, S; Shi, S; Lin, Y

    2017-07-01

    Tissue engineering shows great potential as a future treatment for the craniofacial and dental defects caused by trauma, tumor, and other diseases. Due to the biomimetic features and excellent physiochemical properties, nanomaterials are of vital importance in promoting cell growth and stimulating tissue regeneration in tissue engineering. For craniofacial and dental tissue engineering, the frequently used nanomaterials include nanoparticles, nanofibers, nanotubes, and nanosheets. Nanofibers are attractive for cell invasion and proliferation because of their resemblance to extracellular matrix and the presence of large pores, and they have been used as scaffolds in bone, cartilage, and tooth regeneration. Nanotubes and nanoparticles improve the mechanical and chemical properties of scaffold, increase cell attachment and migration, and facilitate tissue regeneration. In addition, nanofibers and nanoparticles are also used as a delivery system to carry the bioactive agent in bone and tooth regeneration, have better control of the release speed of agent upon degradation of the matrix, and promote tissue regeneration. Although applications of nanomaterials in tissue engineering remain in their infancy with numerous challenges to face, the current results indicate that nanomaterials have massive potential in craniofacial and dental tissue engineering.

  9. Craniofacial abnormalities among patients with Edwards Syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano M. Rosa

    2013-09-01

    Full Text Available OBJECTIVE To determine the frequency and types of craniofacial abnormalities observed in patients with trisomy 18 or Edwards syndrome (ES. METHODS This descriptive and retrospective study of a case series included all patients diagnosed with ES in a Clinical Genetics Service of a reference hospital in Southern Brazil from 1975 to 2008. The results of the karyotypic analysis, along with clinical data, were collected from medical records. RESULTS: The sample consisted of 50 patients, of which 66% were female. The median age at first evaluation was 14 days. Regarding the karyotypes, full trisomy of chromosome 18 was the main alteration (90%. Mosaicism was observed in 10%. The main craniofacial abnormalities were: microretrognathia (76%, abnormalities of the ear helix/dysplastic ears (70%, prominent occiput (52%, posteriorly rotated (46% and low set ears (44%, and short palpebral fissures/blepharophimosis (46%. Other uncommon - but relevant - abnormalities included: microtia (18%, orofacial clefts (12%, preauricular tags (10%, facial palsy (4%, encephalocele (4%, absence of external auditory canal (2% and asymmetric face (2%. One patient had an initial suspicion of oculo-auriculo-vertebral spectrum (OAVS or Goldenhar syndrome. CONCLUSIONS: Despite the literature description of a characteristic clinical presentation for ES, craniofacial alterations may be variable among these patients. The OAVS findings in this sample are noteworthy. The association of ES with OAVS has been reported once in the literature.

  10. Predictors of mental health in adults with congenital craniofacial conditions attending the Australian craniofacial unit.

    Science.gov (United States)

    Roberts, R M; Mathias, J L

    2013-07-01

    Objective : Adults with craniofacial conditions experience more psychosocial problems than adults in the general population, but little is known about the factors that render a person more or less susceptible to these problems. Guided by research on adults with other conditions that affect appearance, this study examined predictors of psychosocial outcome in adults with craniofacial conditions. Design : Single-sample cross-sectional design. Setting : The Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide, one of the main craniofacial treatment centers in Australia. Participants : Adults (N  =  93; 36.9% of the potential sample) with congenital craniofacial conditions (excluding cleft lip and/or cleft palate) who were treated in the Australian Craniofacial Unit. Main Outcome Measures : All participants completed measures assessing anxiety, depression, and quality of life (Hospital Anxiety and Depression Scale, Short-Form Health Survey) and variables predicted to affect these outcomes (SF-36 Health Survey - Multidimensional Scale of Perceived Social Support, Rosenberg Self-Esteem Scale, Cleft Satisfaction Profile, Brief Fear of Negative Evaluation Scale, Derriford Appearance Scale). Results : Multiple regression analyses revealed that anxiety was predicted by social support, self-esteem, and fear of negative evaluation, while depression was predicted by self-esteem and social support. Physical quality of life was not predicted by any of the measures. Satisfaction with appearance, gender, age, and education were not related to outcome. Conclusions : Interventions designed to increase perceived social support and self-esteem and reduce fear of negative evaluation appear to be indicated and may assist in establishing a causal relationship between these variables.

  11. Top five craniofacial techniques for training in plastic surgery residency.

    Science.gov (United States)

    Fan, Kenneth; Kawamoto, Henry K; McCarthy, Joseph G; Bartlett, Scott P; Matthews, David C; Wolfe, S Anthony; Tanna, Neil; Vu, Minh-Thien; Bradley, James P

    2012-03-01

    Despite increasing specialization of craniofacial surgery, certain craniofacial techniques are widely applicable. The authors identified five such craniofacial techniques and queried American Society of Plastic Surgeons members and plastic surgery program directors regarding their comfort level with the procedures and their opinion on resident training for these selected procedures. First, a select group of senior craniofacial surgeons discussed and agreed on the top five procedures. Second, active American Society of Plastic Surgeons were surveyed regarding their opinion on training and their comfort level with each procedure. Third, plastic surgery residency program directors were studied to see which of the top five procedures are taught as part of the plastic surgery residency curriculum. The top five widely applicable craniofacial procedures are technically described and include the following: (1) cranial or iliac bone graft for nasal reconstruction, (2) perialar rim bone graft, (3) lateral canthopexy, (4) osseous genioplasty, and (5) bone graft harvest for orbital floor defects. For practicing plastic surgeons, comfort level in all procedures increased with advancing years in practice (except those with 75 percent), especially those with craniofacial fellowship training, felt competent in all procedures except osseous genioplasty (53 percent). Plastic surgery program directors agreed that all top five procedures should be mastered by graduation. Although program directors felt that all five selected craniofacial procedures should be taught and mastered during residency training, plastic surgeons without craniofacial fellowship training were less comfortable with the techniques. Residency training goals should include competence in core craniofacial techniques.

  12. Bioactive Sr(II/Chitosan/Poly(ε-caprolactone Scaffolds for Craniofacial Tissue Regeneration. In Vitro and In Vivo Behavior

    Directory of Open Access Journals (Sweden)

    Itzia Rodríguez-Méndez

    2018-03-01

    Full Text Available In craniofacial tissue regeneration, the current gold standard treatment is autologous bone grafting, however, it presents some disadvantages. Although new alternatives have emerged there is still an urgent demand of biodegradable scaffolds to act as extracellular matrix in the regeneration process. A potentially useful element in bone regeneration is strontium. It is known to promote stimulation of osteoblasts while inhibiting osteoclasts resorption, leading to neoformed bone. The present paper reports the preparation and characterization of strontium (Sr containing hybrid scaffolds formed by a matrix of ionically cross-linked chitosan and microparticles of poly(ε-caprolactone (PCL. These scaffolds of relatively facile fabrication were seeded with osteoblast-like cells (MG-63 and human bone marrow mesenchymal stem cells (hBMSCs for application in craniofacial tissue regeneration. Membrane scaffolds were prepared using chitosan:PCL ratios of 1:2 and 1:1 and 5 wt % Sr salts. Characterization was performed addressing physico-chemical properties, swelling behavior, in vitro biological performance and in vivo biocompatibility. Overall, the composition, microstructure and swelling degree (≈245% of scaffolds combine with the adequate dimensional stability, lack of toxicity, osteogenic activity in MG-63 cells and hBMSCs, along with the in vivo biocompatibility in rats allow considering this system as a promising biomaterial for the treatment of craniofacial tissue regeneration.

  13. Rare craniofacial clefts in Ibadan | Iyun | Nigerian Journal of Plastic ...

    African Journals Online (AJOL)

    Introduction: Congenital craniofacial clefts are anatomical distortions of the face and cranium with deficiencies of excess of tissue in a linear pattern. The exact incidence of craniofacial clefts is unknown because cases are rare and series tend to be small. The aim of this study is to document our experience with congenital ...

  14. Craniofacial dysmorphology: Studies in honor of Samuel Pruzansky

    International Nuclear Information System (INIS)

    Cohen, M.M.; Rollnick, B.R.

    1985-01-01

    This book contains 31 chapters. Some of the chapter titles are: Regional Specification of Cell-Specific Gene Expression During Craniofacial Development; Timing Cleft Palate Closure - Age Should Not Be the Sole Determinant; Excess of Parental Non-Righthandedness in Children with Right-Sided Cleft Lip: A Preliminary Report; and The Application of Roentgencephalometry to the Study of Craniofacial Anomalies

  15. Achondroplasia: Craniofacial manifestations and considerations in dental management

    OpenAIRE

    Al-Saleem, Afnan; Al-Jobair, Asma

    2010-01-01

    Achondroplasia is the most common form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of dental interest because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control require special precautions during dental management. Craniofacial manifestations and c...

  16. Orthodontics and foetal pathology: a personal view on craniofacial patterning

    DEFF Research Database (Denmark)

    Kjær, Inger

    2009-01-01

    This article summarizes the essentials of studies on the craniofacial skeleton performed over 17 years. It presents data from research into foetal pathology resulting in new views on craniofacial patterning and/or fields for further discussion. The fields described cover all areas seen on profile...

  17. OCT imaging of craniofacial anatomy in xenopus embryos (Conference Presentation)

    Science.gov (United States)

    Deniz, Engin; Jonas, Stephan M.; Griffin, John; Hooper, Michael C.; Choma, Michael A.; Khokha, Mustafa K.

    2016-03-01

    The etiology of craniofacial defects is incompletely understood. The ability to obtain large amounts of gene sequence data from families affected by craniofacial defects is opening up new ways to understand molecular genetic etiological factors. One important link between gene sequence data and clinical relevance is biological research into candidate genes and molecular pathways. We present our recent research using OCT as a nondestructive phenotyping modality of craniofacial morphology in Xenopus embryos, an important animal model for biological research in gene and pathway discovery. We define 2D and 3D scanning protocols for a standardized approach to craniofacial imaging in Xenopus embryos. We define standard views and planar reconstructions for visualizing normal anatomy and landmarks. We compare these views and reconstructions to traditional histopathology using alcian blue staining. In addition to being 3D, nondestructive, and having much faster throughout, OCT can identify craniofacial features that are lost during traditional histopathological preparation. We also identify quantitative morphometric parameters to define normative craniofacial anatomy. We also note that craniofacial and cardiac defects are not infrequently present in the same patient (e.g velocardiofacial syndrome). Given that OCT excels at certain aspects of cardiac imaging in Xenopus embryos, our work highlights the potential of using OCT and Xenopus to study molecular genetic factors that impact both cardiac and craniofacial development.

  18. Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media.

    Directory of Open Access Journals (Sweden)

    Makoto Fukuta

    Full Text Available Neural crest cells (NCCs are an embryonic migratory cell population with the ability to differentiate into a wide variety of cell types that contribute to the craniofacial skeleton, cornea, peripheral nervous system, and skin pigmentation. This ability suggests the promising role of NCCs as a source for cell-based therapy. Although several methods have been used to induce human NCCs (hNCCs from human pluripotent stem cells (hPSCs, such as embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs, further modifications are required to improve the robustness, efficacy, and simplicity of these methods. Chemically defined medium (CDM was used as the basal medium in the induction and maintenance steps. By optimizing the culture conditions, the combination of the GSK3β inhibitor and TGFβ inhibitor with a minimum growth factor (insulin very efficiently induced hNCCs (70-80% from hPSCs. The induced hNCCs expressed cranial NCC-related genes and stably proliferated in CDM supplemented with EGF and FGF2 up to at least 10 passages without changes being observed in the major gene expression profiles. Differentiation properties were confirmed for peripheral neurons, glia, melanocytes, and corneal endothelial cells. In addition, cells with differentiation characteristics similar to multipotent mesenchymal stromal cells (MSCs were induced from hNCCs using CDM specific for human MSCs. Our simple and robust induction protocol using small molecule compounds with defined media enabled the generation of hNCCs as an intermediate material producing terminally differentiated cells for cell-based innovative medicine.

  19. Craniofacial anthropometry in newborns of Sikkimese origin.

    Science.gov (United States)

    Sinha, P; Tamang, B K; Chakraborty, S

    2014-06-01

    Head and face dimensions vary according to race and geographical zone. Hereditary factors also greatly affect the size and shape of the head. There are important medical applications of craniofacial data specific to different racial and ethnic groups. Various cranial and facial anthropometric parameters were assessed in singleton, healthy, full-term newborns of Sikkimese origin in a tertiary care hospital in Sikkim, India. The data were then analysed to determine statistically significant differences between sexes. Forty-five newborns were included in the study. Both male and female newborns were observed to be hyperbrachycephalic and hyperleptoprosopic. The only significant difference between the sexes was in commissural length, which was observed to be greater in male newborns. Craniofacial parameters in Sikkimese newborns vary in comparison with those of other newborns from around the world. Larger studies are needed in order to reveal sex-related variations. Similar studies on various racial groups in North-East India are needed to establish standards for populations with East Asian features.

  20. Engineering bone tissue from human embryonic stem cells

    OpenAIRE

    Marolt, Darja; Campos, Iván Marcos; Bhumiratana, Sarindr; Koren, Ana; Petridis, Petros; Zhang, Geping; Spitalnik, Patrice F.; Grayson, Warren L.; Vunjak-Novakovic, Gordana

    2012-01-01

    In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the i...

  1. Craniofacial morphology in unoperated infants with isolated cleft palate. A cephalometric analysis in three projections

    DEFF Research Database (Denmark)

    Hermann, N.V.; Kreiborg, S.; Jensen, B.L.

    58th Annual Meeting of the American Cleft Palate-Craniofacial Association, Minneapolis, Craniofacial morphology, unoperated infants, isolated cleft palate, cephalometric analysis, three projections......58th Annual Meeting of the American Cleft Palate-Craniofacial Association, Minneapolis, Craniofacial morphology, unoperated infants, isolated cleft palate, cephalometric analysis, three projections...

  2. DIFFERENTIATION OF EMBRYONIC STEM CELLS: LESSONS FROM EMBRYONIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    EMOKE PALL

    2008-05-01

    Full Text Available Embryonic stem (ES cells, the undifferentiated cells of early embryos are established as permanent lines and are characterised by their self-renewal capacity and the ability to retain their developmental capacity in vivo and in vitro. The pluripotent properties of ES cells are the basis of gene targeting technologies used to create mutant mouse strains with inactivated genes by homologous recombination. There are several methods to induce the formation of EBs. One of them the formation by aggregating ES cells in hanging drops, using gravity as an aggregation force. This method presents the advantage of obtaining well-calibrated EBs almost identical in size. We used at our experiment the mouse ES cell line KA1/11/C3/C8 with a normal karyotype, at 14th passages. Immunohistochemical examination was aimed to identify tissue-restricted proteins for the two differentiated lineages: titin as a cell-specific antigen for cardiac and skeletal muscle, betaIII-tubulin for the neuronal differentiation, cytokeratin Endo-A (TROMA for the presence of mesenchymal progenitor cells, Oct-4 for the presence of the undifferentiated ES cells. The beating cardiac muscle clumps showed more synchronous rhythm than those seen in EBs obtained from suspension culture method, where the beating cardiac muscle clumps appeared later, had a lower frequency and were uneven. The synaptic networks of neuronal cells were best developed in EBs from suspension, compared to those observed in EBs from hanging-drop method.

  3. Cervical column morphology and craniofacial profiles in monozygotic twins.

    Science.gov (United States)

    Sonnesen, Liselotte; Pallisgaard, Carsten; Kjaer, Inger

    2008-02-01

    Previous studies have described the relationships between cervical column morphology and craniofacial morphology. The aims of the present study were to describe cervical column morphology in 38 pairs of adult monozygotic (MZ) twins, and compare craniofacial morphology in twins with fusions with craniofacial morphology in twins without fusion. Visual assessment of cervical column morphology and cephalometric measurements of craniofacial morphology were performed on profile radiographs. In the cervical column, fusion between corpora of the second and third vertebrae was registered as fusion. In the twin group, 8 twin pairs had fusion of the cervical column in both individuals within the pair (sub-group A), 25 pairs had no fusions (subgroup B), and in 5 pairs, cervical column morphology was different within the pair (subgroup C), as one twin had fusion and the other did not. Comparison of craniofacial profiles showed a tendency to increased jaw retrognathia, larger cranial base angle, and larger mandibular inclination in subgroup A than in subgroup B. The same tendency was observed within subgroup C between the individual twins with fusion compared with those without fusion. These results confirm that cervical fusions and craniofacial morphology may be interrelated in twins when analysed on profile radiographs. The study also documents that differences in cervical column morphology can occur in individuals within a pair of MZ twins. It illustrates that differences in craniofacial morphology between individuals within a pair of MZ twins can be associated with cervical fusion.

  4. Psychosocial functioning in adults with congenital craniofacial conditions.

    Science.gov (United States)

    Roberts, R M; Mathias, J L

    2012-05-01

    To examine the psychosocial functioning of adults with congenital craniofacial conditions relative to normative data. Single sample cross-sectional design. The Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide, which is one of the main craniofacial treatment centers in Australia. Adults (N  =  93) with congenital craniofacial conditions (excluding cleft lip/palate) who were treated in the Australian Craniofacial Unit. All participants completed self-report scales assessing health-related quality of life (SF-36); life satisfaction, anxiety, and depression (HADS); self-esteem (Rosenberg); appearance-related concerns; perceived social support; and social anxiety. Overall, participants were very similar in psychosocial function to the general population. However, adults with craniofacial conditions were less likely to be married and have children (females), were more likely to be receiving a disability pension, and reported more appearance-related concerns and less social support from friends. They also reported more limitations in both their social activities, due to physical or emotional problems, and usual role activities, because of emotional problems, as well as poorer mental health. These results give cause to be very positive about the long-term outcomes of children who are undergoing treatment for craniofacial conditions, while also identifying specific areas that interventions could target.

  5. Nitric oxide synthase-3 promotes embryonic development of atrioventricular valves.

    Directory of Open Access Journals (Sweden)

    Yin Liu

    Full Text Available Nitric oxide synthase-3 (NOS3 has recently been shown to promote endothelial-to-mesenchymal transition (EndMT in the developing atrioventricular (AV canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT and NOS3(-/- mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3(-/- compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3(-/- mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1(+ cells in the AV cushion were decreased in NOS3(-/- compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ, bone morphogenetic protein (BMP2 and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3(-/- compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency.

  6. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells.

    Directory of Open Access Journals (Sweden)

    Allyson E Kennedy

    Full Text Available Since electronic cigarette (ECIG introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product.

  7. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells.

    Science.gov (United States)

    Kennedy, Allyson E; Kandalam, Suraj; Olivares-Navarrete, Rene; Dickinson, Amanda J G

    2017-01-01

    Since electronic cigarette (ECIG) introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM) in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product.

  8. Three-dimensional cranio-facial computed tomography

    International Nuclear Information System (INIS)

    Pozzi Muccelli, R.; Stagul, F.; Pozzi Muccelli, F.; Zuiani, C.; Smathers, R.

    1986-01-01

    Computed tomography allows today to reconstruct three-dimensional (eD) images fram axial scans. The authors report their experience in cranio-facial pathology achived in two Departments of Radiology (University of Trieste, Italy and University of Standford, California). 3D images have been realized using two different softwares, one of which allows to reconstruct both soft tissue and bone structures. The application in maxillo-facial traumas, cranio-facial malformations and head tumours are disscussed. 3D images turned out to be very useful for the optimal visualization and for the spatial demostration of the lesion and have potential applications in cranio-facial surgery and radiotherapy

  9. Three-dimensional cranio-facial computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Pozzi Muccelli, R; Stagul, F; Pozzi Muccelli, F; Zuiani, C; Smathers, R

    1986-01-01

    Computed tomography allows today to reconstruct three-dimensional (eD) images fram axial scans. The authors report their experience in cranio-facial pathology achived in two Departments of Radiology (University of Trieste, Italy and University of Standford, California). 3D images have been realized using two different softwares, one of which allows to reconstruct both soft tissue and bone structures. The application in maxillo-facial traumas, cranio-facial malformations and head tumours are disscussed. 3D images turned out to be very useful for the optimal visualization and for the spatial demostration of the lesion and have potential applications in cranio-facial surgery and radiotherapy.

  10. Craniofacial Secular Change in Recent Mexican Migrants.

    Science.gov (United States)

    Spradley, Katherine; Stull, Kyra E; Hefner, Joseph T

    2016-01-01

    Research by economists suggests that recent Mexican migrants are better educated and have higher socioeconomic status (SES) than previous migrants. Because factors associated with higher SES and improved education can lead to positive secular changes in overall body form, secular changes in the craniofacial complex were analyzed within a recent migrant group from Mexico. The Mexican group represents individuals in the act of migration, not yet influenced by the American environment, and thus can serve as a starting point for future studies of secular change in this population group. The excavation of a historic Hispanic cemetery in Tucson, Arizona, also allows for a comparison between historic Hispanics and recent migrants to explore craniofacial trends over a broad time period, as both groups originate from Mexico. The present research addresses two main questions: (1) Are cranial secular changes evident in recent Mexican migrants? (2) Are historic Hispanics and recent Mexican migrants similar? By studying secular changes within a migrant population group, secular trends may be detected, which will be important for understanding the biological variation of the migrants themselves and will serve as a preliminary investigation of secular change within Mexican migrants. The comparison of a sample of recent Mexican migrants with a historic Hispanic sample, predominantly of Mexican origin, allows us to explore morphological similarities and differences between early and recent Mexicans within the United States. Vault and face size and a total of 82 craniofacial interlandmark distances were used to explore secular changes within the recent Mexican migrants (females, n = 38; males, n = 178) and to explore the morphological similarities between historic Hispanics (females, n = 54; males, n = 58) and recent migrants. Sexes were separated, and multivariate adaptive regression splines and basis splines (quadratic with one knot) were used to assess the direction and magnitude

  11. Obstetric significance of fetal craniofacial duplication. A case report.

    Science.gov (United States)

    Chervenak, F A; Pinto, M M; Heller, C I; Norooz, H

    1985-01-01

    Craniofacial duplication (diprosopus) is a rare form of conjoined twins. Whenever fetal hydrocephalus is diagnosed, a careful search for other anomalies, such as diprosopus, is mandatory. The obstetric management depends upon the time of the diagnosis.

  12. Associations between the Cervical Vertebral Column and Craniofacial Morphology

    DEFF Research Database (Denmark)

    Sonnesen, Ane Liselotte

    2010-01-01

    Aim. To summarize recent studies on morphological deviations of the cervical vertebral column and associations with craniofacial morphology and head posture in nonsyndromic patients and in patients with obstructive sleep apnoea (OSA). Design. In these recent studies, visual assessment of the cerv......Aim. To summarize recent studies on morphological deviations of the cervical vertebral column and associations with craniofacial morphology and head posture in nonsyndromic patients and in patients with obstructive sleep apnoea (OSA). Design. In these recent studies, visual assessment...... of the cervical vertebral column and cephalometric analysis of the craniofacial skeleton were performed on profile radiographs of subjects with neutral occlusion, patients with severe skeletal malocclusions and patients with OSA. Material from human triploid foetuses and mouse embryos was analysed histologically....... Results. Recent studies have documented associations between fusion of the cervical vertebral column and craniofacial morphology, including head posture in patients with severe skeletal malocclusions. Histological studies on prenatal material supported these findings. Conclusion. It is suggested...

  13. Involuntary craniofacial lingual movements in intensive care-acquired quadriplegia.

    Science.gov (United States)

    Cartagena, A M; Jog, M; Young, G B

    2012-02-01

    The syndrome of involuntary craniofacial lingual movements in the setting of acute intensive care-acquired quadriplegia (critical illness neuromyopathy) following sepsis-associated encephalopathy has not been previously described. We suggest a localization and treatment for this disabling condition. Three patients (2 female) from our center were quadriplegic from critical illness neuromyopathy when they developed involuntary craniofacial lingual movements following sepsis-associated encephalopathy. Extensive investigations failed to identify an etiology for the abnormal movements. Movements were of large amplitude, of moderate speed, and semi-rhythmic in the jaw, tongue, and palate, persistent and extremely bothersome to all patients. Injection with Botulinum toxin type A was very beneficial. Involuntary craniofacial lingual movements in the setting of flaccid quadriplegia following sepsis-associated encephalopathy are consistent with focal craniofacial brainstem myoclonus and constitutes a new syndrome. Botulinum toxin type A treatment maybe helpful in treatment.

  14. Craniofacial orthodontics and postgraduate orthodontic training in Nigeria.

    Science.gov (United States)

    Isiekwe, G I; Oguchi, C O; daCosta, O O; Utomi, I L

    2016-01-01

    Craniofacial orthodontics has been shown to be a critical component of the care of patients with craniofacial anomalies such as cleft lip and palate. Thus, the purpose of this study was to assess the perceptions and clinical experience in cleft and craniofacial care, of orthodontic residents in Nigeria. Questionnaires were sent out to orthodontic residents in the six Postgraduate Orthodontic Training Centers in the country at that time. The questionnaires were self-administered and covered areas in beliefs in cleft care and the clinical experience and challenges faced by the residents in the provision of craniofacial orthodontic care at their various institutions. Thirty-three respondents returned completed questionnaires, with a response rate of 97%. All the respondents believed that residents should be involved in cleft and craniofacial care. Postnatal counseling was the clinical procedure in which the residents reported the highest level of clinical experience (47.4%). The least clinical experience was recorded in pre-bone graft orthodontics (7.4%) and orthodontic preparation for orthognathic surgery (5.5%). Some of the challenges highlighted by the residents were low patients turn out for orthodontic care and the absence of multidisciplinary treatment for craniofacial patients in their centers. Orthodontic residents in Nigeria believe that they should be involved in the management of patients with craniofacial anomalies and cleft lip and palate. However, majority of the residents have limited clinical experience in the management of these patients. A lot more needs to be done, to expose orthodontic residents in training, to all aspects of the orthodontic and multidisciplinary team care required for the cleft/craniofacial patient.

  15. Applications of Computer Technology in Complex Craniofacial Reconstruction

    Directory of Open Access Journals (Sweden)

    Kristopher M. Day, MD

    2018-03-01

    Conclusion:. Modern 3D technology allows the surgeon to better analyze complex craniofacial deformities, precisely plan surgical correction with computer simulation of results, customize osteotomies, plan distractions, and print 3DPCI, as needed. The use of advanced 3D computer technology can be applied safely and potentially improve aesthetic and functional outcomes after complex craniofacial reconstruction. These techniques warrant further study and may be reproducible in various centers of care.

  16. Stem cells: Update and impact on craniofacial surgery

    OpenAIRE

    Levi, Benjamin; Glotzbach, Jason; Wong, Victor; Nelson, Emily; Hyun, Jeong; Wan, Derrick C.; Gurtner, Geoffrey C.; Longaker, Michael T.

    2012-01-01

    With the rapidly expanding field of tissue engineering, surgeons have been eager to apply these principles to craniofacial surgery. Tissue engineering strategies combine the use of a cell type placed on a scaffold and subsequently implanted in vivo to address a tissue defect or tissue dysfunction. In this review we will discuss the current clinical need for skeletal and soft tissue engineering faced by craniofacial surgeons and subsequently we will explore cell types and scaffold designs bein...

  17. Adult psychological functioning of individuals born with craniofacial anomalies.

    Science.gov (United States)

    Sarwer, D B; Bartlett, S P; Whitaker, L A; Paige, K T; Pertschuk, M J; Wadden, T A

    1999-02-01

    This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal.

  18. Telomere stability and telomerase in mesenchymal stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Graakjaer, Jesper; Kølvrå, Steen

    2008-01-01

    Telomeres are repetitive genetic material that cap and thereby protect the ends of chromosomes. Each time a cell divides, telomeres get shorter. Telomere length is mainly maintained by telomerase. This enzyme is present in high concentrations in the embryonic stem cells and in fast growing...... embryonic cells, and declines with age. It is still unclear to what extent there is telomerase in adult stem cells, but since these are the founder cells of cells of all the tissues in the body, understanding the telomere dynamics and expression of telomerase in adult stem cells is very important....... In the present communication we focus on telomere expression and telomere length in stem cells, with a special focus on mesenchymal stem cells. We consider different mechanisms by which stem cells can maintain telomeres and also focus on the dynamics of telomere length in mesenchymal stem cells, both the overall...

  19. Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome.

    Science.gov (United States)

    Eason, Jessica; Williams, Antionette L; Chawla, Bahaar; Apsey, Christian; Bohnsack, Brenda L

    2017-09-01

    Ethanol (ETOH) exposure during pregnancy is associated with craniofacial and neurologic abnormalities, but infrequently disrupts the anterior segment of the eye. In these studies, we used zebrafish to investigate differences in the teratogenic effect of ETOH on craniofacial, periocular, and ocular neural crest. Zebrafish eye and neural crest development was analyzed by means of live imaging, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, immunostaining, detection of reactive oxygen species, and in situ hybridization. Our studies demonstrated that foxd3-positive neural crest cells in the periocular mesenchyme and developing eye were less sensitive to ETOH than sox10-positive craniofacial neural crest cells that form the pharyngeal arches and jaw. ETOH increased apoptosis in the retina, but did not affect survival of periocular and ocular neural crest cells. ETOH also did not increase reactive oxygen species within the eye. In contrast, ETOH increased ventral neural crest apoptosis and reactive oxygen species production in the facial mesenchyme. In the eye and craniofacial region, sod2 showed high levels of expression in the anterior segment and in the setting of Sod2 knockdown, low levels of ETOH decreased migration of foxd3-positive neural crest cells into the developing eye. However, ETOH had minimal effect on the periocular and ocular expression of transcription factors (pitx2 and foxc1) that regulate anterior segment development. Neural crest cells contributing to the anterior segment of the eye exhibit increased ability to withstand ETOH-induced oxidative stress and apoptosis. These studies explain the rarity of anterior segment dysgenesis despite the frequent craniofacial abnormalities in fetal alcohol syndrome. Birth Defects Research 109:1212-1227, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Current state of craniofacial prosthetic rehabilitation.

    Science.gov (United States)

    Ariani, Nina; Visser, Anita; van Oort, Robert P; Kusdhany, Lindawati; Rahardjo, Tri Budi W; Krom, Bastiaan P; van der Mei, Henry C; Vissink, Arjan

    2013-01-01

    This study aimed to review the current state of the techniques and materials used to rehabilitate maxillofacial defects. The MEDLINE and EMBASE databases were searched for articles pertinent to maxillofacial prostheses published from January 1990 to July 2011. The main clinical stages were the subject of analysis. A multidisciplinary approach is preferred when rehabilitating maxillofacial defects. Surgical reconstruction can be used for smaller defects, but larger defects require a prosthesis to achieve an esthetic rehabilitation. Implant retained prostheses are preferred over adhesive prostheses. Silicone elastomer is currently the best material available for maxillofacial prostheses; however, longevity and discoloration, which are greatly influenced by ultraviolet radiation, microorganisms, and environmental factors, remain significant problems. In the near future, the widespread availability and cost effectiveness of digital systems may improve the workflow and outcomes of facial prostheses. Patients report high satisfaction with their prostheses despite some areas that still need improvement. Maxillofacial prostheses are a reliable treatment option to restore maxillofacial defects and improve quality of life. Significant progress has been made in the application of implants for retention and digital technology for designing surgical guides, suprastructures, and craniofacial prostheses. Further improvements are necessary to enhance longevity of prostheses.

  1. Craniofacial morphology in Turner syndrome patients treated with growth hormone

    Directory of Open Access Journals (Sweden)

    Jovana Julsoki

    2015-05-01

    Full Text Available ABSTRACT Introduction: In addition to well-established physical characteristics, Turner syndrome patients have distinct craniofacial morphology. Since short stature is the most typical characteristic, Turner syndrome patients are commonly treated with growth hormone in order to increase final height. At the same time, growth hormone treatment was found to influence craniofacial growth and morphology in various groups of treated patients. Whereas craniofacial characteristics of Turner syndrome patients are well documented, comparatively little is known of craniofacial morphology of those who are treated with growth hormone. Aim: The aim of this study was to investigate craniofacial morphology in Turner syndrome patients treated with growth hormone in comparison to healthy females. Materials and methods: The cephalometric evaluation was conducted on twenty lateral cephalograms of Turner syndrome patients (13.53 ± 4.04 years treated with growth hormone for at least one year (4.94 ± 1.92 years in average. As a control group, forty lateral cephalograms of healthy female controls, who matched Turner syndrome patients by chronological (11.80 ± 2.37 years and skeletal age, were used. Eleven angular, seven linear measurements and six dimensional ratios were measured to describe craniofacial morphology. Results: The results obtained for angular measurements, in cephalometric analyses for Turner syndrome patients treated with growth hormone, revealed bimaxillary retrognathism. The linear measurements indicated longer mandibular ramus, anterior cranial base and both anterior and posterior facial heights. However, posterior cranial base and maxilla were in proportion to the anterior cranial base, when comparing dimensional ratios. Anterior cranial base, maxilla and mandibular ramus were larger in proportion to mandibular body; as well as posterior facial height was when compared to anterior facial height. Turner syndrome patients treated with growth

  2. Intraflagellar transport 88 (IFT88) is crucial for craniofacial development in mice and is a candidate gene for human cleft lip and palate.

    Science.gov (United States)

    Tian, Hua; Feng, Jifan; Li, Jingyuan; Ho, Thach-Vu; Yuan, Yuan; Liu, Yang; Brindopke, Frederick; Figueiredo, Jane C; Magee, William; Sanchez-Lara, Pedro A; Chai, Yang

    2017-03-01

    Ciliopathies are pleiotropic human diseases resulting from defects of the primary cilium, and these patients often have cleft lip and palate. IFT88 is required for the assembly and function of the primary cilia, which mediate the activity of key developmental signaling pathways. Through whole exome sequencing of a family of three affected siblings with isolated cleft lip and palate, we discovered that they share a novel missense mutation in IFT88 (c.915G > C, p.E305D), suggesting this gene should be considered a candidate for isolated orofacial clefting. In order to evaluate the function of IFT88 in regulating craniofacial development, we generated Wnt1-Cre;Ift88fl/fl mice to eliminate Ift88 specifically in cranial neural crest (CNC) cells. Wnt1-Cre;Ift88fl/flpups died at birth due to severe craniofacial defects including bilateral cleft lip and palate and tongue agenesis, following the loss of the primary cilia in the CNC-derived palatal mesenchyme. Loss of Ift88 also resulted in a decrease in neural crest cell proliferation during early stages of palatogenesis as well as a downregulation of the Shh signaling pathway in the palatal mesenchyme. Importantly, Osr2KI-Cre;Ift88fl/flmice, in which Ift88 is lost specifically in the palatal mesenchyme, exhibit isolated cleft palate. Taken together, our results demonstrate that IFT88 has a highly conserved function within the primary cilia of the CNC-derived mesenchyme in the lip and palate region in mice and is a strong candidate as an orofacial clefting gene in humans. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Cranio-facial clefts in pre-hispanic America.

    Science.gov (United States)

    Marius-Nunez, A L; Wasiak, D T

    2015-10-01

    Among the representations of congenital malformations in Moche ceramic art, cranio-facial clefts have been portrayed in pottery found in Moche burials. These pottery vessels were used as domestic items during lifetime and funerary offerings upon death. The aim of this study was to examine archeological evidence for representations of cranio-facial cleft malformations in Moche vessels. Pottery depicting malformations of the midface in Moche collections in Lima-Peru were studied. The malformations portrayed on pottery were analyzed using the Tessier classification. Photographs were authorized by the Larco Museo.Three vessels were observed to have median cranio-facial dysraphia in association with midline cleft of the lower lip with cleft of the mandible. ML001489 portrays a median cranio-facial dysraphia with an orbital cleft and a midline cleft of the lower lip extending to the mandible. ML001514 represents a median facial dysraphia in association with an orbital facial cleft and a vertical orbital dystopia. ML001491 illustrates a median facial cleft with a soft tissue cleft. Three cases of midline, orbital and lateral facial clefts have been portrayed in Moche full-figure portrait vessels. They represent the earliest registries of congenital cranio-facial malformations in ancient Peru. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Three-dimensional spiral CT of craniofacial malformations in children

    International Nuclear Information System (INIS)

    Binaghi, S.; Gudinchet, F.

    2000-01-01

    Objective. To assess the value of three-dimensional CT (3D CT) in the diagnosis and management of suspected paediatric craniofacial malformations. Materials and methods. Twenty-eight children (12 girls, 16 boys) with a mean age of 4 years, suffering from craniofacial or cervical malformations, underwent craniofacial spiral CT. 3D reformatting was performed using an independent workstation. Results. 3D CT allowed the preoperative evaluation of 16 patients with craniosynostosis and the post-surgical management of 2 patients. 3D CT clearly depicted malformations of the skull base involving the petrous bone in seven patients (four cases of Goldenhar-Gorlin syndrome, one case of Treacher-Collins syndrome and two cases of Crouzon's disease). Four patients with craniofacial clefts were also evaluated. Radiological findings were confirmed by the clinical and intraoperative findings in all patients that underwent surgical treatment. Movement artefacts and ''Lego effect'' related to abrupt change of cranial vault border were encountered and are discussed. Conclusions. 3D CT of the skull can safely and reliably identify paediatric craniofacial malformations involving bone, and it should be used as morphological mapping to help the surgeon in planning surgical treatment. (orig.)

  5. 75 FR 62553 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

    Science.gov (United States)

    2010-10-12

    ... Craniofacial Research Special Emphasis Panel, Secondary Data Analysis R03s: Special Emphasis Panel. Date... Craniofacial Research Special Emphasis Panel, Special Emphasis Panel: Secondary Data Analysis R03s. Date...

  6. Analysis of Practice Settings for Craniofacial Surgery Fellowship Graduates in North America.

    Science.gov (United States)

    Silvestre, Jason; Runyan, Christopher; Taylor, Jesse A

    In North America, the number of craniofacial surgery fellowship graduates is increasing, yet an analysis of practice settings upon graduation is lacking. We characterize the practice types of recent graduates of craniofacial fellowship programs in the United States and Canada. A 6-year cohort of craniofacial fellows in the United States and Canada (2010-2016) were obtained from craniofacial programs recognized by the American Society of Craniofacial Surgery. Practice setting was determined at 1 and 3 years of postgraduation, and predictors of practice setting were determined. A total of 175 craniofacial surgeons were trained at 35 fellowship programs. At 1 year of postgraduation, 33.6% had an academic craniofacial position and 27.1% were in private practice (p = 0.361). A minority of graduates pursued additional fellowships (16.4%), nonacademic craniofacial positions (10.0%), academic noncraniofacial positions (5.7%), and international practices (7.1%). At 3 years of postgraduation, the percentage of graduates in academic craniofacial positions was unchanged (34.5% vs 33.6%, p = 0.790). The strongest predictors of future academic craniofacial practice were completing plastic surgery residency at a program with a craniofacial fellowship program (odds ratio = 6.78, p < 0.001) and completing an academic craniofacial fellowship program (odds ratio = 4.48, p = 0.020). A minority of craniofacial fellowship graduates practice academic craniofacial surgery. A strong academic craniofacial surgery background during residency and fellowship is associated with a future career in academic craniofacial surgery. These data may assist trainees choose training programs that align with career goals and educators select future academic surgeons. Copyright © 2017. Published by Elsevier Inc.

  7. FGF8 signaling sustains progenitor status and multipotency of cranial neural crest-derived mesenchymal cells in vivo and in vitro

    Science.gov (United States)

    Shao, Meiying; Liu, Chao; Song, Yingnan; Ye, Wenduo; He, Wei; Yuan, Guohua; Gu, Shuping; Lin, Congxin; Ma, Liang; Zhang, Yanding; Tian, Weidong; Hu, Tao; Chen, YiPing

    2015-01-01

    The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive signals. However, what sustains the multipotency of CNC cells and derivatives remains largely unknown. In this study, we present evidence that FGF8 signaling is able to sustain progenitor status and multipotency of CNC-derived mesenchymal cells both in vivo and in vitro. We show that augmented FGF8 signaling in pre-migratory CNC cells prevents cell differentiation and organogenesis in the craniofacial region by maintaining their progenitor status. CNC-derived mesenchymal cells with Fgf8 overexpression or control cells in the presence of exogenous FGF8 exhibit prolonged survival, proliferation, and multi-potent differentiation capability in cell cultures. Remarkably, exogenous FGF8 also sustains the capability of CNC-derived mesenchymal cells to participate in organogenesis such as odontogenesis. Furthermore, FGF8-mediated signaling strongly promotes adipogenesis but inhibits osteogenesis of CNC-derived mesenchymal cells in vitro. Our results reveal a specific role for FGF8 in the maintenance of progenitor status and in fate determination of CNC cells, implicating a potential application in expansion and fate manipulation of CNC-derived cells in stem cell-based craniofacial regeneration. PMID:26243590

  8. [Observational study of craniofacial growth and development in Mexican children].

    Science.gov (United States)

    Fijikami, T K; Cedeño Pacheco, E

    1991-01-01

    The election of a investigation about craniofacial growing and development in Mexican children, was done due to a lack of national information in this rubric and as a fundamental part of the "growing and development in the scholastic" module of the Universidad Autónoma Metropolitana-Xochimilco, which work hypothesis was that "craniofacial growing and development in Mexican, 6 to 12 children in Xochimilco area are due to nutritional deficiency, second dentition eruption delay and dental maloclution "which was totality confirmed in a 100 Mexican facial characteristic children field work study, with cephalometric studies which permit to determine the craniofacial growing standard. This study was corroborated with a 40 children, 4 years later follow up.

  9. Analysis of Craniofacial Images using Computational Atlases and Deformation Fields

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur

    2008-01-01

    purposes. The basis for most of the applications is non-rigid image registration. This approach brings one image into the coordinate system of another resulting in a deformation field describing the anatomical correspondence between the two images. A computational atlas representing the average anatomy...... of asymmetry. The analyses are applied to the study of three different craniofacial anomalies. The craniofacial applications include studies of Crouzon syndrome (in mice), unicoronal synostosis plagiocephaly and deformational plagiocephaly. Using the proposed methods, the thesis reveals novel findings about...... the craniofacial morphology and asymmetry of Crouzon mice. Moreover, a method to plan and evaluate treatment of children with deformational plagiocephaly, based on asymmetry assessment, is established. Finally, asymmetry in children with unicoronal synostosis is automatically assessed, confirming previous results...

  10. Growth hormone therapy and craniofacial bones: a comprehensive review.

    Science.gov (United States)

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Porcine embryonic stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2008-01-01

    The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences...

  12. Automated analysis of craniofacial morphology using magnetic resonance images.

    Directory of Open Access Journals (Sweden)

    M Mallar Chakravarty

    Full Text Available Quantitative analysis of craniofacial morphology is of interest to scholars working in a wide variety of disciplines, such as anthropology, developmental biology, and medicine. T1-weighted (anatomical magnetic resonance images (MRI provide excellent contrast between soft tissues. Given its three-dimensional nature, MRI represents an ideal imaging modality for the analysis of craniofacial structure in living individuals. Here we describe how T1-weighted MR images, acquired to examine brain anatomy, can also be used to analyze facial features. Using a sample of typically developing adolescents from the Saguenay Youth Study (N = 597; 292 male, 305 female, ages: 12 to 18 years, we quantified inter-individual variations in craniofacial structure in two ways. First, we adapted existing nonlinear registration-based morphological techniques to generate iteratively a group-wise population average of craniofacial features. The nonlinear transformations were used to map the craniofacial structure of each individual to the population average. Using voxel-wise measures of expansion and contraction, we then examined the effects of sex and age on inter-individual variations in facial features. Second, we employed a landmark-based approach to quantify variations in face surfaces. This approach involves: (a placing 56 landmarks (forehead, nose, lips, jaw-line, cheekbones, and eyes on a surface representation of the MRI-based group average; (b warping the landmarks to the individual faces using the inverse nonlinear transformation estimated for each person; and (3 using a principal components analysis (PCA of the warped landmarks to identify facial features (i.e. clusters of landmarks that vary in our sample in a correlated fashion. As with the voxel-wise analysis of the deformation fields, we examined the effects of sex and age on the PCA-derived spatial relationships between facial features. Both methods demonstrated significant sexual dimorphism in

  13. The fourth dimension in simulation surgery for craniofacial surgical procedures.

    Science.gov (United States)

    Kurihara, T

    2001-03-01

    The intracranial volume was measured in all 18 cases of craniosynostosis and craniofacial synostosis with 3DCT using a modification of Miyake's formula, with a 6 years' follow-up. 1: There were no cases where the intracranial volume was less than the modified Miyake's formula. 2: Total cranial reshaping, compared to the local forehead advancement, was effective in increasing the intracranial cavity and growth postoperatively. 3: In cases of craniofacial synostosis, there is a possibility that mental retardation will develop if the intracranial volume tends to increase rapidly and more than expected.

  14. Complications in paediatric craniofacial surgery: an initial four year experience.

    Science.gov (United States)

    Jones, B M; Jani, P; Bingham, R M; Mackersie, A M; Hayward, R

    1992-04-01

    107 children undergoing transcranial craniofacial surgery in a paediatric hospital have been reviewed to assess the incidence and type of complications which arose. This represents the first 4 years' experience of the craniofacial team. There were no deaths or permanent adverse sequelae of surgery. A total of 53 complications were seen in 42 patients. In 9.3% of patients they were potentially life-threatening, serious in 12.1% and of a minor nature in 28%. The more serious complications were related either to haemorrhage and/or vasovagal shock at operation or to infection post-operatively. Infants undergoing monoblock frontofacial advancements and those with tracheostomies were at particular risk.

  15. Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.

    Science.gov (United States)

    Milstone, Zachary J; Lawson, Grace; Trivedi, Chinmay M

    2017-12-01

    Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown. The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch. Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches by means of repression of cyclin-dependent kinase inhibitors. Developmental Dynamics 246:1015-1026, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Msx-2 expression and glucocorticoid-induced overexpression in embryonic mouse submandibular glands.

    Science.gov (United States)

    Jaskoll, T; Luo, W; Snead, M L

    1998-01-01

    It is well known that the process of branching morphogenesis requires epithelial-mesenchymal interactions. One outstanding model for the study of tissue interactions during branching morphogenesis is the embryonic mouse submandibular gland (SMG). Although it has been clearly demonstrated that the branching pattern is dependent on interactions between the epithelium and the surrounding mesenchyme, little is known about the molecular mechanism underlying the branching process. One group of transcription factors that likely participates in the control of epithelial-mesenchymal inductive interactions are the Msx-class of homeodomain-containing proteins. In this paper, we focus on Msx-2 because its developmental expression is correlated with inductive interactions, suggesting that Msx-2 may play a functional role during cell-cell interactions. We demonstrate the expression of Msx-2 mRNA and protein to be primarily in the branching epithelia with progressive embryonic (E13 to E15) SMG development and, to a lesser extent, in the mesenchyme. We also show that Msx-2 is expressed by embryonic SMG primordia cultured under defined conditions. In addition, to begin to delineate a functional role for Msx-2, we employed an experimental strategy by using exogenous glucocorticoid (CORT) treatment of embryonic SMGs in vitro and in vivo to significantly enhance branching morphogenesis and evaluate the effect of CORT treatment on embryonic SMG Msx-2 expression. A marked increase in Msx-2 transcripts and protein is detected with in vitro and in vivo CORT treatment. Our studies indicate that one mechanism of CORT regulation of salivary gland morphogenesis is likely through the modulation of Msx-2 gene expression.

  17. Uterine mesenchymal tumors

    Directory of Open Access Journals (Sweden)

    Nikhil A Sangle

    2011-01-01

    Full Text Available Uterine mesenchymal tumors are a heterogeneous group of neoplasms that can frequently be diagnostically challenging. Differentiation between the benign and malignant counterparts of mesenchymal tumors is significant due to differences in clinical outcome, and the role of the surgical pathologist in making this distinction (especially in the difficult cases cannot be underestimated. Although immunohistochemical stains are supportive toward establishing a final diagnosis, the morphologic features trump all the other ancillary techniques for this group of neoplasms. This review therefore emphasizes the key morphologic features required to diagnose and distinguish uterine mesenchymal tumors from their mimics, with a brief description of the relevant immunohistochemical features.

  18. CRANIOFACIAL MORPHOLOGY AND DENTAL OCCLUSION IN ADULTS WITH OSTEOGENESIS IMPERFECTA

    DEFF Research Database (Denmark)

    Gjørup, Hans; Hald, Jannie Dahl; Harsløf, Torben

    AIMS: To compare craniofacial characteristics and variation in dental occlusion according to severity of osteogenesis imperfecta (OI). OI is a rare inherited disease with fragility of bone and teeth because of abnormalities in the formation of collagen. METHODS: A total of 73 patients...

  19. Craniofacial and temporal bone CT findings in cleidocranial dysplasia

    International Nuclear Information System (INIS)

    Gonzalez, Guido E.; Caruso, Paul A.; Curtin, Hugh D.; Small, Juan E.; Jyung, Robert W.; Troulis, Maria J.

    2008-01-01

    Cleidocranial dysplasia (CCD) is a multistructural polyostotic genetic disorder that results from mutation of the CBFA1 gene. Hearing loss is a frequent finding in CCD. We describe the CT craniofacial findings in CCD and provide a comprehensive discussion of the CT temporal bone findings in these patients. (orig.)

  20. Growth hormone positive effects on craniofacial complex in Turner syndrome.

    Science.gov (United States)

    Juloski, Jovana; Dumančić, Jelena; Šćepan, Ivana; Lauc, Tomislav; Milašin, Jelena; Kaić, Zvonimir; Dumić, Miroslav; Babić, Marko

    2016-11-01

    Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Academic Productivity of Faculty Associated With Craniofacial Surgery Fellowship Programs.

    Science.gov (United States)

    Ruan, Qing Zhao; Ricci, Joseph A; Silvestre, Jason; Ho, Olivia A; Ganor, Oren; Lee, Bernard T

    2017-11-01

    The H-index is increasingly being used as a measure of academic productivity and has been applied to various surgical disciplines. Here the authors calculate the H-index of craniofacial surgery fellowship faculty in North America in order to determine its utility for academic productivity among craniofacial surgeons. A list of fellowship programs was obtained from the website of the American Society of Craniofacial Surgery. Faculty demographics and institution characteristics were obtained from official program websites and the H-index was calculated using Scopus (Elsevier, USA). Data were assessed using bivariate analysis tools (Kruskal-Wallis and Mann-Whitney tests) to determine the relationship between independent variables and career publications, H-index and 5-year H-index (H5-index) of faculty. Dunn test for multiple comparisons was also calculated. A total of 102 faculty members from 29 craniofacial surgery fellowship programs were identified and included. Faculty demographics reflected a median age of 48 (interquartile range [IQR] 13), a predominantly male sample (88/102, 89.7%), and the rank of assistant professor being the most common among faculty members (41/102, 40.2%). Median of career publications per faculty was 37 (IQR 52.5) and medians of H-index and H5-index were 10.0 (IQR 13.75) and 3.5 (IQR 3.25), respectively. Greater age, male gender, Fellow of the American College of Surgeons membership, higher academic rank, and program affiliation with ranked research medical schools were significantly associated with higher H-indices. Variables associated with seniority were positively associated with the H-index. These results suggest that the H-index may be used as an adjunct in determining academic productivity for promotions among craniofacial surgeons.

  2. Craniofacial CT findings of Gorham-Stout disease and generalized lymphatic anomaly

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroki; Matsuo, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Ozeki, Michio; Fukao, Toshiyuki [Gifu University School of Medicine, Department of Pediatrics, Gifu (Japan)

    2016-08-15

    The present study aimed to assess the craniofacial CT imaging features for differentiating between Gorham-Stout disease (GSD) and generalized lymphatic anomaly (GLA). Seven patients with GSD and four patients with GLA were included in this study. All patients underwent CT examinations that encompassed the craniofacial bones. The presence, distribution, and type of craniofacial osteolysis were assessed. The clinical symptoms that were associated with craniofacial osteolysis were also reviewed. Craniofacial osteolysis including cranial osteolysis was seen in four of seven (57 %) patients with GSD and in three of four (75 %) patients with GLA. Facial osteolysis was seen in two (29 %) patients with GSD, but this was not observed in patients with GLA. Among patients with craniofacial osteolysis, those with GSD showed diffuse involvement, whereas those with GLA showed multifocal involvement. The craniofacial osteolysis of GSD could be classified into three patterns: medullary involvement, thinning bone, and disappearing bone. The clinical symptoms of craniofacial osteolysis were observed in all patients with GSD but were not present in patients with GLA. Craniofacial involvement was observed in both groups. The craniofacial osteolysis of GSD showed diffuse involvement with clinical symptoms, whereas that of GLA showed multifocal involvement without clinical symptoms. (orig.)

  3. Carcino-Embryonic Antigen

    International Nuclear Information System (INIS)

    Akute, O.

    1999-02-01

    Tumour marker analysis has increased our understanding of the presence of tumours in the body. Carcino-embryonic antigen, CEA, is one of the best studied tumour markers and has proved an ideal diagnostic adjuvant. It has helped in quantifying the amount of disease present in a patient and thence to make accurate prognosis on the various diagnosed ailments. At UCH, it is observed that there is an increase in cancer related ailments and therefore the need for early diagnosis is more compelling in our environment to mitigate future cost of managing advanced manifestation

  4. Endothelial-Mesenchymal Transition in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Damian Medici

    2016-01-01

    Full Text Available Endothelial-mesenchymal transition (EndMT is a fundamental cellular mechanism that regulates embryonic development and diseases such as cancer and fibrosis. Recent developments in biomedical research have shown remarkable potential to harness the EndMT process for tissue engineering and regeneration. As an alternative to traditional or artificial stem cell therapies, EndMT may represent a safe method for engineering new tissues to treat degenerative diseases by mimicking a process that occurs in nature. This review discusses the signaling mechanisms and therapeutic inhibitors of EndMT, as well as the role of EndMT in development, disease, acquiring stem cell properties and generating connective tissues, and its potential as a novel mechanism for tissue regeneration.

  5. Coordinate Systems Integration for Craniofacial Database from Multimodal Devices

    Directory of Open Access Journals (Sweden)

    Deni Suwardhi

    2005-05-01

    Full Text Available This study presents a data registration method for craniofacial spatial data of different modalities. The data consists of three dimensional (3D vector and raster data models. The data is stored in object relational database. The data capture devices are Laser scanner, CT (Computed Tomography scan and CR (Close Range Photogrammetry. The objective of the registration is to transform the data from various coordinate systems into a single 3-D Cartesian coordinate system. The standard error of the registration obtained from multimodal imaging devices using 3D affine transformation is in the ranged of 1-2 mm. This study is a step forward for storing the craniofacial spatial data in one reference system in database.

  6. An unusual complication after craniofacial surgery for Apert syndrome

    Directory of Open Access Journals (Sweden)

    Abhay A Lune

    2014-01-01

    A case of Apert syndrome who had undergone craniofacial surgery elsewhere 4 years back presented to us with purulent discharge near the lateral orbital margin of right orbit, watering and redness of the right eye. He had telltale signs of this syndrome in the form of skull deformities such as brachycephaly, frontal bony prominence, mid-face hypoplasia, proptosis and syndactyly of both hands and feet. There was a surgical scar of previous craniofacial surgery over the bi-coronal region. He had a discharging granuloma over the lateral orbital margin and the adjacent lower eyelid had developed cicatricial ectropion. X-ray and computed tomography scan orbit confirmed the clinical suspicion of osteomyelitis of the underlying zygomatic bone at the site of miniplate and screw fixation of the earlier surgery. He was treated with excision of granuloma and extraction of loose screw and infected miniplate while ectropion was corrected by rotation advancement of temporal skin flap.

  7. Craniofacial and pharyngeal airway morphology in patients with acromegaly.

    Science.gov (United States)

    Balos Tuncer, Burcu; Canigur Bavbek, Nehir; Ozkan, Cigdem; Tuncer, Cumhur; Eroglu Altinova, Alev; Gungor, Kahraman; Akturk, Mujde; Balos Toruner, Fusun

    2015-08-01

    The aim of this study was to assess differences in craniofacial characteristics, upper spine and pharyngeal airway morphology in patients with acromegaly compared with healthy individuals. Twenty-one patients with acromegaly were compared with 22 controls by linear and angular measurements on cephalograms. The differences between the mean values of cephalometric parameters were analyzed with Mann-Whitney U-test. With respect to controls, anterior (pacromegaly. Craniofacial changes were predominantly found in the frontal bone (pacromegaly exhibited diminished dimensions at nasal (pacromegaly. Current results point to the importance of the reduced airway dimensions and that dentists and/or orthodontists should be aware of the cranial or dental abnormalities in patients with acromegaly.

  8. Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development

    Czech Academy of Sciences Publication Activity Database

    Celá, Petra; Hampl, Marek; Shylo, N.; Christopher, K. J.; Kavková, M.; Landová, Marie; Zikmund, T.; Weatherbee, S. D.; Kaiser, J.; Buchtová, Marcela

    2018-01-01

    Roč. 97, č. 1 (2018), s. 108-117 ISSN 0022-0345 R&D Projects: GA ČR(CZ) GB14-37368G; GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 Keywords : craniofacial anomalies * growth/development * mineralized tissue/development * orofacial clefts * cell signaling Subject RIV: EA - Cell Biology Impact factor: 4.755, year: 2016

  9. Redundant roles of PRDM family members in zebrafish craniofacial development.

    Science.gov (United States)

    Ding, Hai-Lei; Clouthier, David E; Artinger, Kristin B

    2013-01-01

    PRDM proteins are evolutionary conserved Zn-Finger transcription factors that share a characteristic protein domain organization. Previous studies have shown that prdm1a is required for the specification and differentiation of neural crest cells in the zebrafish. Here we examine other members of this family, specifically prdm3, 5, and 16, in the differentiation of the zebrafish craniofacial skeleton. prdm3 and prdm16 are strongly expressed in the pharyngeal arches, while prdm5 is expressed specifically in the area of the forming neurocranium. Knockdown of prdm3 and prdm16 results in a reduction in the neural crest markers dlx2a and barx1 and defects in both the viscerocranium and the neurocranium. The knockdown of prdm3 and prdm16 in combination is additive in the neurocranium, but not in the viscerocranium. Injection of sub-optimal doses of prdm1a with prdm3 or prdm16 Morpholinos together leads to more severe phenotypes in the viscerocranium and neurocranium. prdm5 mutants have defects in the neurocranium and prdm1a and prdm5 double mutants also show more severe phenotypes. Overall, our data reveal that prdm3, 5, and 16 are involved in the zebrafish craniofacial development and that prdm1a may interact with prdm3, 5, and 16 in the formation of the craniofacial skeleton in zebrafish. Copyright © 2012 Wiley Periodicals, Inc.

  10. Advances in imaging: impact on studying craniofacial bone structure.

    Science.gov (United States)

    Majumdar, S

    2003-01-01

    Methods for measuring the structure of craniofacial bones are discussed in this paper. In addition to the three-dimensional macro-structure of the craniofacial skeleton, there is considerable interest in imaging the bone at a microscopic resolution in order to depict the micro-architecture of the trabecular bone itself. In addition to the density of the bone, the microarchitecture reflects bone quality. An understanding of bone quality and density changes has implications for a number of craniofacial pathologies, as well as for implant design and understanding the biomechanical function and loading of the jaw. Trabecular bone micro-architecture has been recently imaged using imaging methods such as micro-computed tomography, magnetic resonance imaging, and the images have been used in finite element models to assess bone mechanical properties. In this paper, some of the recent advances in micro-computed tomography and magnetic resonance imaging are reviewed, and their potential for imaging the trabecular bone in mandibular bones is presented. Examples of in vitro and in vivo images are presented.

  11. MSX-1 gene expression and regulation in embryonic palatal tissue.

    Science.gov (United States)

    Nugent, P; Greene, R M

    1998-01-01

    The palatal cleft seen in Msx-1 knock-out mice suggests a role for this gene in normal palate development. The cleft is presumed secondary to tooth and jaw malformations, since in situ hybridization suggests that Msx-1 mRNA is not highly expressed in developing palatal tissue. In this study we demonstrate, by Northern blot analysis, the expression of Msx-1, but not Msx-2, in the developing palate and in primary cultures of murine embryonic palate mesenchymal cells. Furthermore, we propose a role for Msx-1 in retinoic acid-induced cleft palate, since retinoic acid inhibits Msx-1 mRNA expression in palate mesenchymal cells. We also demonstrate that transforming growth factor beta inhibits Msx-1 mRNA expression in palate mesenchymal cells, with retinoic acid and transforming growth factor beta acting synergistically when added simultaneously to these cells. These data suggest a mechanistic interaction between retinoic acid, transforming growth factor beta, and Msx-1 in the etiology of retinoic acid-induced cleft palate.

  12. Anteverted internal auditory canal as an inner ear anomaly in patients with craniofacial microsomia.

    Science.gov (United States)

    L'Heureux-Lebeau, Bénédicte; Saliba, Issam

    2014-09-01

    Craniofacial microsomia involves structure of the first and second branchial arches. A wide range of ear anomalies, affecting external, middle and inner ear, has been described in association with this condition. We report three cases of anteverted internal auditory canal in patients presenting craniofacial microsomia. This unique internal auditory canal orientation was found on high-resolution computed tomography of the temporal bones. This internal auditory canal anomaly is yet unreported in craniofacial anomalies. Copyright © 2014. Published by Elsevier Ireland Ltd.

  13. 3D craniofacial registration using thin-plate spline transform and cylindrical surface projection.

    Science.gov (United States)

    Chen, Yucong; Zhao, Junli; Deng, Qingqiong; Duan, Fuqing

    2017-01-01

    Craniofacial registration is used to establish the point-to-point correspondence in a unified coordinate system among human craniofacial models. It is the foundation of craniofacial reconstruction and other craniofacial statistical analysis research. In this paper, a non-rigid 3D craniofacial registration method using thin-plate spline transform and cylindrical surface projection is proposed. First, the gradient descent optimization is utilized to improve a cylindrical surface fitting (CSF) for the reference craniofacial model. Second, the thin-plate spline transform (TPST) is applied to deform a target craniofacial model to the reference model. Finally, the cylindrical surface projection (CSP) is used to derive the point correspondence between the reference and deformed target models. To accelerate the procedure, the iterative closest point ICP algorithm is used to obtain a rough correspondence, which can provide a possible intersection area of the CSP. Finally, the inverse TPST is used to map the obtained corresponding points from the deformed target craniofacial model to the original model, and it can be realized directly by the correspondence between the original target model and the deformed target model. Three types of registration, namely, reflexive, involutive and transitive registration, are carried out to verify the effectiveness of the proposed craniofacial registration algorithm. Comparison with the methods in the literature shows that the proposed method is more accurate.

  14. 3D craniofacial registration using thin-plate spline transform and cylindrical surface projection.

    Directory of Open Access Journals (Sweden)

    Yucong Chen

    Full Text Available Craniofacial registration is used to establish the point-to-point correspondence in a unified coordinate system among human craniofacial models. It is the foundation of craniofacial reconstruction and other craniofacial statistical analysis research. In this paper, a non-rigid 3D craniofacial registration method using thin-plate spline transform and cylindrical surface projection is proposed. First, the gradient descent optimization is utilized to improve a cylindrical surface fitting (CSF for the reference craniofacial model. Second, the thin-plate spline transform (TPST is applied to deform a target craniofacial model to the reference model. Finally, the cylindrical surface projection (CSP is used to derive the point correspondence between the reference and deformed target models. To accelerate the procedure, the iterative closest point ICP algorithm is used to obtain a rough correspondence, which can provide a possible intersection area of the CSP. Finally, the inverse TPST is used to map the obtained corresponding points from the deformed target craniofacial model to the original model, and it can be realized directly by the correspondence between the original target model and the deformed target model. Three types of registration, namely, reflexive, involutive and transitive registration, are carried out to verify the effectiveness of the proposed craniofacial registration algorithm. Comparison with the methods in the literature shows that the proposed method is more accurate.

  15. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    Science.gov (United States)

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  16. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  17. Adipose-derived mesenchymal stem cells and regenerative medicine.

    Science.gov (United States)

    Konno, Masamitsu; Hamabe, Atsushi; Hasegawa, Shinichiro; Ogawa, Hisataka; Fukusumi, Takahito; Nishikawa, Shimpei; Ohta, Katsuya; Kano, Yoshihiro; Ozaki, Miyuki; Noguchi, Yuko; Sakai, Daisuke; Kudoh, Toshihiro; Kawamoto, Koichi; Eguchi, Hidetoshi; Satoh, Taroh; Tanemura, Masahiro; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2013-04-01

    Adipose tissue-derived mesenchymal stem cells (ADSCs) are multipotent and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Compared with the extraction of other stem cells such as bone marrow-derived mesenchymal stem cells (BMSCs), that of ADSCs requires minimally invasive techniques. In the field of regenerative medicine, the use of autologous cells is preferable to embryonic stem cells or induced pluripotent stem cells. Therefore, ADSCs are a useful resource for drug screening and regenerative medicine. Here we present the methods and mechanisms underlying the induction of multilineage cells from ADSCs. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  18. Epithelial-mesenchymal transition: Understanding the basic concept

    Directory of Open Access Journals (Sweden)

    Suresh Babu Ghanta

    2012-01-01

    Full Text Available The epithelial-mesenchymal transition (EMT is described as a rapid and reversible process of change of cell phenotype seen during embryonic development, organ fibrosis, and tumor progression. EMT was first described by Gary Greenberg and Elizabeth Hay in 1982. During EMT the epithelial cells alter their cell polarity, reorganize their cytoskeleton thus become isolated and motile. Depending upon the biological context in which they occur, EMT is divided into three types namely EMT type I, II, III. The article describes the process of EMT implicated in the oral cavity as in palate and root development (type I EMT, gingival fibromatosis and oral sub-mucous fibrosis (type II EMT, and oral squamous cell carcinoma (type III EMT. The reverse process of EMT is called as mesenchymal-epithelial transition seen in association with kidney formation.

  19. Epithelial–Mesenchymal Transitions during Neural Crest and Somite Development

    Directory of Open Access Journals (Sweden)

    Chaya Kalcheim

    2015-12-01

    Full Text Available Epithelial-to-mesenchymal transition (EMT is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and vice-versa are intimately associated with the segregation of homogeneous precursors into distinct fates. The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes. Ongoing studies progressively elucidate the gene networks underlying EMT in each system, highlighting the similarities and differences between them. Knowledge of the mechanistic logic of this normal ontogenetic process should provide important insights to the understanding of pathological conditions such as cancer metastasis, which shares some common molecular themes.

  20. Transcriptional profiling of the human fibrillin/LTBP gene family, key regulators of mesenchymal cell functions

    DEFF Research Database (Denmark)

    Davis, Margaret R.; Andersson, Robin; Severin, Jessica

    2014-01-01

    in the structure of the extracellular matrix and controlling the bioavailability of TGFβ family members. Genes encoding these proteins show differential expression in mesenchymal cell types which synthesize the extracellular matrix. We have investigated the promoter regions of the seven gene family members using...... of the family members were expressed in a range of mesenchymal and other cell types, often associated with use of alternative promoters or transcription start sites within a promoter in different cell types. FBN3 was the lowest expressed gene, and was found only in embryonic and fetal tissues. The different...

  1. Epithelial-mesenchymal Transition---A Hallmark of Breast Cancer Metastasis.

    Science.gov (United States)

    Wang, Yifan; Zhou, Binhua P

    2013-03-01

    Epithelial-mesenchymal transition (EMT) is a highly conserved cellular program that converts polarized, immotile epithelial cells to migratory mesenchymal cells. In addition, EMT was initially recognized as a key step for morphogenesis during embryonic development. Emerging evidences indicate that this important developmental program promotes metastasis, drug resistance, and tumor recurrence, features that are associated with a poor clinical outcome for patients with breast cancer. Therefore, better understanding of regulation and signaling pathways in EMT is essential to develop novel targeted therapeutics. In this review, we present updated developments underlying EMT in tumor progression and metastasis, and discuss the challenges remaining in breast cancer research.

  2. Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Kaori [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Taketomi, Takaharu, E-mail: taketomi@dent.kyushu-u.ac.jp [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshizaki, Keigo [Section of Orthodontics, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Arai, Shinsaku [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sanui, Terukazu [Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshiga, Daigo [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshimura, Akihiko [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo 102-0075 (Japan); Nakamura, Seiji [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2011-01-28

    Research highlights: {yields} Sprouty2-deficient mice exhibit cleft palate as a result of failure of palatal shelf elevation. {yields} We examined palate cell proliferation in Sprouty2-deficient mice. {yields} Palate mesenchymal cell proliferation was increased in Sprouty2 KO mice. {yields} Sprouty2 plays roles in murine palatogenesis by regulating cell proliferation. -- Abstract: Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.

  3. Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

    International Nuclear Information System (INIS)

    Matsumura, Kaori; Taketomi, Takaharu; Yoshizaki, Keigo; Arai, Shinsaku; Sanui, Terukazu; Yoshiga, Daigo; Yoshimura, Akihiko; Nakamura, Seiji

    2011-01-01

    Research highlights: → Sprouty2-deficient mice exhibit cleft palate as a result of failure of palatal shelf elevation. → We examined palate cell proliferation in Sprouty2-deficient mice. → Palate mesenchymal cell proliferation was increased in Sprouty2 KO mice. → Sprouty2 plays roles in murine palatogenesis by regulating cell proliferation. -- Abstract: Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.

  4. Embryonic duplications in sheep.

    Science.gov (United States)

    Dennis, S M

    1975-02-01

    Twenty-seven embryonic duplications were examined during a 3-year investigation into the causes of perinatal lamb mortality. Twenty of the 27 were anomalous twins with 19 being conjoined (diplopagus 9 and heteropagus 10). The various duplications were: haloacardius acephalus 1, diprosopus 2, dicephalus 2, dipypus 3, diprosopus dipygus 1, syncephalus dipygus 1, pygopagus parasiticus 1, heteropagus dipygus 3, melodidymus 6, polyury 4, penile duplication 2, and bilateral otognathia 1. Four lambs were living and the time of death of the others was: parturient 8, and post-parturient 15. Average dry weight of the lambs was 3.35 kg (range 1.59 to 5.45 kg). Breed distribution was: Merino 77.8%, Crossbred 14.8%, Dorset Horn 3.7%, and Corriedale 3.7%. The caudal region was involved in 10 of the conjoined twins (52.6%), anterior region in 7 (36.9%), and both anterior and caudal regions in 2 (10.5%). Associated defects were present in 70.4% of the 27 lambs, the most common being atresia ani.

  5. Magnesium Alloys as a Biomaterial for Degradable Craniofacial Screws

    Science.gov (United States)

    Henderson, Sarah E.; Verdelis, Konstantinos; Maiti, Spandan; Pal, Siladitya; Chung, William L.; Chou, Da-Tren; Kumta, Prashant N.; Almarza, Alejandro J.

    2014-01-01

    Recently, magnesium (Mg) alloys have received significant attention as a potential biomaterial for degradable implants, and this study was directed at evaluating the suitability of Mg for craniofacial bone screws. The objective was to implant screws fabricated from commercially available Mg-alloys (pure Mg and AZ31) in-vivo in a rabbit mandible. First, Mg-alloy screws were compared to stainless steel screws in an in-vitro pull-out test and determined to have a similar holding strength (~40N). A finite element model of the screw was created using the pull-out test data, and the model can be used for future Mg-alloy screw design. Then, Mg-alloy screws were implanted for 4, 8, and 12 weeks, with two controls of an osteotomy site (hole) with no implant and a stainless steel screw implanted for 12 weeks. MicroCT (computed tomography) was used to assess bone remodeling and Mg-alloy degradation, both visually and qualitatively through volume fraction measurements for all time points. Histologic analysis was also completed for the Mg-alloys at 12 weeks. The results showed that craniofacial bone remodeling occurred around both Mg-alloy screw types. Pure Mg had a different degradation profile than AZ31, however bone growth occurred around both screw types. The degradation rate of both Mg-alloy screw types in the bone marrow space and the muscle were faster than in the cortical bone space at 12 weeks. Furthermore, it was shown that by alloying Mg, the degradation profile could be changed. These results indicate the promise of using Mg-alloys for craniofacial applications. PMID:24384125

  6. 75 FR 82033 - National Institute of Dental and Craniofacial Research; Notice of Meeting

    Science.gov (United States)

    2010-12-29

    ... and Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory... 31C, 31 Center Drive, 6th Floor, Conference Room 10, Bethesda, MD 20892. Contact Person: Alicia J. Dombroski, PhD, Director, Division of Extramural Activities, Natl. Inst. of Dental and Craniofacial Research...

  7. 76 FR 51995 - National Institute of Dental & Craniofacial Research; Notice of Meeting

    Science.gov (United States)

    2011-08-19

    ... & Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... 31 C, 31 Center Drive, 6th Floor, Conference Room 10, Bethesda, MD 20892. Contact Person: Alicia J. Dombroski, PhD, Director, Division of Extramural Activities, National Institute of Dental and Craniofacial...

  8. A stereotactic system for guiding complex craniofacial reconstruction.

    Science.gov (United States)

    Fialkov, J A; Phillips, J H; Gruss, J S; Kassel, E E; Zuker, R M

    1992-02-01

    A stereotactic system has been designed to address the problem of achieving symmetry in complex and extensive craniofacial defects. Preliminary testing suggests that such a system, which allows for the intraoperative application of preoperative CT planning, will be useful in guiding the reconstruction of congenital or acquired bony time, is being used to investigate the correlation of intraoperative globe position following enophthalmos correction with long-term outcome, particularly as it relates to the size and location of the orbital defect, and the timing of the procedure.

  9. Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

    Science.gov (United States)

    Dechow, Paul C.; Wang, Qian; Peterson, Jill

    2011-01-01

    Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which

  10. Operative correction and follow-up of craniofacial duplication.

    Science.gov (United States)

    Kotrikova, Bibiana; Hassfeld, Stefan; Steiner, Hans H; Hähnel, Stefan; Krempien, Robert; Mühling, Joachim

    2007-03-01

    Anterior craniofacial duplication (diprosopus) is an extremely rare form of conjoined twins. The children share a single trunk with normal extremities and varying degrees of facial malformation. Duplication of specific structures, such as the nose (diprosopus dirrhinus), eyes (diprosopus tetraophthalmus), and ears, is possible. The authors present a case of partial facial duplication (diprosopus dirrhinus) in a male infant. The clinical and radiographic findings and the surgical correction and follow-up are described. In a single surgical session, the authors were able to achieve not only a functionally but also an aesthetically acceptable result. In the postoperative course, the child showed nearly normal growth and satisfactory psychosocial and motor development. However, 40 months postoperatively, we noticed a tendency of the orbitae to diverge (i.e., toward hypertelorism). The surgical management of complex craniofacial malformations such as diprosopus needs a precise morphologic analysis of the patient's deformity followed by a clear treatment plan. A staged reconstructive approach is carried out to coincide with facial growth patterns and brain and eye function. If the interorbital distance in our patient increases progressively, a second operation for reduction of the interorbital distance may be necessary.

  11. Craniofacial resection in nasal cavity and paranasal sinus carcinoma

    International Nuclear Information System (INIS)

    Arias Garzon, Williams Rene; Cohn, Fabrizio; Toscano Mancheno, Roberto; Chonlong Saltos, Maria Jose

    2006-01-01

    The nasal cavity and paranasal sinus carcinoma include 1% of all malignant tumors and 3% in head and neck region. The majority of tumors of this region are squamous cell carcinomas, which rises in the maxillary sinus and generates symptoms when it reaches a great size. Treatment is very difficult. The Cat scan and magnetic resonance are helpful to evaluate the tumor extent, asses erode bone boundary and evaluate growth in soft tissues of intra skull like the dura overlying the frontal lobe and brain. The growth of the tumor in the anterior skull base is not a contraindication for surgical treatment. A combined intracranial facial approach to the paranasal sinuses carcinoma enables complete tumor resection and edges without neoplasm. The 5 year survival for patients who undergo anterior craniofacial resection is approximately 50 to 60%, and local tumor control is obtained in 65%. We present a patient with squamous carcinoma of superior maxillary antrum and skull base encroachment invasion resolved with craniofacial resection. (The author)

  12. Craniofacial Surgery and Adverse Outcomes: An Inquiry Into Medical Negligence.

    Science.gov (United States)

    Svider, Peter F; Eloy, Jean Anderson; Folbe, Adam J; Carron, Michael A; Zuliani, Giancarlo F; Shkoukani, Mahdi A

    2015-07-01

    This study aimed to evaluate factors contributing to medical negligence relevant to craniofacial surgery. Retrospective analysis of verdict and settlement reports on the Westlaw legal database for outcome, awards, physician defendants, and other specific factors raised in malpractice litigation. Of 42 verdicts and settlement reports included, 52.4% were resolved with either an out-of-court settlement or plaintiff verdict, with aggregate payments totaling $50.1M (in 2013 dollars). Median settlements and jury-awarded damages were $988,000 and $555,000, respectively. Payments in pediatric cases ($1.2M) were significantly higher. Plastic surgeons, oral surgeons, and otolaryngologists were the most commonly named defendants. The most common alleged factors included intraoperative negligence (69.0%), permanent deficits (54.8%), requiring additional surgery (52.4%), missed/delayed diagnosis of a complication (42.9%), disfigurement/scarring (28.6%), postoperative negligence (28.6%), and inadequate informed consent (20.6% of surgical cases). Failure to diagnose a fracture (19.0%) and cleft-reparative procedures (14.3%) were the most frequently litigated entities. Medical negligence related to craniofacial surgery involves plaintiffs in a wide age range as well as physician defendants in numerous specialties, and proceedings resolved with settlement and plaintiff verdict involve substantial payments. Cases with death, allegedly permanent injuries, and pediatric plaintiffs had significantly higher payments. © The Author(s) 2015.

  13. Creation of three-dimensional craniofacial standards from CBCT images

    Science.gov (United States)

    Subramanyan, Krishna; Palomo, Martin; Hans, Mark

    2006-03-01

    Low-dose three-dimensional Cone Beam Computed Tomography (CBCT) is becoming increasingly popular in the clinical practice of dental medicine. Two-dimensional Bolton Standards of dentofacial development are routinely used to identify deviations from normal craniofacial anatomy. With the advent of CBCT three dimensional imaging, we propose a set of methods to extend these 2D Bolton Standards to anatomically correct surface based 3D standards to allow analysis of morphometric changes seen in craniofacial complex. To create 3D surface standards, we have implemented series of steps. 1) Converting bi-plane 2D tracings into set of splines 2) Converting the 2D splines curves from bi-plane projection into 3D space curves 3) Creating labeled template of facial and skeletal shapes and 4) Creating 3D average surface Bolton standards. We have used datasets from patients scanned with Hitachi MercuRay CBCT scanner providing high resolution and isotropic CT volume images, digitized Bolton Standards from age 3 to 18 years of lateral and frontal male, female and average tracings and converted them into facial and skeletal 3D space curves. This new 3D standard will help in assessing shape variations due to aging in young population and provide reference to correct facial anomalies in dental medicine.

  14. Embryonal rhabdomyosarcoma in an immature Baird's tapir (Tapirus bairdii).

    Science.gov (United States)

    Bonar, Christopher J; Lewandowski, Albert H; Skowronek, Anthony J

    2007-03-01

    An immature Baird's tapir (Tapirus bairdii) with a history of seizure-like episodes developed signs of respiratory disease. The initial clinical diagnosis was pneumonia, and antibiotic therapy was started. The animal failed to improve after 14 days of therapy and developed unilateral, bloody nasal discharge. Endoscopic examination and radiography revealed a soft tissue mass in the nasopharynx depressing the soft palate. The tapir died 32 days after initial presentation. Histologic examination of the mass demonstrated a mesenchymal tumor composed of spindle cells with elongate nuclei forming densely packed fascicles. The neoplastic spindle cells showed prominent cross-striations. Immunohistochemistry revealed the cells to be positive for desmin and myoglobin, but negative for smooth muscle actin, confirming diagnosis of rhabdomyosarcoma. Embryonal rhabdomyosarcoma is the most common nasopharyngeal soft tissue tumor of humans, and it has been reported infrequently in dogs, horses, and pigs. Neoplasia should be a differential diagnosis in cases of unilateral nasal discharge and inspiratory stridor, even in young animals.

  15. Mechanobiology of embryonic limb development.

    Science.gov (United States)

    Nowlan, Niamh C; Murphy, Paula; Prendergast, Patrick J

    2007-04-01

    Considerable evidence exists to support the hypothesis that mechanical forces have an essential role in healthy embryonic skeletal development. Clinical observations and experimental data indicate the importance of muscle contractions for limb development. However, the influence of these forces is seldom referred to in biological descriptions of bone development, and perhaps this is due to the fact that the hypothesis that mechanical forces are essential for normal embryonic skeletal development is difficult to test and elaborate experimentally in vivo, particularly in humans. Computational modeling has the potential to address this issue by simulating embryonic growth under a range of loading conditions but the potential of such models has yet to be fully exploited. In this article, we review the literature on mechanobiology of limb development in three main sections: (a) experimental alteration of the mechanical environment, (b) mechanical properties of embryonic tissues, and (c) the use of computational models. Then we analyze the main issues, and suggest how experimental and computational fields could work closer together to enhance our understanding of mechanobiology of the embryonic skeleton.

  16. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  17. Diagnostic imaging of craniofacial trauma and fractures and their sequelae

    International Nuclear Information System (INIS)

    Buitrago-Tellez, C.H.; Kunz, C.

    2001-01-01

    The value and applications of the CT modalities are on the rise, particularly since the availability of spiral CT techniques, while conventional native diagnostics is increasingly used for special imaging purposes. Multiplanar spiral CT enables high-quality coronary 2D reconstructions which, in the acute phase, make redundant primary coronary imaging modalities. Exact knowledge of typical fracture patterns facilitates the analysis of images of the relevant facial areas. 3D reconstructions are indispensable in pin-pointed surgery planning, generation of stereolithographic models, and image-guided interventions for examination of post-traumatic deformities. Since a secondary correction only very rarely leads to restitutio ad integrum, it is necessary to detect the therapy-relevant injuries very early, during acute diagnostic imaging, in order to lay the basis for subsequent therapy and restoration of the craniofacial structures and functions. (orig./CB) [de

  18. Generation of stomach tissue from mouse embryonic stem cells.

    Science.gov (United States)

    Noguchi, Taka-aki K; Ninomiya, Naoto; Sekine, Mari; Komazaki, Shinji; Wang, Pi-Chao; Asashima, Makoto; Kurisaki, Akira

    2015-08-01

    Successful pluripotent stem cell differentiation methods have been developed for several endoderm-derived cells, including hepatocytes, β-cells and intestinal cells. However, stomach lineage commitment from pluripotent stem cells has remained a challenge, and only antrum specification has been demonstrated. We established a method for stomach differentiation from embryonic stem cells by inducing mesenchymal Barx1, an essential gene for in vivo stomach specification from gut endoderm. Barx1-inducing culture conditions generated stomach primordium-like spheroids, which differentiated into mature stomach tissue cells in both the corpus and antrum by three-dimensional culture. This embryonic stem cell-derived stomach tissue (e-ST) shared a similar gene expression profile with adult stomach, and secreted pepsinogen as well as gastric acid. Furthermore, TGFA overexpression in e-ST caused hypertrophic mucus and gastric anacidity, which mimicked Ménétrier disease in vitro. Thus, in vitro stomach tissue derived from pluripotent stem cells mimics in vivo development and can be used for stomach disease models.

  19. Sella turcica-Its importance in orthodontics and craniofacial morphology

    Directory of Open Access Journals (Sweden)

    Haritha Pottipalli Sathyanarayana

    2013-01-01

    Full Text Available The sella turcica is a structure which can be readily seen on lateral cephalometric radiographs and sella point is routinely traced for various cephalometric analyses. The search was carried out using the following key words (sella turcica, bridging of sella, size, shape of sella turcica and with the following search engine (Pubmed, Cochrane, Google scholar. The morphology is very important for the cephalometric position of the reference point sella, not only for evaluating craniofacial morphology, but also when growth changes and orthodontic treatment results are to be evaluated. This makes it a good source of additional diagnostic information related to pathology of the pituitary gland, or to various syndromes that affect the craniofacial region. Clinicians should be familiar with the normal radiographic anatomy and morphologic variability of this area, in order to recognize and investigate deviations that may reflect pathological situations, even before these become clinically apparent. During embryological development, the sella turcica area is the key point for the migration of the neural crest cells to the frontonasal and maxillary developmental fields. The neural crest cells are involved in the formation and development of sella turcica and teeth. The size of sella turcica ranges from 4 to 12 mm for the vertical and 5 to 16 mm for the anteroposterior dimension. There are many classification systems regarding the shape of sella turcica. Majority of the studies show that about 67% of the subjects had normal appearance and about 33% showed variations. The prevalence of sella turcica bridging is high in class III malocclusions and dental anomalies.

  20. MORN5 expression during craniofacial development and its interaction with the BMP and TGFB pathways

    Directory of Open Access Journals (Sweden)

    Petra Cela

    2016-08-01

    Full Text Available MORN5 (MORN repeat containing 5 is encoded by a locus positioned on chromosome 17 in the chicken genome. The MORN motif is found in multiple copies in several proteins including junctophilins or phosphatidylinositol phosphate kinase family and the MORN proteins themselves are found across the animal and plant kingdoms. MORN5 protein has a characteristic punctate pattern in the cytoplasm in immunofluorescence imaging. Previously, MORN5 was found among differentially expressed genes in a microarray profiling experiment of the chicken embryo head. Here, we provided in situ hybridization to analyse, in detail, the MORN5 expression in chick craniofacial structures. The expression of MORN5 was first observed at stage HH17-18 (E2.5. MORN5 expression gradually appeared on either side of the primitive oral cavity, within the maxillary region. At stage HH20 (E3, prominent expression was localised in the mandibular prominences lateral to the midline. From stage HH20 up to HH29 (E6, there was strong expression in restricted regions of the maxillary and mandibular prominences. The frontonasal mass (in the midline of the face expresses MORN5, starting at HH27 (E5. The expression was concentrated in the corners or globular processes, which will ultimately fuse with the cranial edges of the maxillary prominences. MORN5 expression was maintained in the fusion zone up to stage HH29. In sections in situs, MORN5 expression was localised preferentially in the mesenchyme. We examined signals that regulate MORN5 expression in the face based on a previous microarray study. Here we validated the array results with in situ hybridization and QPCR. MORN5 was downregulated 24h after Noggin and/or RA treatment. We also determined that BMP pathway genes are downstream of MORN5 following siRNA knockdown. Based on these results, we conclude that MORN5 is both regulated by and required for BMP signalling. The restricted expression of MORN5 in the lip fusion zone shown here

  1. Tissue engineered bone versus alloplastic commercial biomaterials in craniofacial reconstruction.

    Science.gov (United States)

    Lucaciu, Ondine; Băciuţ, Mihaela; Băciuţ, G; Câmpian, R; Soriţău, Olga; Bran, S; Crişan, B; Crişan, Liana

    2010-01-01

    This research was developed in order to demonstrate the tissue engineering method as an alternative to conventional methods for bone reconstruction, in order to overcome the frequent failures of alloplastic commercial biomaterials, allografts and autografts. Tissue engineering is an in vitro method used to obtain cell based osteoinductive bone grafts. This study evaluated the feasibility of creating tissue-engineered bone using mesenchymal cells seeded on a scaffold obtained from the deciduous red deer antler. We have chosen mesenchymal stem cells because they are easy to obtain, capable to differentiate into cells of mesenchymal origin (osteoblasts) and to produce tissue such as bone. As scaffold, we have chosen the red deer antler because it has a high level of porosity. We conducted a case control study, on three groups of mice type CD1--two study groups (n=20) and a control group (n=20). For the study groups, we obtained bone grafts through tissue engineering, using mesenchymal stem cells seeded on the scaffold made of deciduous red deer antler. Bone defects were surgically induced on the left parietal bone of all subjects. In the control group, we grafted the bone defects with commercial biomaterials (OsteoSet, Wright Medical Technology, Inc., Arlington, Federal USA). Subjects were sacrificed at two and four months, the healing process was morphologically and histologically evaluated using descriptive histology and the golden standard - histological scoring. The grafts obtained in vivo through tissue engineering using adult stem cell, seeded on the scaffold obtained from the red deer antler using osteogenic medium have proven their osteogenic properties.

  2. Craniofacial duplication (diprosopus): report of a case with a review of the literature.

    Science.gov (United States)

    Amr, S S; Hammouri, M F

    1995-01-01

    A case of craniofacial duplication (diprosopus) is presented. Details on this rare form of conjoined twins are described, and the proposed theories of its embryogenesis are discussed with brief review of the pertinent literature.

  3. 77 FR 35990 - National Institute of Dental and Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-15

    ... Craniofacial Research Special Emphasis Panel; Molecular Characterization of Salivary Tumors RFA: R01 and R21...: Jayalakshmi Raman, Ph.D., Scientific Review Officer, Scientific Review Branch, National Institute of Dental...

  4. Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas

    NARCIS (Netherlands)

    Wensman, H.; Goransson, H.; Leuchowius, K.J.; Stromberg, S.; Ponten, F.; Isaksson, A.; Rutteman, G.R.; Heldin, N.; Pejler, G.; Hellmen, E.

    2009-01-01

    Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas Journal Breast Cancer Research and Treatment Publisher Springer Netherlands ISSN 0167-6806 (Print) 1573-7217 (Online) Issue Volume 118, Number 2 / November, 2009 Category Preclinical Study DOI

  5. Removal of symptomatic craniofacial titanium hardware following craniotomy: Case series and review

    Directory of Open Access Journals (Sweden)

    Sheri K. Palejwala

    2015-06-01

    Full Text Available Titanium craniofacial hardware has become commonplace for reconstruction and bone flap fixation following craniotomy. Complications of titanium hardware include palpability, visibility, infection, exposure, pain, and hardware malfunction, which can necessitate hardware removal. We describe three patients who underwent craniofacial reconstruction following craniotomies for trauma with post-operative courses complicated by medically intractable facial pain. All three patients subsequently underwent removal of the symptomatic craniofacial titanium hardware and experienced rapid resolution of their painful parasthesias. Symptomatic plates were found in the region of the frontozygomatic suture or MacCarty keyhole, or in close proximity with the supraorbital nerve. Titanium plates, though relatively safe and low profile, can cause local nerve irritation or neuropathy. Surgeons should be cognizant of the potential complications of titanium craniofacial hardware and locations that are at higher risk for becoming symptomatic necessitating a second surgery for removal.

  6. The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival.

    Science.gov (United States)

    Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J

    2016-08-03

    Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog ( Shh ), a vertebrate orthologue of Drosophila hedgehog , is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible).

  7. The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival

    Directory of Open Access Journals (Sweden)

    Sebastian Dworkin

    2016-08-01

    Full Text Available Craniofacial defects (CFD are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog (Shh, a vertebrate orthologue of Drosophila hedgehog, is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla and lower jaw (mandible.

  8. 78 FR 45934 - The National Institute of Dental and Craniofacial Research (NIDCR) Strategic Plan Request for...

    Science.gov (United States)

    2013-07-30

    ... diseases and disorders, has a distinguished record of supporting research to advance the oral health of the... revolutionizing how we understand, prevent, diagnose and manage dental, oral, and craniofacial diseases and...

  9. Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.

    Science.gov (United States)

    Occhetta, Paola; Pigeot, Sebastien; Rasponi, Marco; Dasen, Boris; Mehrkens, Arne; Ullrich, Thomas; Kramer, Ina; Guth-Gundel, Sabine; Barbero, Andrea; Martin, Ivan

    2018-05-01

    It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.

  10. Partial craniofacial duplication: a review of the literature and case report.

    Science.gov (United States)

    Costa, Melinda A; Borzabadi-Farahani, Ali; Lara-Sanchez, Pedro A; Schweitzer, Daniela; Jacobson, Lia; Clarke, Noreen; Hammoudeh, Jeffery; Urata, Mark M; Magee, William P

    2014-06-01

    Diprosopus (Greek; di-, "two" + prosopon, "face"), or craniofacial duplication, is a rare craniofacial anomaly referring to the complete duplication of facial structures. Partial craniofacial duplication describes a broad spectrum of congenital anomalies, including duplications of the oral cavity. This paper describes a 15 month-old female with a duplicated oral cavity, mandible, and maxilla. A Tessier type 7 cleft, midline meningocele, and duplicated hypophysis were also present. The preoperative evaluation, surgical approach, postoperative results, and a review of the literature are presented. The surgical approach was designed to preserve facial nerve innervation to the reconstructed cheek and mouth. The duplicated mandible and maxilla were excised and the remaining left maxilla was bone grafted. Soft tissue repair included closure of the Tessier type VII cleft. Craniofacial duplication remains a rare entity that is more common in females. The pathophysiology remains incompletely characterized, but is postulated to be due to duplication of the notochord, as well as duplication of mandibular growth centres. While diprosopus is a severe deformity often associated with anencephaly, patients with partial duplication typically benefit from surgical treatment. Managing craniofacial duplication requires a detailed preoperative evaluation as well as a comprehensive, staged treatment plan. Long-term follow up is needed appropriately to address ongoing craniofacial deformity. Published by Elsevier Ltd.

  11. The fusion of craniofacial reconstruction and microsurgery: a functional and aesthetic approach.

    Science.gov (United States)

    Broyles, Justin M; Abt, Nicholas B; Shridharani, Sachin M; Bojovic, Branko; Rodriguez, Eduardo D; Dorafshar, Amir H

    2014-10-01

    Reconstruction of large, composite defects in the craniofacial region has evolved significantly over the past half century. During this time, there have been significant advances in craniofacial and microsurgical surgery. These contributions have often been in parallel; however, over the past 10 years, these two disciplines have begun to overlap more frequently, and the techniques of one have been used to advance the other. In the current review, the authors aim to describe the available options for free tissue reconstruction in craniofacial surgery. A review of microsurgical reconstructive options of aesthetic units within the craniofacial region was undertaken with attention directed toward surgeon flap preference. Anatomical areas analyzed included scalp, calvaria, forehead, frontal sinus, nose, maxilla and midface, periorbita, mandible, lip, and tongue. Although certain flaps such as the ulnar forearm flap and lateral circumflex femoral artery-based flaps were used in multiple reconstructive sites, each anatomical location possesses a unique array of flaps to maximize outcomes. Craniofacial surgery, like plastic surgery, has made tremendous advancements in the past 40 years. With innovations in technology, flap design, and training, microsurgery has become safer, faster, and more commonplace than at any time in history. Reconstructive microsurgery allows the surgeon to be creative in this approach, and free tissue transfer has become a mainstay of modern craniofacial reconstruction.

  12. Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid

    2012-01-01

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth...... and differentiation of hematopoietic stem cells (HSC) and hematopoiesis. These cells have been described as important immunoregulators due to their ability to suppress T cells proliferation. MSC can also directly contribute to tissue repair by migrating to sites of injury and providing a source of cells...... for differentiation and/or providing bystander support for resident stromal cells. This chapter discusses the cellular and molecular properties of MSC, the mechanisms by which they can modulate immune responses and the clinical applications of MSC in disorders such as graft-versus-host disease and aplastic anaemia...

  13. [Gastric mesenchymal tumours (GIST)].

    Science.gov (United States)

    Spivach, Arrigo; Fezzi, Margherita; Sartori, Alberto; Belgrano, Manuel; Rimondini, Alessandra; Cuttin-Zernich, Roberto; Covab, Maria Assunta; Bonifacio, Daniela; Buri, Luigi; Pagani, Carlo; Zanconati, Fabrizio

    2008-01-01

    The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.

  14. Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children

    Energy Technology Data Exchange (ETDEWEB)

    Gabor, Flaviu; Franchi-Abella, Stephanie; Pariente, Daniele [Bicetre Hospital, Department of Pediatric Radiology, Le Kremlin-Bicetre (France); Merli, Laura [Bambino Gesu Children' s Hospital, Unit of Hepato-Biliary and Transplant Surgery, Department of Surgery and Transplantation Centre, Rome (Italy); Adamsbaum, Catherine [Bicetre Hospital, Department of Pediatric Radiology, Le Kremlin-Bicetre (France); Paris Sud University, Faculty of Medicine, Le Kremlin-Bicetre (France); Universite Paris-Saclay, LTCI, CNRS, Telecom Paris Tech, Paris (France)

    2016-11-15

    Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI. (orig.)

  15. Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children

    International Nuclear Information System (INIS)

    Gabor, Flaviu; Franchi-Abella, Stephanie; Pariente, Daniele; Merli, Laura; Adamsbaum, Catherine

    2016-01-01

    Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI. (orig.)

  16. Osterix-Cre transgene causes craniofacial bone development defect

    Science.gov (United States)

    Wang, Li; Mishina, Yuji; Liu, Fei

    2015-01-01

    The Cre/loxP system has been widely used to generate tissue-specific gene knockout mice. Inducible (Tet-off) Osx-GFP::Cre (Osx-Cre) mouse line that targets osteoblasts is widely used in the bone research field. In this study, we investigated the effect of Osx-Cre on craniofacial bone development. We found that newborn Osx-Cre mice showed severe hypomineralization in parietal, frontal, and nasal bones as well as the coronal sutural area when compared to control mice. As the mice matured the intramembranous bone hypomineralization phenotype became less severe. The major hypomineralization defect in parietal, frontal, and nasal bones had mostly disappeared by postnatal day 21, but the defect in sutural areas persisted. Importantly, Doxycycline treatment eliminated cranial bone defects at birth which indicates that Cre expression may be responsible for the phenotype. In addition, we showed that the primary calvarial osteoblasts isolated from neonatal Osx-Cre mice had comparable differentiation ability compared to their littermate controls. This study reinforces the idea that Cre positive litter mates are indispensable controls in studies using conditional gene deletion. PMID:25550101

  17. Craniofacial and maxillary anomalies: Anesthetic implications and management

    Directory of Open Access Journals (Sweden)

    Sukhminder Jit Singh Bajwa

    2014-01-01

    Full Text Available The advancement in the craniofacial surgery has imposed challenges on the attending anesthesiologist for the successful conduct reconstructive surgery. The anesthesiologist remains a key person in the multidisciplinary tasks involved in such surgery. Most of these patients belong to smaller age group and have difficult airway due to various syndromes associated with it. The other major problems faced by the anesthesiologist in such surgery are intra-operative hypothermia due to prolonged surgery and significant blood loss as well as fluid shifts associated with it. A well-equipped intensive care unit is a must for the post-operative care of such patients. Even the adult patients coming for maxillofacial trauma surgery require careful vigilance both intra-operatively as well as post-operatively due to frequent difficult airway associated with it. A careful pre-operative evaluation and discussion with the surgeons, proper planning for airway management, intra-operative care and post-operative intensive care backup is required for the successful outcome in these surgeries. The current review is an attempt to describe in short the important anesthesia aspects and challenges related to various cranio-maxillary lesions.

  18. Opitz C syndrome: Trigonocephaly, mental retardation and craniofacial dysmorphism

    Directory of Open Access Journals (Sweden)

    J.A. Avina Fierro

    2016-01-01

    Full Text Available We describe a 4-year-old female child with a dysmorphic and neurological syndrome of trigonocephaly, mental and psychomotor retardation and dysmorphic facial features. The anomalies of the face were the following: slight upward palpebral fissures, ocular hypertelorism, depressed nasal bridge, hypoplastic nasal root, short nose with anteverted nares; small low set ears, smooth broad philtrum and thin upper lip. The patient had important cerebral anomalies with diffuse alterations in white matter that caused developmental delay with verbal and nonverbal disabilities and severe learning difficulties. This clinical presentation is compatible with the diagnosis of the Opitz C syndrome, a heterogeneous disease of multiple neurological and craniofacial abnormalities. The physical sign more detectable and notorious is the trigonocephaly that is manifested by a prominent metopic suture, but also can be distinguished the other minor facial anomalies that are found in the eyes, nose, mouth and ears that constitute the phenotype of the disorder. The neurological development was altered by the compression of the cerebral frontal lobes with narrowing of this cerebral area, producing hypotonia with muscle weakness, epileptic episodes manifested by seizures, and neurobehavioral and neurocognitive disorders. This syndrome is a very rare genetic disorder with autosomal recessive inheritance trait; our patient had no chromosomal abnormality in the usual karyotype but the fluorescence in situ hybridization (FISH technique showed a balanced translocation between the chromosomes two and eleven: t(2:11 (q32.2/q24.

  19. Characterization of the bending strength of craniofacial sutures.

    Science.gov (United States)

    Maloul, Asmaa; Fialkov, Jeffrey; Whyne, Cari M

    2013-03-15

    The complex, thin and irregular bones of the human craniofacial skeleton (CFS) are connected together through bony articulations and connective tissues. These articulations are known as sutures and are commonly divided into two groups, facial and cranial sutures, based on their location in the CFS. CFS sutures can exhibit highly variable degrees of interdigitation and complexity and are believed to play a role in accommodating the mechanical demands of the skull. This study aimed to evaluate the mechanical behavior of CFS bone samples with and without sutures and to determine the effect of sutural interdigitations on mechanical strength. Sagittal, coronal, frontozygomatic and zygomaticotemporal sutures along with adjacent bone samples not containing sutures were excised from six fresh-frozen cadaveric heads. The interdigitation of the sutures was quantified through μCT based analysis. Three-point bending to failure was performed on a total of 29 samples. The bending strength of bone samples without sutures demonstrated a non-significant increase of 14% as compared to samples containing sutures (P=0.2). The bending strength of bones containing sutures was positively correlated to the sutural interdigitation index (R=0.701, P=0.002). The higher interdigitation indices found in human cranial vs. facial sutures may be present to resist bending loads as a functional requirement in protecting the brain. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Bone markers in craniofacial bone deformations and dysplasias

    Directory of Open Access Journals (Sweden)

    Monika Seifert

    2015-10-01

    Full Text Available Various forms of bony deformations and dysplasias are often present in the facial skeleton. Bone defects can be either localized or general. Quite often they are not only present in the skull but also can be found in other parts of the skeleton. In many cases the presence and levels of specific bone markers should be measured in order to fully describe their activity and presence in the skeleton. Fibrous dysplasia (FD is the most common one in the facial skeleton; however, other bone deformations regarding bone growth and activity can also be present. Every clinician should be aware of all common, rare and uncommon bony diseases and conditions such as cherubism, Paget’s disease, osteogenesis imperfecta and others related to genetic conditions. We present standard (calcium, parathyroid hormone, calcitonin, alkaline phosphatase, vitamin D and specialized bone markers (pyridinium, deoxypyridinium, hydroxyproline, RANKL/RANK/OPG pathway, growth hormone, insulin-like growth hormone-1 that can be used to evaluate, measure or describe the processes occurring in craniofacial bones.

  1. Analysis of an In-Service Examination for Core Pediatric Craniofacial Surgery Knowledge.

    Science.gov (United States)

    Silvestre, Jason; Chang, Benjamin; Taylor, Jesse A

    2016-01-01

    Little is known about designing an effective residency curriculum for pediatric craniofacial surgery. This study elucidates the pediatric craniofacial curriculum of the Plastic Surgery In-Service Training Examination (PSITE) to facilitate knowledge acquisition during residency. Approximately, 6 consecutive PSITEs were reviewed for pediatric craniofacial questions (2010-2015). Subjects were categorized according to topics on the American Board of Plastic Surgery written board examination. Questions were categorized using an educational taxonomy model. Answer references were categorized by source and publication lag. Of 1174 PSITE questions, 147 tested pediatric craniofacial topics (12.5%). Questions appeared predominately in the Craniomaxillofacial section (83.0%, p < 0.001). The annual representation was stable more than 6 years (range: 10.2%-14.4%, p = 0.842). Question taxonomy favored interpretation (45.6%) and decision-making (40.8%) over recall (13.6%, p < 0.001) skills, and 41 questions had an associated image (27.9%) and most were photographic (76.7%, p < 0.001). The most frequently tested categories on the American Board of Plastic Surgery written examination content outline were craniofacial anomalies (23.5%), benign and malignant tumors (17.6%), and cleft lip and palate (12.5%). Overall, 80 unique journals were cited 304 times with a mean publication lag of 9.4 ± 10.9 years. Plastic and Reconstructive Surgery (34.5%) was the most cited journal (p < 0.001). These data may assist in designating core knowledge competency in pediatric craniofacial surgery for plastic surgery residents. A further understanding of PSITE utility for core knowledge competency in pediatric craniofacial surgery would be the focus of future work. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  2. Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme.

    Science.gov (United States)

    Arques, Carlos G; Doohan, Roisin; Sharpe, James; Torres, Miguel

    2007-10-01

    Regionalization of embryonic fields into independent units of growth and patterning is a widespread strategy during metazoan development. Compartments represent a particular instance of this regionalization, in which unit coherence is maintained by cell lineage restriction between adjacent regions. Lineage compartments have been described during insect and vertebrate development. Two common characteristics of the compartments described so far are their occurrence in epithelial structures and the presence of signaling regions at compartment borders. Whereas Drosophila compartmental organization represents a background subdivision of embryonic fields that is not necessarily related to anatomical structures, vertebrate compartment borders described thus far coincide with, or anticipate, anatomical or cell-type discontinuities. Here, we describe a general method for clonal analysis in the mouse and use it to determine the topology of clone distribution along the three limb axes. We identify a lineage restriction boundary at the limb mesenchyme dorsoventral border that is unrelated to any anatomical discontinuity, and whose lineage restriction border is not obviously associated with any signaling center. This restriction is the first example in vertebrates of a mechanism of primordium subdivision unrelated to anatomical boundaries. Furthermore, this is the first lineage compartment described within a mesenchymal structure in any organism, suggesting that lineage restrictions are fundamental not only for epithelial structures, but also for mesenchymal field patterning. No lineage compartmentalization was found along the proximodistal or anteroposterior axes, indicating that patterning along these axes does not involve restriction of cell dispersion at specific axial positions.

  3. Early lens ablation causes dramatic long-term effects on the shape of bones in the craniofacial skeleton of Astyanax mexicanus.

    Directory of Open Access Journals (Sweden)

    Megan Dufton

    Full Text Available The Mexican tetra, Astyanax mexicanus, exists as two morphs of a single species, a sighted surface morph and a blind cavefish. In addition to eye regression, cavefish have an increased number of taste buds, maxillary teeth and have an altered craniofacial skeleton compared to the sighted morph. We investigated the effect the lens has on the development of the surrounding skeleton, by ablating the lens at different time points during ontogeny. This unique long-term study sheds light on how early embryonic manipulations on the eye can affect the shape of the adult skull more than a year later, and the developmental window during which time these effects occur. The effects of lens ablation were analyzed by whole-mount bone staining, immunohistochemisty and landmark based morphometric analyzes. Our results indicate that lens ablation has the greatest impact on the skeleton when it is ablated at one day post fertilisation (dpf compared to at four dpf. Morphometric analyzes indicate that there is a statistically significant difference in the shape of the supraorbital bone and suborbital bones four through six. These bones expand into the eye orbit exhibiting plasticity in their shape. Interestingly, the number of caudal teeth on the lower jaw is also affected by lens ablation. In contrast, the shape of the calvariae, the length of the mandible, and the number of mandibular taste buds are unaltered by lens removal. We demonstrate the plasticity of some craniofacial elements and the stability of others in the skull. Furthermore, this study highlights interactions present between sensory systems during early development and sheds light on the cavefish phenotype.

  4. How the embryonic chick brain twists

    OpenAIRE

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A.

    2016-01-01

    During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left–right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic m...

  5. Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.

    Science.gov (United States)

    Goodwin, Alice F; Larson, Jacinda R; Jones, Kyle B; Liberton, Denise K; Landan, Maya; Wang, Zhifeng; Boekelheide, Anne; Langham, Margaret; Mushegyan, Vagan; Oberoi, Snehlata; Brao, Rosalie; Wen, Timothy; Johnson, Ramsey; Huttner, Kenneth; Grange, Dorothy K; Spritz, Richard A; Hallgrímsson, Benedikt; Jheon, Andrew H; Klein, Ophir D

    2014-09-01

    Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

  6. The imaging findings of metastatic neuroblastoma in the craniofacial bone in children

    International Nuclear Information System (INIS)

    Bian Xin; Wang Zhenchang; Xian Junfang; Li Mei; Yan Fei; Chen Qinghua; Yang Bentao; Chang Qinglin; Tian Qichang; Liu Zhonglin

    2009-01-01

    Objective: To investigate the characteristic imaging findings of metastatic neuroblastoma in the craniofacial bone in children. Methods: Imaging findings in 12 patients with metastatic neuroblastoma in the craniofacial bone were analyzed retrospectively. Among them, 10 patients undenvent plain CT scan, 6 underwent MRI and 7 underwent whole body single-photon emission computed tomography bone scanning. Results: In the 10 patients with CT images, lytic bone destruction and soft tissue masses were found in 9 eases, in which periosteal reaction was observed in 8 patients with spiculated periosteal reaction in 3 patients. The remaining 1 patient didn't show any abnormalities on CT images but had abnormal findings in bone scanning. Six patients with MR images showed abnormal signal intensity in the bone marrow of the craniofacial bone and adjacent soft tissue masses. Postcontrast T 1 -weighted imaging in 5 patients demonstrated remarkable enhancement of the bone marrow and soft tissue masses. Bone scanning of 7 patients showed abnormal foci of increased radionuclide activity of the craniofacial bone in 7 patients and metastasis at other body parts in 6 patients. Conclusion: The metastatic neuroblastoma in the craniofacial bone has its characteristic imaging findings which are helpful for correct diagnosis. (authors)

  7. Three-Dimensional Bioprinting for Regenerative Dentistry and Craniofacial Tissue Engineering.

    Science.gov (United States)

    Obregon, F; Vaquette, C; Ivanovski, S; Hutmacher, D W; Bertassoni, L E

    2015-09-01

    Craniofacial tissues are organized with complex 3-dimensional (3D) architectures. Mimicking such 3D complexity and the multicellular interactions naturally occurring in craniofacial structures represents one of the greatest challenges in regenerative dentistry. Three-dimensional bioprinting of tissues and biological structures has been proposed as a promising alternative to address some of these key challenges. It enables precise manufacture of various biomaterials with complex 3D architectures, while being compatible with multiple cell sources and being customizable to patient-specific needs. This review describes different 3D bioprinting methods and summarizes how different classes of biomaterials (polymer hydrogels, ceramics, composites, and cell aggregates) may be used for 3D biomanufacturing of scaffolds, as well as craniofacial tissue analogs. While the fabrication of scaffolds upon which cells attach, migrate, and proliferate is already in use, printing of all the components that form a tissue (living cells and matrix materials together) to produce tissue constructs is still in its early stages. In summary, this review seeks to highlight some of the key advantages of 3D bioprinting technology for the regeneration of craniofacial structures. Additionally, it stimulates progress on the development of strategies that will promote the translation of craniofacial tissue engineering from the laboratory bench to the chair side. © International & American Associations for Dental Research 2015.

  8. Forecasting craniofacial growth in individuals with class III malocclusion by computational modelling.

    Science.gov (United States)

    Auconi, Pietro; Scazzocchio, Marco; Defraia, Efisio; McNamara, James A; Franchi, Lorenzo

    2014-04-01

    To develop a mathematical model that adequately represented the pattern of craniofacial growth in class III subject consistently, with the goal of using this information to make growth predictions that could be amenable to longitudinal verification and clinical use. A combination of computational techniques (i.e. Fuzzy clustering and Network analysis) was applied to cephalometric data derived from 429 untreated growing female patients with class III malocclusion to visualize craniofacial growth dynamics and correlations. Four age groups of subjects were examined individually: from 7 to 9 years of age, from 10 to 12 years, from 13 to 14 years, and from 15 to 17 years. The connections between pathway components of class III craniofacial growth can be visualized from Network profiles. Fuzzy clustering analysis was able to define further growth patterns and coherences of the traditionally reported dentoskeletal characteristics of this structural imbalance. Craniofacial growth can be visualized as a biological, space-constraint-based optimization process; the prediction of individual growth trajectories depends on the rate of membership to a specific 'winner' cluster, i.e. on a specific individual growth strategy. The reliability of the information thus gained was tested to forecast craniofacial growth of 28 untreated female class III subjects followed longitudinally. The combination of Fuzzy clustering and Network algorithms allowed the development of principles for combining multiple auxological cephalometric features into a joint global model and to predict the individual risk of the facial pattern imbalance during growth.

  9. Customized Polymethyl Methacrylate Implants for the Reconstruction of Craniofacial Osseous Defects

    Directory of Open Access Journals (Sweden)

    André Luis Fernandes da Silva

    2014-01-01

    Full Text Available Craniofacial defects represent alterations in the anatomy and morphology of the cranial vault and the facial bones that potentially affect an individual’s psychological and social well-being. Although a variety of techniques and restorative procedures have been described for the reconstruction of the affected area, polymethyl methacrylate (PMMA, a biocompatible and nondegradable acrylic resin-based implant, is the most widely used alloplastic material for such craniomaxillofacial reconstruction. The aim of this study was to describe a technique for aesthetic and functional preoperative customized reconstruction of craniofacial bone defects from a small series of patients offered by the Brazilian public health system. Three adult male patients attended consultation with chief complaints directly related to their individual craniofacial bone defects. With the aid of multislice computed tomography scans and subsequent fabrication of the three-dimensional craniofacial prototype, custom-made PMMA implants were fabricated preoperatively. Under general anesthesia, with access to the craniofacial defects with a coronal approach, the PMMA implants were adapted and fixated to the facial skeleton with titanium plates and screws. Postoperative evaluation demonstrated uneventful recovery and an excellent aesthetic result. Customized prefabricated PMMA implants manufactured over the rapid prototyping models proved to be effective and feasible.

  10. Craniofacial morphology and sleep apnea in children with obstructed upper airways: differences between genders.

    Science.gov (United States)

    Di Francesco, Renata; Monteiro, Roberta; Paulo, Maria Luiza de Melo; Buranello, Fernando; Imamura, Rui

    2012-06-01

    To correlate sleep apnea with craniofacial characteristics and facial patterns according to gender. In this prospective survey we studied 77 male and female children (3-12 years old) with an upper airway obstruction due to tonsil and adenoid enlargement. Children with lung problems, neurological disorders and syndromes, obstructive septal deviation, previous orthodontic treatment, orthodontic surgeries or oral surgeries, or obesity were excluded. Patients were subjected to physical examinations, nasal fiberoptic endoscopy, teleradiography for cephalometric analysis, and polysomnography. Cephalometric analysis included the following skeletal craniofacial measurements: facial axis (FA), facial depth (FD), mandibular plane angle (MP), lower facial height (LFH), mandibular arch (MA), and vertical growth coefficient (VERT) index. The prevalence of sleep apnea was 46.75% with no statistical difference between genders. Among children with obstructive sleep apnea (Apneia Hypopnea Index - AHI ≥ 1) boys had higher AHI values than girls. A predominance of the dolichofacial pattern (81.9%) was observed. The following skeletal craniofacial measurements correlated with AHI in boys: FD (r(s)=-0.336/p=0.020), MP (r(s)=0.486/p=0.00), and VERT index (r(s)=-0.337/p=0.019). No correlations between craniofacial measurements and AHI were identified in girls. Craniofacial morphology may influence the severity of sleep apnea in boys but not in girls. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Application of three-dimensional computed tomography in craniofacial clinical practice and research.

    Science.gov (United States)

    Anderson, P J; Yong, R; Surman, T L; Rajion, Z A; Ranjitkar, S

    2014-06-01

    Following the invention of the first computed tomography (CT) scanner in the early 1970s, many innovations in three-dimensional (3D) diagnostic imaging technology have occurred, leading to a wide range of applications in craniofacial clinical practice and research. Three-dimensional image analysis provides superior and more detailed information compared with conventional plain two-dimensional (2D) radiography, with the added benefit of 3D printing for preoperative treatment planning and regenerative therapy. Current state-of-the-art multidetector CT (MDCT), also known as medical CT, has an important role in the diagnosis and management of craniofacial injuries and pathology. Three-dimensional cone beam CT (CBCT), pioneered in the 1990s, is gaining increasing popularity in dental and craniofacial clinical practice because of its faster image acquisition at a lower radiation dose, but sound guidelines are needed to ensure its optimal clinical use. Recent innovations in micro-computed tomography (micro-CT) have revolutionized craniofacial biology research by enabling higher resolution scanning of teeth beyond the capabilities of MDCT and CBCT, presenting new prospects for translational clinical research. Even after four decades of refinement, CT technology continues to advance and broaden the horizons of craniofacial clinical practice and phenomics research. © 2014 Australian Dental Association.

  12. Mesenchymal stem cells: New players in retinopathy therapy

    Directory of Open Access Journals (Sweden)

    Rajashekhar eGangaraju

    2014-04-01

    Full Text Available Retinopathies in human and animal models have shown to occur through loss of pericytes resulting in edema formation, excessive immature retinal angiogenesis, and neuronal apoptosis eventually leading to blindness. In recent years, the concept of regenerating terminally differentiated organs with a cell-based therapy has evolved. The cells used in these approaches are diverse and include tissue specific endogenous stem cells, endothelial progenitor (EPC, embryonic stem cells, induced pluripotent stem cells (iPSC and mesenchymal stem cells (MSC. Recently, MSC derived from the stromal fraction of adipose tissue have been shown to possess pluripotent differentiation potential in vitro. These adipose stromal cells (ASC have been differentiated in a number of laboratories to osteogenic, myogenic, vascular and adipocytic cell phenotypes. In vivo, ASC have been shown to have functional and phenotypic overlap with pericytes lining microvessels in adipose tissues. Furthermore, these cells either in paracrine mode or physical proximity with endothelial cells, promoted angiogenesis, improved ischemia reperfusion, protected from myocardial infarction and are neuroprotective. Owing to the easy isolation procedure and abundant supply, fat derived ASC are a more preferred source of autologous mesenchymal cells compared to bone marrow MSC. In this review we present evidence that these readily available ASC from minimally invasive liposuction will facilitate translation of ASC research into patients with retinal diseases in the near future.

  13. Hypoxia activated EGFR signaling induces epithelial to mesenchymal transition (EMT.

    Directory of Open Access Journals (Sweden)

    Ashish Misra

    Full Text Available Metastasis is a multi-step process which requires the conversion of polarized epithelial cells to mesenchymal cells, Epithelial-Mesenchymal Transition (EMT. EMT is essential during embryonic morphogenesis and has been implicated in the progression of primary tumors towards metastasis. Hypoxia is known to induce EMT; however the molecular mechanism is still poorly understood. Using the A431 epithelial cancer cell line, we show that cells grown under hypoxic conditions migrated faster than cells grown under normal oxygen environment. Cells grown under hypoxia showed reduced adhesion to the extracellular matrix (ECM probably due to reduced number of Vinculin patches. Growth under hypoxic conditions also led to down regulation of E-cadherin and up regulation of vimentin expression. The increased motility of cells grown under hypoxia could be due to redistribution of Rac1 to the plasma membrane as opposed to increased expression of Rac1. EGF (Epidermal Growth Factor is a known inducer of EMT and growth of A431 cells in the absence of oxygen led to increased expression of EGFR (EGF Receptor. Treatment of A431 cells with EGF led to reduced cell adhesion to ECM, increased cell motility and other EMT characteristics. Furthermore, this transition was blocked by the monoclonal antibody Cetuximab. Cetuximab also blocked the hypoxia-induced EMT suggesting that cell growth under hypoxic conditions led to activation of EGFR signaling and induction of EMT phenotype.

  14. Characterization of craniofacial sutures using the finite element method.

    Science.gov (United States)

    Maloul, Asmaa; Fialkov, Jeffrey; Wagner, Diane; Whyne, Cari M

    2014-01-03

    Characterizing the biomechanical behavior of sutures in the human craniofacial skeleton (CFS) is essential to understand the global impact of these articulations on load transmission, but is challenging due to the complexity of their interdigitated morphology, the multidirectional loading they are exposed to and the lack of well-defined suture material properties. This study aimed to quantify the impact of morphological features, direction of loading and suture material properties on the mechanical behavior of sutures and surrounding bone in the CFS. Thirty-six idealized finite element (FE) models were developed. One additional specimen-specific FE model was developed based on the morphology obtained from a µCT scan to represent the morphological complexity inherent in CFS sutures. Outcome variables of strain energy (SE) and von Mises stress (σvm) were evaluated to characterize the sutures' biomechanical behavior. Loading direction was found to impact the relationship between SE and interdigitation index and yielded varied patterns of σvm in both the suture and surrounding bone. Adding bone connectivity reduced suture strain energy and altered the σvm distribution. Incorporating transversely isotropic material properties was found to reduce SE, but had little impact on stress patterns. High-resolution µCT scanning of the suture revealed a complex morphology with areas of high and low interdigitations. The specimen specific suture model results were reflective of SE absorption and σvm distribution patterns consistent with the simplified FE results. Suture mechanical behavior is impacted by morphologic factors (interdigitation and connectivity), which may be optimized for regional loading within the CFS. © 2013 Elsevier Ltd. All rights reserved.

  15. The heterogeneity of craniofacial morphology in Prader-Willi patients.

    Science.gov (United States)

    Belengeanu, D; Bratu, Cristina; Stoian, Monica; Motoc, A; Ormerod, Eli; Podariu, Angela Codruţa; Farcaş, Simona; Andreescu, Nicoleta

    2012-01-01

    Prader-Willi syndrome is a complex genetic disorder with narrow spectrum of facial phenotypic signs, which make the clinical diagnosis difficult in some cases. There are several reports describing the craniofacial appearance of Prader-Willi patients, but there are only a few cephalometric studies for these patients. In this study were included 18 patients with Prader-Willi syndrome and a control group of 18 subjects of both sexes selected based on specific criteria. The cephalometric radiographs of the patients were taken using the standardized technique with centric teeth in occlusion and lips in relaxed position. Angular, horizontal and linear measurements were analyzed for the study group and for the control group. We established that in Prader-Willi patients, there is a decrease of the majority of parameters but the degree of this reduction varies widely between patients and clinically typical facies not always have smaller measurements which can be found in an unusual facies. Facial dysmorphism in Prader-Willi patients varies a group ranging from miss proportions that do not alter the facial architecture as regard of facial typology, skeletal class and pattern of development to a severe disturbance of those. There is a degree of clinical heterogeneity between subjects with Prader-Willi syndrome on clinical evaluation and cephalometric study confirms the heterogeneity for this patients. Because the identification of smaller dimensions for majority of parameters in children and adults, the possibility of developmental delay or growth retardation delay can be excluded. These findings are important for the orthodontist for optimum timing of orthodontic management of patients with Prader-Willi syndrome.

  16. Bioactive Nano-fibrous Scaffold for Vascularized Craniofacial Bone Regeneration

    DEFF Research Database (Denmark)

    Prabha, Rahul Damodaran; Kraft, David Christian Evar; Harkness, Linda

    2018-01-01

    the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA) - poly (ε) caprolactone (PCL) - Bioceramic (HAB), namely, PVA-PCL-HAB. The scaffold prepared by dual...... electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic poly (ε) caprolactone (PCL) by combination with a hydrophilic polyvinyl alcohol (PVA) and the bioceramic (HAB) can contribute to enhance osteo-conductivity. We characterized the physicochemical...... and biocompatibility properties of the new scaffold material. Our results indicate PVA-PCL-HAB scaffolds support attachment and growth of stromal stem cells; (human bone marrow skeletal (mesenchymal) stem cells (hMSC) and dental pulp stem cells (DPSC)). In addition, the scaffold supported in vitro osteogenic...

  17. Three-dimensional analysis of craniofacial bones using three-dimensional computer tomography

    International Nuclear Information System (INIS)

    Ono, Ichiro; Ohura, Takehiko; Kimura, Chu

    1989-01-01

    Three-dimensional computer tomography (3DCT) was performed in patients with various diseases to visualize stereoscopically the deformity of the craniofacial bones. The data obtained were analyzed by the 3DCT analyzing system. A new coordinate system was established using the median sagittal plane of the face (a plane passing through sella, nasion and basion) on the three-dimensional image. Three-dimensional profilograms were prepared for detailed analysis of the deformation of craniofacial bones for cleft lip and palate, mandibular prognathia and hemifacial microsomia. For patients, asymmetry in the frontal view and twist-formed complicated deformities were observed, as well as deformity of profiles in the anteroposterior and up-and-down directions. A newly developed technique allows three-dimensional visualization of changes in craniofacial deformity. It would aid in determining surgical strategy, including crani-facial surgery and maxillo-facial surgery, and in evaluating surgical outcome. (N.K.)

  18. Three-dimensional analysis of craniofacial bones using three-dimensional computer tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Ichiro; Ohura, Takehiko; Kimura, Chu (Hokkaido Univ., Sapporo (Japan). School of Medicine) (and others)

    1989-08-01

    Three-dimensional computer tomography (3DCT) was performed in patients with various diseases to visualize stereoscopically the deformity of the craniofacial bones. The data obtained were analyzed by the 3DCT analyzing system. A new coordinate system was established using the median sagittal plane of the face (a plane passing through sella, nasion and basion) on the three-dimensional image. Three-dimensional profilograms were prepared for detailed analysis of the deformation of craniofacial bones for cleft lip and palate, mandibular prognathia and hemifacial microsomia. For patients, asymmetry in the frontal view and twist-formed complicated deformities were observed, as well as deformity of profiles in the anteroposterior and up-and-down directions. A newly developed technique allows three-dimensional visualization of changes in craniofacial deformity. It would aid in determining surgical strategy, including crani-facial surgery and maxillo-facial surgery, and in evaluating surgical outcome. (N.K.).

  19. Clinical Application of Three-Dimensional Printing Technology in Craniofacial Plastic Surgery

    Directory of Open Access Journals (Sweden)

    Jong Woo Choi

    2015-05-01

    Full Text Available Three-dimensional (3D printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models.

  20. Clinical Application of Three-Dimensional Printing Technology in Craniofacial Plastic Surgery

    Science.gov (United States)

    Kim, Namkug

    2015-01-01

    Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models. PMID:26015880

  1. Vertebrate Embryonic Cleavage Pattern Determination.

    Science.gov (United States)

    Hasley, Andrew; Chavez, Shawn; Danilchik, Michael; Wühr, Martin; Pelegri, Francisco

    2017-01-01

    The pattern of the earliest cell divisions in a vertebrate embryo lays the groundwork for later developmental events such as gastrulation, organogenesis, and overall body plan establishment. Understanding these early cleavage patterns and the mechanisms that create them is thus crucial for the study of vertebrate development. This chapter describes the early cleavage stages for species representing ray-finned fish, amphibians, birds, reptiles, mammals, and proto-vertebrate ascidians and summarizes current understanding of the mechanisms that govern these patterns. The nearly universal influence of cell shape on orientation and positioning of spindles and cleavage furrows and the mechanisms that mediate this influence are discussed. We discuss in particular models of aster and spindle centering and orientation in large embryonic blastomeres that rely on asymmetric internal pulling forces generated by the cleavage furrow for the previous cell cycle. Also explored are mechanisms that integrate cell division given the limited supply of cellular building blocks in the egg and several-fold changes of cell size during early development, as well as cytoskeletal specializations specific to early blastomeres including processes leading to blastomere cohesion. Finally, we discuss evolutionary conclusions beginning to emerge from the contemporary analysis of the phylogenetic distributions of cleavage patterns. In sum, this chapter seeks to summarize our current understanding of vertebrate early embryonic cleavage patterns and their control and evolution.

  2. FGF10: A multifunctional mesenchymal-epithelial signaling growth factor in development, health, and disease.

    Science.gov (United States)

    Itoh, Nobuyuki

    2016-04-01

    The FGF family comprises 22 members with diverse functions in development and health. FGF10 specifically activates FGFR2b in a paracrine manner with heparan sulfate as a co-factor. FGF10and FGFR2b are preferentially expressed in the mesenchyme and epithelium, respectively. FGF10 is a mesenchymal signaling molecule in the epithelium. FGF10 knockout mice die shortly after birth due to the complete absence of lungs as well as fore- and hindlimbs. FGF10 is also essential for the development of multiple organs. The phenotypes of Fgf10 knockout mice are very similar to those of FGFR2b knockout mice, indicating that FGF10 acts as a ligand that is specific to FGFR2b in mouse multi-organ development. FGF10 also plays roles in epithelial-mesenchymal transition, the repair of tissue injury, and embryonic stem cell differentiation. In humans, FGF10 loss-of-function mutations result in inherited diseases including aplasia of lacrimal and salivary gland, lacrimo-auriculo-dento-digital syndrome, and chronic obstructive pulmonary disease. FGF10 is also involved in the oncogenicity of pancreatic and breast cancers. Single nucleotide polymorphisms in FGF10 are also potential risk factors for limb deficiencies, cleft lip and palate, and extreme myopia. These findings indicate that FGF10 is a crucial paracrine signal from the mesenchyme to epithelium for development, health, and disease. Copyright © 2015. Published by Elsevier Ltd.

  3. Generation of functional islets from human umbilical cord and placenta derived mesenchymal stem cells.

    Science.gov (United States)

    Kadam, Sachin; Govindasamy, Vijayendran; Bhonde, Ramesh

    2012-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been used for allogeneic application in tissue engineering but have certain drawbacks. Therefore, mesenchymal stem cells (MSCs) derived from other adult tissue sources have been considered as an alternative. The human umbilical cord and placenta are easily available noncontroversial sources of human tissue, which are often discarded as biological waste, and their collection is noninvasive. These sources of MSCs are not subjected to ethical constraints, as in the case of embryonic stem cells. MSCs derived from umbilical cord and placenta are multipotent and have the ability to differentiate into various cell types crossing the lineage boundary towards endodermal lineage. The aim of this chapter is to provide a detailed reproducible cookbook protocol for the isolation, propagation, characterization, and differentiation of MSCs derived from human umbilical cord and placenta with special reference to harnessing their potential towards pancreatic/islet lineage for utilization as a cell therapy product. We show here that mesenchymal stromal cells can be extensively expanded from umbilical cord and placenta of human origin retaining their multilineage differentiation potential in vitro. Our report indicates that postnatal tissues obtained as delivery waste represent a rich source of mesenchymal stromal cells, which can be differentiated into functional islets employing three-stage protocol developed by our group. These islets could be used as novel in vitro model for screening hypoglycemics/insulin secretagogues, thus reducing animal experimentation for this purpose and for the future human islet transplantation programs to treat diabetes.

  4. Relationships between craniocervical posture and pain-related disability in patients with cervico-craniofacial pain

    Science.gov (United States)

    López-de-Uralde-Villanueva, Ibai; Beltran-Alacreu, Hector; Paris-Alemany, Alba; Angulo-Díaz-Parreño, Santiago; La Touche, Roy

    2015-01-01

    Objectives This cross-sectional correlation study explored the relationships between craniocervical posture and pain-related disability in patients with chronic cervico-craniofacial pain (CCFP). Moreover, we investigated the test–retest intrarater reliability of two craniocervical posture measurements: head posture (HP) and the sternomental distance (SMD). Methods Fifty-three asymptomatic subjects and 60 CCFP patients were recruited. One rater measured HP and the SMD using a cervical range of motion device and a digital caliper, respectively. The Spanish versions of the neck disability index and the craniofacial pain and disability inventory were used to assess pain-related disability (neck disability and craniofacial disability, respectively). Results We found no statistically significant correlations between craniocervical posture and pain-related disability variables (HP and neck disability [r=0.105; P>0.05]; HP and craniofacial disability [r=0.132; P>0.05]; SMD and neck disability [r=0.126; P>0.05]; SMD and craniofacial disability [r=0.195; P>0.05]). A moderate positive correlation was observed between HP and SMD for both groups (asymptomatic subjects, r=0.447; CCFP patients, r=0.52). Neck disability was strongly positively correlated with craniofacial disability (r=0.79; Pposture, but these differences were very small (mean difference =1.44 cm for HP; 6.24 mm for SMD). The effect sizes reached by these values were estimated to be small for SMD (d=0.38) and medium for HP (d=0.76). Conclusion The results showed no statistically significant correlations between craniocervical posture and variables of pain-related disability, but a strong correlation between the two variables of disability was found. Our findings suggest that small differences between CCFP patients and asymptomatic subjects exist with respect to the two measurements used to assess craniocervical posture (HP and SMD), and these measures demonstrated high test–retest intrarater reliability for

  5. Flood, disaster, and turmoil: social issues in cleft and craniofacial care and crisis relief.

    Science.gov (United States)

    Strauss, Ronald P; van Aalst, John A; Fox, Lynn; Stein, Margot; Moses, Michael; Cassell, Cynthia H

    2011-11-01

    To examine social issues in the conduct of cleft and craniofacial care through relief programs in disrupted crisis contexts. Social, health policy, and ethical analyses. At best, craniofacial team care is multidisciplinary, coordinated, and sustained, requiring a long-term relationship between team members, patients, and families. Disasters and societal turmoil interrupt such relationships, causing craniofacial care to become a secondary concern. Providing craniofacial team care in a crisis setting requires rebuilding disrupted coordination and communication. Crisis relief care involves a complex set of expectations and responsibilities and raises issues such as (1) quality assurance, infection control, appropriate standards of care, and follow-up care/continuity; (2) equity of access to services and clinical ethics in the context of war and/or deprivation; (3) training of visitors in the local nation or site; (4) disciplinary composition of teams, interprofessional communication/rivalry, and credentials of clinicians; (5) ownership of the site and local visitor relations; (6) fundraising and marketing strategies; and (7) ethical issues in the doctor-patient relationship. Specific ethical standards for international cleft and craniofacial care delivery also apply to domestic and global crisis relief contexts. Guidance on issues related to professional experience, informed consent, and continuity of care will help care providers address social and ethical issues raised in crisis relief programs. This paper proposes that the Position Paper of the American Cleft Palate-Craniofacial Association (ACPA) on International Treatment Programs should be used as a template to develop and disseminate a set of standards that apply to crisis relief.

  6. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

    Energy Technology Data Exchange (ETDEWEB)

    Biemann, Ronald, E-mail: ronald.biemann@medizin.uni-halle.de [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Navarrete Santos, Anne [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Navarrete Santos, Alexander [Department of Cardiothoracic Surgery, Martin Luther University, Faculty of Medicine, Halle (Germany); Riemann, Dagmar [Department of Immunology, Martin Luther University, Faculty of Medicine, Halle (Germany); Knelangen, Julia [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Blueher, Matthias [Department of Medicine, University of Leipzig, Leipzig (Germany); Koch, Holger [Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Ruhr-University Bochum, Bochum (Germany); Fischer, Bernd [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  7. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

    International Nuclear Information System (INIS)

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blüher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-01

    Highlights: ► Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). ► The adipogenic impact depends strongly on the window of exposure. ► Bisphenol A reduces the potential of MSC to differentiate into adipocytes. ► DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. ► BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPARγ2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 μM) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 μM) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  8. Cytomegalovirus-induced embryopathology: mouse submandibular salivary gland epithelial-mesenchymal ontogeny as a model

    Directory of Open Access Journals (Sweden)

    Huang Jing

    2006-09-01

    Full Text Available Abstract Background Human studies suggest, and mouse models clearly demonstrate, that cytomegalovirus (CMV is dysmorphic to early organ and tissue development. CMV has a particular tropism for embryonic salivary gland and other head mesenchyme. CMV has evolved to co-opt cell signaling networks so to optimize replication and survival, to the detriment of infected tissues. It has been postulated that mesenchymal infection is the critical step in disrupting organogenesis. If so, organogenesis dependent on epithelial-mesenchymal interactions would be particularly vulnerable. In this study, we chose to model the vulnerability by investigating the cell and molecular pathogenesis of CMV infected mouse embryonic submandibular salivary glands (SMGs. Results We infected E15 SMG explants with mouse CMV (mCMV. Active infection for up to 12 days in vitro results in a remarkable cell and molecular pathology characterized by atypical ductal epithelial hyperplasia, apparent epitheliomesenchymal transformation, oncocytic-like stromal metaplasia, β-catenin nuclear localization, and upregulation of Nfkb2, Relb, Il6, Stat3, and Cox2. Rescue with an antiviral nucleoside analogue indicates that mCMV replication is necessary to initiate and maintain SMG dysmorphogenesis. Conclusion mCMV infection of embryonic mouse explants results in dysplasia, metaplasia, and, possibly, anaplasia. The molecular pathogenesis appears to center around the activation of canonical and, perhaps more importantly, noncanonical NFκB. Further, COX-2 and IL-6 are important downstream effectors of embryopathology. At the cellular level, there appears to be a consequential interplay between the transformed SMG cells and the surrounding extracellular matrix, resulting in the nuclear translocation of β-catenin. From these studies, a tentative framework has emerged within which additional studies may be planned and performed.

  9. Craniofacial norms in white adult males. Final report 1 Oct 80-30 Sep 83

    International Nuclear Information System (INIS)

    Kapur, K.K.; Lestrel, P.

    1983-01-01

    The objective of this investigation was to establish clinical 'norms' of craniofacial skeletal orientation and the associated soft tissue facial profile for adult white males. Lateral and frontal cephalometric radiographs and study casts taken on 305 white males, with 28 or more teeth and 25-75 years of age, were used to develop these craniofacial standards. The goal of the research program has been to develop a computerized approach based upon dentofacial templates for the fabrication of complete dentures and to define clinical standards that can be applied in assessing the prosthodontic and orthodontic treatment needs of adult patients

  10. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

  11. [Embryonic stem cells. Future perspectives].

    Science.gov (United States)

    Groebner, M; David, R; Franz, W M

    2006-05-01

    Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.

  12. Efficient differentiation of human embryonic stem cells to definitive endoderm.

    Science.gov (United States)

    D'Amour, Kevin A; Agulnick, Alan D; Eliazer, Susan; Kelly, Olivia G; Kroon, Evert; Baetge, Emmanuel E

    2005-12-01

    The potential of human embryonic stem (hES) cells to differentiate into cell types of a variety of organs has generated much excitement over the possible use of hES cells in therapeutic applications. Of great interest are organs derived from definitive endoderm, such as the pancreas. We have focused on directing hES cells to the definitive endoderm lineage as this step is a prerequisite for efficient differentiation to mature endoderm derivatives. Differentiation of hES cells in the presence of activin A and low serum produced cultures consisting of up to 80% definitive endoderm cells. This population was further enriched to near homogeneity using the cell-surface receptor CXCR4. The process of definitive endoderm formation in differentiating hES cell cultures includes an apparent epithelial-to-mesenchymal transition and a dynamic gene expression profile that are reminiscent of vertebrate gastrulation. These findings may facilitate the use of hES cells for therapeutic purposes and as in vitro models of development.

  13. Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells.

    Science.gov (United States)

    Lefevre, James G; Chiu, Han S; Combes, Alexander N; Vanslambrouck, Jessica M; Ju, Ali; Hamilton, Nicholas A; Little, Melissa H

    2017-03-15

    Human pluripotent stem cells, after directed differentiation in vitro , can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation can also reform embryonic organ structure after tissue disruption. It has previously been demonstrated that dissociated embryonic kidneys can recreate component epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis. Here, we investigate the timing and underlying mechanisms driving self-organisation after dissociation of the embryonic kidney using time-lapse imaging, high-resolution confocal analyses and mathematical modelling. Organotypic self-organisation sufficient for nephron initiation was observed within a 24 h period. This involved cell movement, with structure emerging after the clustering of ureteric epithelial cells, a process consistent with models of random cell movement with preferential cell adhesion. Ureteric epithelialisation rapidly followed the formation of ureteric cell clusters with the reformation of nephron-forming niches representing a later event. Disruption of P-cadherin interactions was seen to impair this ureteric epithelial cell clustering without affecting epithelial maturation. This understanding could facilitate improved regulation of patterning within organoids and facilitate kidney engineering approaches guided by cell-cell self-organisation. © 2017. Published by The Company of Biologists Ltd.

  14. Unilateral cleft lip and palate : treatment outcome and long-term craniofacial growth

    NARCIS (Netherlands)

    Nollet, Petrus Josephus Paulinus Maria

    2006-01-01

    Treatment results of children with a complete Unilateral Cleft Lip and Palate (UCLP) from the Cleft Palate Craniofacial Unit of the Radboud University Nijmegen Medical Centre were evaluated and compared with prominent European cleft centers. Treatment outcome of the Nijmegen patients with UCLP and

  15. 78 FR 75929 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

    Science.gov (United States)

    2013-12-13

    ... Craniofacial Research Special Emphasis Panel; Review of NIDCR Institutional Career Development Award K12... review and evaluate grant applications. Place: National Institutes of Health, One Democracy Plaza, 6701 Democracy Boulevard, Bethesda, MD 20892. Contact Person: Victor Henriquez, Ph.D., Scientific Review Officer...

  16. G-Protein α-Subunit Gsα Is Required for Craniofacial Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Run Lei

    Full Text Available The heterotrimeric G protein subunit Gsα couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA activation. Gsα is ubiquitously expressed in many cell types; however, the role of Gsα in neural crest cells (NCCs remains unclear. Here we report that NCCs-specific Gsα knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsα knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsα knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsα in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development.

  17. Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome

    DEFF Research Database (Denmark)

    Dixon, J; Brakebusch, C; Fässler, R

    2000-01-01

    mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site...

  18. Effectiveness of the cervical vertebral maturation method to predict postpeak circumpubertal growth of craniofacial structures.

    NARCIS (Netherlands)

    Fudalej, P.S.; Bollen, A.M.

    2010-01-01

    INTRODUCTION: Our aim was to assess effectiveness of the cervical vertebral maturation (CVM) method to predict circumpubertal craniofacial growth in the postpeak period. METHODS: The CVM stage was determined in 176 subjects (51 adolescent boys and 125 adolescent girls) on cephalograms taken at the

  19. 75 FR 28031 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

    Science.gov (United States)

    2010-05-19

    ... Craniofacial Research Special Emphasis Panel; Teleconference Review of R03 Applications for Mechanisms, Models... Research Special Emphasis Panel; Teleconference Review of Small Research Grants for Data Analysis and....121, Oral Diseases and Disorders Research, National Institutes of Health, HHS). Dated: May 13, 2010...

  20. Inheritance of craniofacial features in Colombian families with class III malocclusion

    Directory of Open Access Journals (Sweden)

    L Otero

    2010-02-01

    Full Text Available L Otero, L Quintero, D Champsaur, E SimancaPontificia Universidad Javeriana, Bogotá, ColombiaIntroduction: The inheritance of class III malocclusion has been well documented, but the inheritance of craniofacial structures in Colombian families with this malocclusion has been not yet reported.Patients and methods: The study sample of 25 families comprised 186 untreated orthodontic individuals from 8 to 60 years old. Pedigrees were drawn using Cyrillic software. Complete family histories for each proband were ascertained and the affection status of relatives was confirmed by lateral cephalograms and facial and dental photographs. Analysis of variance and odds ratio test for each parameter was performed to estimate inheritance from parents to offspring and to determine similar phenotypic features in relatives.Results: The analysis of the pedigrees suggests autosomal dominant inheritance. The craniofacial characteristics that showed more resemblance between parents and offspring were middle facial height, shorter anterior cranial base and mandibular prognathism. In contrast the protrusion of upper lip and maxillary retrusion were the phenotypic features that contributed to class III in the majority of families.Conclusion: Knowledge of the inheritance of craniofacial phenotypes in class III malocclusion will enable the design of new therapies to treat this malocclusion.Keywords: inheritance, craniofacial, phenotype, class III malocclusion

  1. The FaceBase Consortium: A comprehensive program to facilitate craniofacial research

    Science.gov (United States)

    Hochheiser, Harry; Aronow, Bruce J.; Artinger, Kristin; Beaty, Terri H.; Brinkley, James F.; Chai, Yang; Clouthier, David; Cunningham, Michael L.; Dixon, Michael; Donahue, Leah Rae; Fraser, Scott E.; Hallgrimsson, Benedikt; Iwata, Junichi; Klein, Ophir; Marazita, Mary L.; Murray, Jeffrey C.; Murray, Stephen; de Villena, Fernando Pardo-Manuel; Postlethwait, John; Potter, Steven; Shapiro, Linda; Spritz, Richard; Visel, Axel; Weinberg, Seth M.; Trainor, Paul A.

    2012-01-01

    The FaceBase Consortium consists of ten interlinked research and technology projects whose goal is to generate craniofacial research data and technology for use by the research community through a central data management and integrated bioinformatics hub. Funded by the National Institute of Dental and Craniofacial Research (NIDCR) and currently focused on studying the development of the middle region of the face, the Consortium will produce comprehensive datasets of global gene expression patterns, regulatory elements and sequencing; will generate anatomical and molecular atlases; will provide human normative facial data and other phenotypes; conduct follow up studies of a completed genome-wide association study; generate independent data on the genetics of craniofacial development, build repositories of animal models and of human samples and data for community access and analysis; and will develop software tools and animal models for analyzing and functionally testing and integrating these data. The FaceBase website (http://www.facebase.org) will serve as a web home for these efforts, providing interactive tools for exploring these datasets, together with discussion forums and other services to support and foster collaboration within the craniofacial research community. PMID:21458441

  2. Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

    Science.gov (United States)

    Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

    2007-07-01

    To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

  3. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction.

    Science.gov (United States)

    Friedman, C D; Costantino, P D; Takagi, S; Chow, L C

    1998-01-01

    BoneSource-hydroxyapatite cement is a new self-setting calcium phosphate cement biomaterial. Its unique and innovative physical chemistry coupled with enhanced biocompatibility make it useful for craniofacial skeletal reconstruction. The general properties and clinical use guidelines are reviewed. The biomaterial and surgical applications offer insight into improved outcomes and potential new uses for hydroxyapatite cement systems.

  4. Recurrent meningitis and frontal encephalocele as delayed complications of craniofacial trauma.

    Science.gov (United States)

    Gumussoy, Murat; Ugur, Omer; Cukurova, Ibrahim; Uluyol, Sinan

    2014-03-01

    Frontal sinus back table fractures are seen rarely; also, typical presentation of frontal sinus encephalocele as a delayed complication of frontal sinus fracture is seen more rarely. We present a case of frontal encephalocele and recurrent meningitis as delayed complications of craniofacial trauma. Diagnosis, management, and treatment approaches of these complications are discussed.

  5. Utility of MDP bone SPECT in the detection of osseous invasion in craniofacial malignancies

    International Nuclear Information System (INIS)

    Saeed, S.; Haq, S.; Sohaib, M.; Khan, A.N.

    2002-01-01

    Aim: The study was designed to observe the role of SPECT imaging for the detection of osseous invasion in craniofacial malignancies. Material and Methods: Radionuclide bone imaging with Tc-99m MDP was done on 20 patients with different craniofacial malignancies. The planar imaging comprised of anterior, lateral and oblique lateral views of the skull. SPECT imaging was done taking 64 views of the skull in a 360 deg. circular path, each of 40 seconds with 128x128 matrix. Visual interpretation of the scans was done and a score of 0, 1, or 2 allocated, representing a lesion as definitely absent, doubtful or definitely present, respectively. SPECT images were compared with planar scans. Results: SPECT was proven superior to planar imaging and radiographs in detection as well as efficient demonstration of the extent of osseous invasion of a craniofacial cancer. The sensitivity was 100% for SPECT, 83.3% for planar and 33.3% for radiographs. Conclusion: SPECT imaging of the skull can serve as an extremely useful complementary investigation in the patients with craniofacial malignancies to assess them for osseous invasion, particularly in tumors likely to invade the skull base

  6. Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

    NARCIS (Netherlands)

    Prins, Sandra A.; van Dijk, Monique; van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.

    2008-01-01

    The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h

  7. Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

    NARCIS (Netherlands)

    Prins, Sandra A.; Van Dijk, Monique; Van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.

    Background: The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods: During surgery all infants (6 months-2 years) received a rectal loading dose of 40

  8. The influence of craniofacial to standing height proportion on perceived attractiveness.

    Science.gov (United States)

    Naini, F B; Cobourne, M T; McDonald, F; Donaldson, A N A

    2008-10-01

    An idealised male image, based on Vitruvian Man, was created. The craniofacial height was altered from a proportion of 1/6 to 1/10 of standing height, creating 10 images shown in random order to 89 observers (74 lay people; 15 clinicians), who ranked the images from the most to the least attractive. The main outcome was the preference ranks of image attractiveness given by the observers. Linear regressions were used to assess what influences the choice for the most and the least attractive images, followed by a multivariate rank ordinal logistic regression to test the influence of age, gender, ethnicity and professional status of the observer. A craniofacial height to standing height proportion of 1/7.5 was perceived as the most attractive (36%), followed by a proportion of 1/8 (26%). The images chosen as most attractive by more than 10% of observers had a mean proportion of 1/7.8(min=1/7; max=1/8.5). The images perceived as most unattractive had a proportion of 1/6 and 1/10. The choice of images was not influenced by the age, gender, ethnicity or professional status of the observers. The ideal craniofacial height to standing height proportion is in the range 1/7 to 1/8.5. This finding should be considered when planning treatment to alter craniofacial or facial height.

  9. Psychological impact of visible differences in patients with congenital craniofacial anomalies.

    Science.gov (United States)

    Singh, Varun Pratap; Moss, Timothy P

    2015-01-01

    Patients with craniofacial anomalies often have appearance concerns and related social anxiety which can affect their quality of life. This study assessed the psychological impact of facial and dental appearance in patients with craniofacial anomalies in comparison to a general population control group. The study involved 102 adult patients (51% male) with congenital craniofacial anomalies and 102 controls (49% male). Both groups completed the Nepali version of Derriford Appearance Scale (DAS) and the Psychological Impact of Dental Aesthetic Questionnaire (PIDAQ) in a clinical setting to assess appearance-related distress, avoidance, and anxiety. There was a significant difference between patients and controls on both PIDAQ (mean score for patients 33.25 ± 9.45 while for controls 27.52 ± 5.67, p experienced greater negative psychological impact of living with their appearance (PIDAQ) and more appearance-related distress (DAS) than controls. DAS scores were not associated with gender. There was no association of the place of residence (rural vs. urban) with PIDAQ or DAS59 scores. There is a significant psychological impact of altered facial and dental appearance in patients with craniofacial anomalies compared to controls. There was no effect of locality (rural/urban) on the psychological impact of facial and dental appearance in patients.

  10. Mild traumatic brain injury diagnosis frequently remains unrecorded in subjects with craniofacial fractures.

    Science.gov (United States)

    Puljula, Jussi; Cygnel, Hanna; Mäkinen, Elina; Tuomivaara, Veli; Karttunen, Vesa; Karttunen, Ari; Hillbom, Matti

    2012-12-01

    Traumatic brain injuries (TBI) in subjects with craniofacial fractures are usually diagnosed by emergency room physicians. We investigated how often TBI remains unrecorded in these subjects, and whether diagnostic accuracy has improved after the implementation of new TBI guidelines. All subjects with craniofacial fractures admitted to Oulu University Hospital in 1999 and in 2007 were retrospectively identified. New guidelines for improving the diagnostic accuracy of TBI were implemented between 2000 and 2006. Clinical symptoms of TBI were gathered from notes on hospital charts and compared to the recorded diagnoses at discharge. Logistic regression was used to identify independent predictors for TBI to remain unrecorded. Of 194 subjects with craniofacial fracture, 111(57%) had TBI, 40 in 1999 and 71 in 2007. Fifty-one TBIs (46%) remained unrecorded at discharge, 48 being mild and 3 moderate-to-severe. Subjects with unrecorded TBI were significantly less frequently referred to follow-up visits. Failures to record the TBI diagnosis were less frequent (29/71, 41%) in 2007 than in 1999 (22/40, 55%), but the difference was not statistically significant. The most significant independent predictor for this failure was the clinical specialty (other than neurology/neurosurgery) of the examining physician (palcohol intoxication did not hamper the diagnosis of TBI. TBIs remain frequently unrecorded in subjects with craniofacial fractures. Recording of mild TBI slightly but insignificantly improved after the implementation of new guidelines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Radiography, Computed Tomography and Magnetic Resonance Imaging of Craniofacial Structures in Pig

    Czech Academy of Sciences Publication Activity Database

    Kyllar, M.; Štembírek, Jan; Putnová, I.; Stehlík, L.; Odehnalová, S.; Buchtová, Marcela

    2014-01-01

    Roč. 43, č. 6 (2014), s. 435-452 ISSN 0340-2096 R&D Projects: GA ČR(CZ) GP304/08/P289 Institutional support: RVO:67985904 Keywords : craniofacial structures in pig Subject RIV: EA - Cell Biology Impact factor: 0.672, year: 2014

  12. Obstructive sleep apnea prevents the expected difference in craniofacial growth of boys and girls

    Directory of Open Access Journals (Sweden)

    Maria Ligia Juliano

    2013-01-01

    Full Text Available OBJECTIVES: It was to compare cephalometric measures of mouth-breather boys and girls and with the cephalometric pattern observed in obstructive sleep apnea syndrome (OSAS patients. METHODS: Craniofacial measurements of lateral cephalometric radiographs obtained from 144 children aged 7-14 years were compared between boys and girls, and both were compared to cephalometric pattern of OSAS patients. RESULTS: Mouth-breather boys and girls had no gender differences regarding to craniofacial morphology while nose-breather boys and girls showed those expected differences. Nose-breather boys presented a more retruded mandible and proinclined upper incisor when compared to nose-breather girls, but mouth-breather boys and girls had no differences. The measure NS.GoGn was the only variable with an interaction with gender and breathing. CONCLUSIONS: There were no cephalometric difference in mouth breather-boys and girls related to normal growth, suggesting that oral breathing make the same craniofacial morphology and both have craniofacial morphology close to that of OSAS patients.

  13. 3-D analysis of tooth formation and eruption in patients with craniofacial anomalies

    DEFF Research Database (Denmark)

    Kreiborg, Sven; Larsen, Per; Bro-Nielsen, Morten

    1996-01-01

    A number of craniofacial anomalies or syndromes involve severe disturbances of tooth formation and eruption (e.g. Apert syndrome, Crouzon syndrome, tricho-dento-osseous syndrome, cleidocranial dysplasia, and cleft lip and palate). So far, studies of these dental problems have been limited to two...

  14. In vivo bone strain and finite-element modeling of the craniofacial haft in catarrhine primates

    Science.gov (United States)

    Ross, Callum F; Berthaume, Michael A; Dechow, Paul C; Iriarte-Diaz, Jose; Porro, Laura B; Richmond, Brian G; Spencer, Mark; Strait, David

    2011-01-01

    Hypotheses regarding patterns of stress, strain and deformation in the craniofacial skeleton are central to adaptive explanations for the evolution of primate craniofacial form. The complexity of craniofacial skeletal morphology makes it difficult to evaluate these hypotheses with in vivo bone strain data. In this paper, new in vivo bone strain data from the intraorbital surfaces of the supraorbital torus, postorbital bar and postorbital septum, the anterior surface of the postorbital bar, and the anterior root of the zygoma are combined with published data from the supraorbital region and zygomatic arch to evaluate the validity of a finite-element model (FEM) of a macaque cranium during mastication. The behavior of this model is then used to test hypotheses regarding the overall deformation regime in the craniofacial haft of macaques. This FEM constitutes a hypothesis regarding deformation of the facial skeleton during mastication. A simplified verbal description of the deformation regime in the macaque FEM is as follows. Inferior bending and twisting of the zygomatic arches about a rostrocaudal axis exerts inferolaterally directed tensile forces on the lateral orbital wall, bending the wall and the supraorbital torus in frontal planes and bending and shearing the infraorbital region and anterior zygoma root in frontal planes. Similar deformation regimes also characterize the crania of Homo and Gorilla under in vitro loading conditions and may be shared among extant catarrhines. Relatively high strain magnitudes in the anterior root of the zygoma suggest that the morphology of this region may be important for resisting forces generated during feeding. PMID:21105871

  15. Current and emerging basic science concepts in bone biology: implications in craniofacial surgery.

    Science.gov (United States)

    Oppenheimer, Adam J; Mesa, John; Buchman, Steven R

    2012-01-01

    Ongoing research in bone biology has brought cutting-edge technologies into everyday use in craniofacial surgery. Nonetheless, when osseous defects of the craniomaxillofacial skeleton are encountered, autogenous bone grafting remains the criterion standard for reconstruction. Accordingly, the core principles of bone graft physiology continue to be of paramount importance. Bone grafts, however, are not a panacea; donor site morbidity and operative risk are among the limitations of autologous bone graft harvest. Bone graft survival is impaired when irradiation, contamination, and impaired vascularity are encountered. Although the dura can induce calvarial ossification in children younger than 2 years, the repair of critical-size defects in the pediatric population may be hindered by inadequate bone graft donor volume. The novel and emerging field of bone tissue engineering holds great promise as a limitless source of autogenous bone. Three core constituents of bone tissue engineering have been established: scaffolds, signals, and cells. Blood supply is the sine qua non of these components, which are used both individually and concertedly in regenerative craniofacial surgery. The discerning craniofacial surgeon must determine the proper use for these bone graft alternatives, while understanding their concomitant risks. This article presents a review of contemporary and emerging concepts in bone biology and their implications in craniofacial surgery. Current practices, areas of controversy, and near-term future applications are emphasized.

  16. Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients

    NARCIS (Netherlands)

    Smeele, L. E.; Kostense, P. J.; van der Waal, I.; Snow, G. B.

    1997-01-01

    To evaluate the possible value of chemotherapy in the treatment of craniofacial osteosarcoma (CFOS). In a systematic review, data of 201 patients (age, 36.6 +/- 19.0 years [mean +/- SD]) from 20 uncontrolled series on CFOS indexed in Medline and Excerpta Medica between 1974 and 1994 were pooled; 180

  17. 78 FR 24762 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-26

    ..., Bethesda, MD 20892. Contact Person: Alicia J. Dombroski, Ph.D., Director, Division of Extramural Activities... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...

  18. 75 FR 13561 - National Institute of Dental & Craniofacial Research; Notice of Meeting

    Science.gov (United States)

    2010-03-22

    ... Floor, 31 Center Drive, Conference Room 10, Bethesda, MD 20892. Contact Person: Alicia J. Dombroski, PhD... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as...

  19. 75 FR 13562 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-22

    ..., Room 117, Bethesda, MD 20892. Contact Person: Alicia J. Dombroski, PhD, Director, Division of... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...

  20. 77 FR 68136 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2012-11-15

    .... Contact Person: Alicia J. Dombroski, Ph.D., Director, Division of Extramural Activities, National... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...

  1. 76 FR 22111 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2011-04-20

    ..., MD 20892. Contact Person: Alicia J. Dombroski, PhD, Director, Division of Extramural Activities, Natl... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...

  2. 77 FR 14816 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2012-03-13

    ... & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...: National Institutes of Health, Building 30, 30 Center Drive, 117, Bethesda, MD 20892 Contact Person: Alicia J. Dombroski, Ph.D., Director, Division of Extramural Activities, Natl Inst of Dental and...

  3. 75 FR 69451 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2010-11-12

    ... Person: Alicia J. Dombroski, PhD, Director, Division of Extramural Activities, Natl Inst of Dental and... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...

  4. 76 FR 66077 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-25

    ... Center Drive, 117, Bethesda, MD 20892 Contact Person: Alicia J. Dombroski, PhD, Director, Division of... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act...

  5. 77 FR 49820 - National Institute of Dental & Craniofacial Research; Notice of Meeting

    Science.gov (United States)

    2012-08-17

    ... Center Drive, 6th Floor, 10, Bethesda, MD 20892. Contact Person: Alicia J. Dombroski, Ph.D., Director... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as...

  6. Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme.

    Science.gov (United States)

    Tucker, A S; Al Khamis, A; Sharpe, P T

    1998-08-01

    Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions. Bmp4 has been identified as a candidate signalling molecule in these interactions, initially as an epithelial signal and then later at the bud stage as a mesenchymal signal (Vainio et al. [1993] Cell 75:45-58). A target gene for Bmp4 signalling is the homeobox gene Msx-1, identified by the ability of recombinant Bmp4 protein to induce expression in mesenchyme. There is, however, no evidence that Bmp4 is the endogenous inducer of Msx-1 expression. Msx-1 and Bmp-4 show dynamic, interactive patterns of expression in oral epithelium and ectomesenchyme during the early stages of tooth development. In this study, we compare the temporal and spatial expression of these two genes to determine whether the changing expression patterns of these genes are consistent with interactions between the two molecules. We show that changes in Bmp-4 expression precede changes in Msx-1 expression. At embryonic day (E)10.5-E11.0, expression patterns are consistent with BMP4 from the epithelium, inducing or maintaining Msx-1 in underlying mesenchyme. At E11.5, Bmp-4 expression shifts from epithelium to mesenchyme and is rapidly followed by localised up-regulation of Msx-1 expression at the sites of Bmp-4 expression. Using cultured explants of developing mandibles, we confirm that exogenous BMP4 is capable of replacing the endogenous source in epithelium and inducing Msx-1 gene expression in mesenchyme. By using noggin, a BMP inhibitor, we show that endogenous Msx-1 expression can be inhibited at E10.5 and E11.5, providing the first evidence that endogenous Bmp-4 from the epithelium is responsible for regulating the early spatial expression of Msx-1. We also show that the mesenchymal shift in Bmp-4 is responsible for up-regulating Msx-1 specifically at the sites of future tooth formation. Thus, we establish that a reciprocal series of interactions act to restrict expression of both genes to future

  7. Ellis van Creveld2 is required for postnatal craniofacial bone development

    Science.gov (United States)

    Badri, Mohammed K.; Zhang, Honghao; Ohyama, Yoshio; Venkitapathi, Sundharamani; Kamiya, Nobuhiro; Takeda, Haruko; Ray, Manas; Scott, Greg; Tsuji, Takehito; Kunieda, Tetsuo; Mishina, Yuji; Mochida, Yoshiyuki

    2016-01-01

    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3- and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ~20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. PMID:27090777

  8. Cranio-facial remodeling in domestic dogs is associated with changes in larynx position.

    Science.gov (United States)

    Plotsky, Kyle; Rendall, Drew; Chase, Kevin; Riede, Tobias

    2016-06-01

    The hyo-laryngeal complex is a multi-segmented structure integrating the oral and pharyngeal cavities and thus a variety of critical functions related to airway control, feeding, and vocal communication. Currently, we lack a complete understanding of how the hyoid complex, and the functions it mediates, can also be affected by changes in surrounding cranio-facial dimensions. Here, we explore these relationships in a breed of domestic dog, the Portuguese Water Dog, which is characterized by strong cranio-facial variation. We used radiographic images of the upper body and head of 55 adult males and 51 adult females to obtain detailed measures of cranio-facial variation and hyoid anatomy. Principal components analysis revealed multiple orthogonal dimensions of cranio-facial variation, some of which were associated with significant differences in larynx position: the larynx occupied a more descended position in individuals with shorter, broader faces than in those with longer, narrower faces. We then tested the possibility that caudal displacement of the larynx in brachycephalic individuals might reflect a degree of tongue crowding resulting from facial shortening and reduction of oral and pharyngeal spaces. A cadaver sample was used to obtain detailed measurements of constituent bones of the hyoid skeleton and of the tongue body, and their relationships to cranio-facial size and shape and overall body size supported the tongue-crowding hypothesis. Considering the presence of descended larynges in numerous mammalian taxa, our findings establish an important precedent for the possibility that laryngeal descent can be initiated, and even sustained, in part in response to remodeling of the face and cranium for selective pressures unrelated to vocal production. These integrated changes could also have been involved in hominin evolution, where the different laryngeal positions in modern humans compared with nonhuman primates have been traditionally linked to the evolution

  9. Computer vision and soft computing for automatic skull-face overlay in craniofacial superimposition.

    Science.gov (United States)

    Campomanes-Álvarez, B Rosario; Ibáñez, O; Navarro, F; Alemán, I; Botella, M; Damas, S; Cordón, O

    2014-12-01

    Craniofacial superimposition can provide evidence to support that some human skeletal remains belong or not to a missing person. It involves the process of overlaying a skull with a number of ante mortem images of an individual and the analysis of their morphological correspondence. Within the craniofacial superimposition process, the skull-face overlay stage just focuses on achieving the best possible overlay of the skull and a single ante mortem image of the suspect. Although craniofacial superimposition has been in use for over a century, skull-face overlay is still applied by means of a trial-and-error approach without an automatic method. Practitioners finish the process once they consider that a good enough overlay has been attained. Hence, skull-face overlay is a very challenging, subjective, error prone, and time consuming part of the whole process. Though the numerical assessment of the method quality has not been achieved yet, computer vision and soft computing arise as powerful tools to automate it, dramatically reducing the time taken by the expert and obtaining an unbiased overlay result. In this manuscript, we justify and analyze the use of these techniques to properly model the skull-face overlay problem. We also present the automatic technical procedure we have developed using these computational methods and show the four overlays obtained in two craniofacial superimposition cases. This automatic procedure can be thus considered as a tool to aid forensic anthropologists to develop the skull-face overlay, automating and avoiding subjectivity of the most tedious task within craniofacial superimposition. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Mesenchymal progenitor cells for the osteogenic lineage.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  11. Implications of TGFβ on transcriptome and cellular biofunctions of palatal mesenchyme

    Directory of Open Access Journals (Sweden)

    Xiujuan eZhu

    2012-04-01

    Full Text Available Development of the palate comprises sequential stages of growth, elevation and fusion of the palatal shelves. The mesenchymal component of palates plays a major role in early phases of palatogenesis, such as growth and elevation. Failure in these steps may result in cleft palate, the second most common birth defect in the world. These early stages of palatogenesis require precise and chronological orchestration of key physiological processes, such as growth, proliferation, differentiation, migration, and apoptosis. There is compelling evidence for the vital role of TGFβ-mediated regulation of palate development. We hypothesized that the isoforms of TGFβ regulate different cellular biofunctions of the palatal mesenchyme to various extents. Human embryonic palatal mesenchyme (HEPM cells were treated with TGFβ1, β2, and β3 for microarray-based gene expression studies in order to identify the roles of TGFβ in the transcriptome of the palatal mesenchyme. Following normalization and modeling of 28,869 human genes, 566 transcripts were detected as differentially expressed in TGFβ-treated HEPM cells. Out of these altered transcripts, 234 of them were clustered in cellular biofunctions, including growth and proliferation, development, morphology, movement, cell cycle, and apoptosis. Biological interpretation and network analysis of the genes active in cellular biofunctions were performed using IPA. Among the differentially expressed genes, 11 of them were previously identified as being crucial for palatogenesis (EDN1, INHBA, LHX8, PDGFC, PIGA, RUNX1, SNAI1, SMAD3, TGFβ1, TGFβ2, and TGFβR1. These genes were used for a merged interaction network with cellular behaviors. Overall, we have determined that more than 2% of human transcripts were differentially expressed in response to TGFβ treatment in HEPM cells. Our results suggest that both TGFβ1 and TGFβ2 orchestrate major cellular biofunctions within the palatal mesenchyme in vitro by

  12. Guidelines for human embryonic stem cell research

    National Research Council Canada - National Science Library

    Committee on Guidelines for Human Embryonic Stem Cell Research, National Research Council

    2005-01-01

    Since 1998, the volume of research being conducted using human embryonic stem (hES) cells has expanded primarily using private funds because of restrictions on the use of federal funds for such research...

  13. Biomechanical forces promote embryonic haematopoiesis

    Science.gov (United States)

    Adamo, Luigi; Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Mack, Peter J.; Gracia-Sancho, Jorge; Suchy-Dicey, Astrid; Yoshimoto, Momoko; Lensch, M. William; Yoder, Mervin C.; García-Cardeña, Guillermo; Daley, George Q.

    2009-01-01

    Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system1,2. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3–5), a master regulator of haematopoiesis, and give rise to haematopoietic cells4. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential6. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41+c-Kit+ haematopoietic progenitor cells7,concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the paraaortic splanchnopleura/aorta–gonads–mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling8, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development. PMID:19440194

  14. Mesenchymal and embryonic characteristics of stem cells obtained from mouse dental pulp

    DEFF Research Database (Denmark)

    Guimarães, Elisalva Teixeira; Cruz, Gabriela Silva; de Jesus, Alan Araújo

    2011-01-01

    abnormalities was evaluated by G banding. RESULTS: The mouse dental pulp stem cells (mDPSC) were highly proliferative, plastic-adherent, and exhibited a polymorphic morphology predominantly with stellate or fusiform shapes. The presence of cell clusters was observed in cultures of mDPSC. Some cells were...

  15. Femtosecond laser pulses for chemical-free embryonic and mesenchymal stem cell differentiation

    CSIR Research Space (South Africa)

    Mthunzi, P

    2011-08-01

    Full Text Available Owing to their self renewal and pluripotency properties, stem cells can efficiently advance current therapies in tissue regeneration and/or engineering. Under appropriate culture conditions in vitro, pluripotent stem cells can be primed...

  16. Tooth agenesis and craniofacial morphology in pre-orthodontic children with and without morphological deviations in the upper cervical spine

    DEFF Research Database (Denmark)

    Jasemi, Ashkan; Sonnesen, Liselotte

    2016-01-01

    AIM: To analyze differences in prevalence and pattern of tooth agenesis and craniofacial morphology between non syndromic children with tooth agenesis with and without upper cervical spine morphological deviations and to analyze associations between craniofacial morphology and tooth agenesis...... in the two groups together. METHODS: One hundred and twenty-six pre-orthodontic children with tooth agenesis were divided into two groups with (19 children, mean age 11.9) and without (107 children, mean age 11.4) upper spine morphological deviations. Visual assessment of upper spine morphology...... and measurements of craniofacial morphology were performed on lateral cephalograms. Tooth agenesis was evaluated from orthopantomograms. RESULTS: No significant differences in tooth agenesis and craniofacial morphology were found between children with and without upper spine morphological deviations (2.2 ± 1.6 vs...

  17. Three-dimensional image display by CT data processing and clinical applications in orthopaedics and craniofacial surgery

    International Nuclear Information System (INIS)

    Zonneveld, F.W.; Akkerveeken, P.F. van; Koornneef, L.

    1988-01-01

    The methods of generating three-dimensional images from two-dimensional CT data are described. Four cases are reported explaining its use in the planning of orthopaedic and craniofacial surgery. (orig.) [de

  18. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  19. Exploring the Medical and Psychosocial Concerns of Adolescents and Young Adults With Craniofacial Microsomia: A Qualitative Study.

    Science.gov (United States)

    Hamilton, Kayla V; Ormond, Kelly E; Moscarello, Tia; Bruce, Janine S; Bereknyei Merrell, Sylvia; Chang, Kay W; Bernstein, Jonathan A

    2018-01-01

    This study explores the experiences of adolescents and young adults with craniofacial microsomia, including the impact of growing up with this craniofacial condition on daily life and sense of self. The results may guide future research on optimally supporting individuals with craniofacial microsomia during this critical life phase. Participants were recruited through a craniofacial center, online patient support groups, and social media sites. Eleven individual semistructured interviews with participants between 12 and 22 years old were conducted by a single interviewer, transcribed, iteratively coded, and thematically analyzed. Five themes were evident in the data: (1) impact on personal growth and character development, (2) negative psychosocial impact, (3) deciding to hide or reveal the condition, (4) desire to make personal surgical decisions, and (5) struggles with hearing loss. We identified both medical and psychosocial concerns prevalent among adolescents with craniofacial microsomia. Although adolescents with craniofacial microsomia exhibit considerable resilience, the challenges they face impact their sense of self and should be addressed through psychosocial support and counseling. Further research should investigate the potential benefit of the wider use of hearing aids, as well as the involvement of patients in decision-making about reconstructive ear surgery.

  20. The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus.

    Directory of Open Access Journals (Sweden)

    John N Griffin

    2015-03-01

    Full Text Available The production of ribosomes is ubiquitous and fundamental to life. As such, it is surprising that defects in ribosome biogenesis underlie a growing number of symptomatically distinct inherited disorders, collectively called ribosomopathies. We previously determined that the nucleolar protein, NOL11, is essential for optimal pre-rRNA transcription and processing in human tissue culture cells. However, the role of NOL11 in the development of a multicellular organism remains unknown. Here, we reveal a critical function for NOL11 in vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly expressed in the developing cranial neural crest (CNC of both amphibians and mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA transcription and processing, increased apoptosis, and abnormal development of the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype, but not the underlying ribosome biogenesis defect, demonstrating an evolutionarily conserved control mechanism through which ribosome-impaired craniofacial cells are removed. Excessive activation of this mechanism impairs craniofacial development. Together, our findings reveal a novel requirement for Nol11 in craniofacial development, present the first frog model of a ribosomopathy, and provide further insight into the clinically important relationship between specific ribosome biogenesis proteins and craniofacial cell survival.

  1. Postoperative assessment of surgical results using three dimensional surface reconstruction CT (3D-CT) in a craniofacial anomaly

    International Nuclear Information System (INIS)

    Nishimura, Jiro; Sato, Kaoru; Nishimoto, Hiroshi; Tsukiyama, Takashi; Fujioka, Mutsuhisa; Akagawa, Tetsuya.

    1988-01-01

    In 1983, Michael W. Vannier and Jeffrey L. Marsh developed a computer method that reconstructs three dimensional (3D) born and soft tissue surfaces, given a high resolution CT scan-series of the facial skeleton. This method has been applied to craniofacial anomalies, basal encephaloceles, and musculoskeletal anomalies. In this study, a postoperative assessment of the craniofacial surgical results has been accomplished using this 3D-CT in 2 children with craniofacial dysmorphism. The authors discuss the advantages of this 3D-CT imaging method in the postoperative assessments of craniofacial anomalies. Results are detailed in the following listing : 1) a postoperative 3D-CT reveals the anatomical details corrected by the craniofacial surgery more precisely and stereographically than conventional radiological methods ; 2) secondary changes of the cranium after the surgery, such as bony formation in the area of the osteotomy and postoperative asymmetric deformities, are detected early by the 3D-CT imaging technique, and, 3) 3D-CT mid-sagittal and top axial views of the intracranial skull base are most useful in postoperative assessments of the surgical results. Basesd on our experience, we expect that three dimensional surface reconstructions from CT scans will become to be used widely in the postoperative assessments of the surgical results of craniofacial anomalies. (author)

  2. Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1

    International Nuclear Information System (INIS)

    Pei, Xin-Hong; Lv, Xin-Quan; Li, Hui-Xiang

    2014-01-01

    Highlights: • Depletion of Sox5 inhibits breast cancer proliferation, migration, and invasion. • Sox5 transactivates Twist1 expression. • Sox5 induces epithelial to mesenchymal transition through transactivation of Twist1 expression. - Abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression

  3. Research of TGF-beta1 Inducing Lung Adencarcinoma PC9 Cells to Mesenchymal Cells Transition

    Directory of Open Access Journals (Sweden)

    Xiaofeng CHEN

    2010-01-01

    Full Text Available Background and objective It has been proven that epithelial-mesenchymal transition (EMT not only correlated with embryonic development but also could promote tumor invasion and metastasis. Transforming growth factor beta-1 (TGF-β1 has been identified as the main inducer of tumor EMT. The aim of this study was to investigate the effects of TGF-β1 on EMT and PI3K/AKT signaling pathway in lung adencarcinoma PC9 cells. Methods Cultured PC9 cells were treated with different concentrations of TGF-β1 for 48 h. The morphological changes were observed under phase-contrast microscopy; EMT relative marker protein changes were assessed by Western blot and immunoflurescence staining. In addition, the expression of AKT and P-AKT were also measured by Western blot. Results The data showed that TGF-β1 could induce PC9 morphological alteration from epithelial to mesenchymal and upregulate the expression of mesenchymal maker protein Fibronectin. Obviously, the expression of P-AKT was downregulated by TGF-β1 treatment for 48 h. Conclusion TGF-β1 might induce EMT of PC9 cells , accompanied by the changes of PI3K/AKT signaling pathway.

  4. Coupled Reversible and Irreversible Bistable Switches Underlying TGFβ-induced Epithelial to Mesenchymal Transition

    Science.gov (United States)

    Tian, Xiao-Jun; Zhang, Hang; Xing, Jianhua

    2013-01-01

    Epithelial to mesenchymal transition (EMT) plays an important role in embryonic development, tissue regeneration, and cancer metastasis. Whereas several feedback loops have been shown to regulate EMT, it remains elusive how they coordinately modulate EMT response to TGF-β treatment. We construct a mathematical model for the core regulatory network controlling TGF-β-induced EMT. Through deterministic analyses and stochastic simulations, we show that EMT is a sequential two-step program in which an epithelial cell first is converted to partial EMT then to the mesenchymal state, depending on the strength and duration of TGF-β stimulation. Mechanistically the system is governed by coupled reversible and irreversible bistable switches. The SNAIL1/miR-34 double-negative feedback loop is responsible for the reversible switch and regulates the initiation of EMT, whereas the ZEB/miR-200 feedback loop is accountable for the irreversible switch and controls the establishment of the mesenchymal state. Furthermore, an autocrine TGF-β/miR-200 feedback loop makes the second switch irreversible, modulating the maintenance of EMT. Such coupled bistable switches are robust to parameter variation and molecular noise. We provide a mechanistic explanation on multiple experimental observations. The model makes several explicit predictions on hysteretic dynamic behaviors, system response to pulsed stimulation, and various perturbations, which can be straightforwardly tested. PMID:23972859

  5. Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives

    Directory of Open Access Journals (Sweden)

    Zomer HD

    2015-09-01

    Full Text Available Helena D Zomer,1 Atanásio S Vidane,1 Natalia N Gonçalves,1 Carlos E Ambrósio2 1Department of Surgery, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil; 2Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil Abstract: Mesenchymal stem cells have awakened a great deal of interest in regenerative medicine due to their plasticity, and immunomodulatory and anti-inflammatory properties. They are high-yield and can be acquired through noninvasive methods from adult tissues. Moreover, they are nontumorigenic and are the most widely studied. On the other hand, induced pluripotent stem (iPS cells can be derived directly from adult cells through gene reprogramming. The new iPS technology avoids the embryo destruction or manipulation to generate pluripotent cells, therefore, are exempt from ethical implication surrounding embryonic stem cell use. The pre-differentiation of iPS cells ensures the safety of future approaches. Both mesenchymal stem cells and iPS cells can be used for autologous cell transplantations without the risk of immune rejection and represent a great opportunity for future alternative therapies. In this review we discussed the therapeutic perspectives using mesenchymal and iPS cells. Keywords: cell transplantation, cell therapy, iPS, MSC

  6. Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development

    Directory of Open Access Journals (Sweden)

    Bringas Pablo

    2008-03-01

    Full Text Available Abstract Background Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM. Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives. Results E11 mouse mandibular processes (MANs were infected with mouse CMV (mCMV for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins. Conclusion Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal

  7. Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis

    Science.gov (United States)

    Nie, Xuguang; Wang, Qin; Jiao, Kai

    2014-01-01

    MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th pharyngeal arch artery (PAA) remodeling was affected, resulting in interrupted aortic arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and pharyngeal arch artery morphogenesis. PMID:21256960

  8. Associations between craniofacial morphology, head posture, and cervical vertebral body fusions in men with sleep apnea

    DEFF Research Database (Denmark)

    Svanholt, Palle; Petri, Niels; Wildschiødtz, Gordon

    2009-01-01

    . The patients were divided into 4 groups according to fusion in the cervical vertebrae: group I, no fusions (42 subjects); group II, fusion of cervical vertebrae 2 and 3 (15 subjects); group III, occipitalization (10 subjects); and group IV, block fusion (11 subjects). Mean differences of craniofacial...... dimensions between the groups were assessed by unpaired t tests. RESULTS: No significant differences were seen between groups I and III. Between groups I and II, significant differences were seen in jaw relationship (P face height and mandibular length deviated...... significantly. No significant differences were seen in head posture. CONCLUSIONS: OSA patients with block fusions in the cervical vertebrae and fusion of 2 vertebrae differed significantly in craniofacial profile from other OSA patients....

  9. The slant of the forehead as a craniofacial feature of impulsiveness

    Directory of Open Access Journals (Sweden)

    J. David Guerrero-Apolo

    2018-03-01

    Full Text Available Objective: Impulsiveness has been the subject of much research, but little is known about the possible relationship between craniofacial anatomy and impulsiveness. The present study was designed to investigate the relationship between one aspect of craniofacial structure (the angle of inclination of the forehead and impulsiveness. Method: Photographs in profile were obtained from 131 volunteers who had been fined for driving at high speed and were undergoing a court-mandated driving license point-recovery course. They completed the Barratt Impulsiveness Scale (BIS-11, the Impulsive Behavior Scale (UPPS-P, and Zuckerman’s Sensation Seeking Scale (V. The angle of the slant of the forehead was measured with a photographic support and a protractor. Results: High positive concordance was found between forehead inclination and 14 out of the 15 impulsiveness factors studied. Conclusions: The angle of inclination of the forehead was significantly associated with self-reported impulsiveness in this sample of traffic violators.

  10. Characteristics of associated craniofacial trauma in patients with head injuries: An experience with 100 cases

    Directory of Open Access Journals (Sweden)

    Rajendra Prasad

    2009-01-01

    Full Text Available Background: Facial fractures and concomitant cranial injuries carry the significant potential for mortality and neurological morbidity mainly in young adults. Aims and Objectives: To analyze the characteristics of head injuries and associated facial injuries, the management options and outcome following cranio-facial trauma. Methods: This retrospective review was performed at Justice K. S. Hegde Charitable Hospital, and associated A. B. Shetty Memorial Institute of Dental sciences, Deralakatte, Mangalore. Following Ethical Committee approval, hospital charts and radiographs of 100 consecutive patients of cranio-facial trauma managed at the Department of Oral and Maxillofacial Surgery and Neurosurgery between January 2004 and December 2004 were reviewed. Results: Majority of the patients were in the 2nd to 4th decade (79% with a male to female ratio of -8.09:1. Road traffic accidents were the common cause of craniofacial trauma in present study (54% followed by fall from height (30%. Loss of consciousness was the most common clinical symptom (62% followed by headache (33%. Zygoma was the most commonly fractured facial bone 48.2% (alone 21.2%, in combination 27.2%. Majority of patients had mild head injury and managed conservatively in present series. Causes of surgical intervention for intracranial lesions were compound depressed fracture, contusion and intracranial hematoma. Operative indications for facial fractures were displaced facial bone fractures. Major causes of mortality were associated systemic injuries. Conclusion: Adult males are the most common victims in craniofacial trauma, and road traffic accidents were responsible for the majority. Most of the patients sustained mild head injuries and were managed conservatively. Open reduction and internal fixation with miniplates was used for displaced facial bone fractures.

  11. Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates.

    Science.gov (United States)

    Sessle, B J

    2000-01-01

    This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.

  12. Reliable classification of facial phenotypic variation in craniofacial microsomia: a comparison of physical exam and photographs.

    Science.gov (United States)

    Birgfeld, Craig B; Heike, Carrie L; Saltzman, Babette S; Leroux, Brian G; Evans, Kelly N; Luquetti, Daniela V

    2016-03-31

    Craniofacial microsomia is a common congenital condition for which children receive longitudinal, multidisciplinary team care. However, little is known about the etiology of craniofacial microsomia and few outcome studies have been published. In order to facilitate large, multicenter studies in craniofacial microsomia, we assessed the reliability of phenotypic classification based on photographs by comparison with direct physical examination. Thirty-nine children with craniofacial microsomia underwent a physical examination and photographs according to a standardized protocol. Three clinicians completed ratings during the physical examination and, at least a month later, using respective photographs for each participant. We used descriptive statistics for participant characteristics and intraclass correlation coefficients (ICCs) to assess reliability. The agreement between ratings on photographs and physical exam was greater than 80 % for all 15 categories included in the analysis. The ICC estimates were higher than 0.6 for most features. Features with the highest ICC included: presence of epibulbar dermoids, ear abnormalities, and colobomas (ICC 0.85, 0.81, and 0.80, respectively). Orbital size, presence of pits, tongue abnormalities, and strabismus had the lowest ICC, values (0.17 or less). There was not a strong tendency for either type of rating, physical exam or photograph, to be more likely to designate a feature as abnormal. The agreement between photographs and physical exam regarding the presence of a prior surgery was greater than 90 % for most features. Our results suggest that categorization of facial phenotype in children with CFM based on photographs is reliable relative to physical examination for most facial features.

  13. Severe craniofacial sclerosis with multiple anomalies in a boy and his mother

    Energy Technology Data Exchange (ETDEWEB)

    Currarino, G; Friedman, J M

    1986-09-01

    A boy is described with severe hyperostosis of the cranium and facial bones, and many other abnormalities including macrocephaly, abnormal facies, cleft palate, conductive hearing loss, speech defect, dental and digital anomalies, delayed skeletal development, short fibulas, short stature of postnatal onset, cervical kyphosis, and progressive lumbar lordosis. His mother exhibited craniofacial sclerosis, similar dental defects, and mild osteopathia striata without other abnormalities. This family may represent a previously undescribed inherited syndrome with cranial sclerosis.

  14. Severe craniofacial sclerosis with multiple anomalies in a boy and his mother

    International Nuclear Information System (INIS)

    Currarino, G.; Friedman, J.M.

    1986-01-01

    A boy is described with severe hyperostosis of the cranium and facial bones, and many other abnormalities including macrocephaly, abnormal facies, cleft palate, conductive hearing loss, speech defect, dental and digital anomalies, delayed skeletal development, short fibulas, short stature of postnatal onset, cervical kyphosis, and progressive lumbar lordosis. His mother exhibited craniofacial sclerosis, similar dental defects, and mild osteopathia striata without other abnormalities. This family may represent a previously undescribed inherited syndrome with cranial sclerosis. (orig.)

  15. Developing business opportunities from concept to end point for craniofacial surgeons.

    Science.gov (United States)

    Brown, Spencer A

    2012-01-01

    Craniofacial surgeons repair a wide variety of soft and hard tissues that produce the clinical expertise to recognize the need for an improved device or novel regenerative stem cell or use of molecules that may dramatically change the way clinical care for improved patient outcomes. The business pathway to bring a concept to clinical care requires knowledge, mentoring, and a team of experts in business and patent law.

  16. Mitochondrial DNA and craniofacial covariability of Chad Basin females indicate past population events

    Czech Academy of Sciences Publication Activity Database

    Hájek, Martin; Černý, Viktor; Brůžek, J.

    2008-01-01

    Roč. 20, č. 4 (2008), s. 465-474 ISSN 1042-0533 R&D Projects: GA ČR GA206/08/1587 Institutional research plan: CEZ:AV0Z80020508 Keywords : craniofacial morphology * mitochondrial DNA * sub - Saharan Africa * population history Sub ject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 1.976, year: 2008 http://www3.interscience.wiley.com/journal/118903453/abstract?CRETRY=1&SRETRY=0

  17. Prevention of Cutaneous Tissue Contracture During Removal of Craniofacial Implant Superstructures for CT and MRI Studies

    Directory of Open Access Journals (Sweden)

    Maureen Sullivan

    2010-04-01

    Full Text Available Objectives: Head and neck cancer patients who have lost facial parts following surgical intervention frequently require craniofacial implant retained facial prostheses for restoration. Many craniofacial implant patients require computed tomography and magnetic resonance imaging scans as part of their long-term follow-up care. Consequently removal of implant superstructures and peri-abutment tissue management is required for those studies. The purpose of the present paper was to describe a method for eliminating cranial imaging artifacts in patients with craniofacial implants.Material and Methods: Three patients wearing extraoral implant retained facial prostheses needing either computed tomography or magnetic resonance imaging studies were discussed. Peri-implant soft tissues contracture after removal of percutaneous craniofacial implant abutments during computed tomography and magnetic resonance imaging studies was prevented using a method proposed by authors. The procedure involves temporary removal of the supra-implant components prior to imaging and filling of the tissue openings with polyvinyl siloxane dental impression material.Results: Immediately after filling of the tissue openings with polyvinyl siloxane dental impression material patients were sent for the imaging studies, and were asked to return for removal of the silicone plugs and reconnection of all superstructure hardware after imaging procedures were complete. The silicone plugs were easily removed with a dental explorer. The percutaneous abutments were immediately replaced and screwed into the implants which were at the bone level.Conclusions: Presented herein method eliminates the source of artifacts and prevents contracture of percutaneous tissues upon removal of the implant abutments during imaging.

  18. Ethnical evaluation of Bangladeshi young adults in terms of morphometrically-analyzed craniofacial skeleton

    Directory of Open Access Journals (Sweden)

    Hasan Md. Rizvi

    2013-01-01

    Full Text Available Morphometric study for the craniofacial relations and variations in humans have long been used to differentiate various racial groups in physical anthropology. The objective of this study was to describe the morphological features of craniofacial skeleton in Bangladeshi young adults and to compare it with already reported standards for the Caucasian population as well as cephalometric values of other Indian races using Steiner′s reference norms. The study was conducted for 52 Bangladeshi young adults (27 male and 25 females, aged 21-27 years, having balanced and harmonious facial profiles, clinically acceptable occlusion with permanent dentition and no history of orthodontic treatment. Lateral cephalograms taken of these subjects were used for a series of morphometric analyses. Bangladeshi subjects were more protrusive skeletally and dentally than Caucasians. Furthermore, the mandibular plane angle was smaller in Bangladeshi subjects than in the Caucasians. Present results also suggest that the Astrics, Dravidians, and Armenoid who penetrated into Bengal in the early ages may have contributed substantially to the morphogenesis of craniofacial skeleton in the present Bengalis. The results of this study support the idea that a single standard of facial esthetics should not be applied to all racial and ethnic groups.

  19. Craniofacial growth in a whole rat head transplant: how does a non-functional head grow?

    Science.gov (United States)

    Sugawara, Y; Hirabayashi, S; Harii, K

    1999-01-01

    To evaluate factors intrinsic to the regulation of craniofacial bone growth, we have developed a new experimental model in which the whole head of an infant rat is transplanted to the body of an isohistogenic rat by means of microvascular anastomosis. In our model, the transplanted head has neither scars nor any moving soft tissue that could modify growth around facial bones. Using this model, we evaluated the growth pattern of the craniofacial complex by means of serial roentgenographic cephalometrics. Ten transplantations were performed using 10-day-old rats as donors and 8-week-old rats as recipients. Cephalograms were taken from the lateral direction at 10, 20, 30, and 40 days after transplantation. Several reference points were selected to analyze the growth pattern. In the present study, we conclude that the size and form of the bony complex are mainly determined genetically. There is craniofacial skeletal growth in the absence of muscle function and brain growth. Further, both the nasal cartilage and the sutures appear to be autonomous growth centers having intrinsic growth potential. Genetic or epigenetic information plays an important role at the skeletal level, but it also affects the muscles through the medium of the muscular tonus responsible for posture and other related phenomena.

  20. Decreasing the effective radiation dose in pediatric craniofacial CT by changing head position

    International Nuclear Information System (INIS)

    Didier, Ryne A.; Kuang, Anna A.; Schwartz, Daniel L.; Selden, Nathan R.; Stevens, Donna M.; Bardo, Dianna M.E.

    2010-01-01

    Children are exposed to ionizing radiation during pre- and post-operative evaluation for craniofacial surgery. The primary purpose of the study was to decrease effective radiation dose while preserving the diagnostic quality of the study. In this prospective study 49 children were positioned during craniofacial CT (CFCT) imaging with their neck fully extended into an exaggerated sniff position, parallel to the CT gantry, to eliminate the majority of the cervical spine and the thyroid gland from radiation exposure. Image-quality and effective radiation dose comparisons were made retrospectively in age-matched controls (n = 49). When compared to CT scans reviewed retrospectively, the prospective examinations showed a statistically significant decrease in z-axis length by 16% (P < 0.0001) and delivered a reduced effective radiation dose by 18% (P < 0.0001). The subjective diagnostic quality of the exams performed in the prospective arm was maintained despite a slight decrease in the quality of the brain windows. There was statistically significant improvement in the quality of the bone windows and three-dimensional reconstructed images. Altering the position of the head by extending the neck during pediatric craniofacial CT imaging statistically reduces the effective radiation dose while maintaining the diagnostic quality of the images. (orig.)

  1. A Morpholino-based screen to identify novel genes involved in craniofacial morphogenesis

    Science.gov (United States)

    Melvin, Vida Senkus; Feng, Weiguo; Hernandez-Lagunas, Laura; Artinger, Kristin Bruk; Williams, Trevor

    2014-01-01

    BACKGROUND The regulatory mechanisms underpinning facial development are conserved between diverse species. Therefore, results from model systems provide insight into the genetic causes of human craniofacial defects. Previously, we generated a comprehensive dataset examining gene expression during development and fusion of the mouse facial prominences. Here, we used this resource to identify genes that have dynamic expression patterns in the facial prominences, but for which only limited information exists concerning developmental function. RESULTS This set of ~80 genes was used for a high throughput functional analysis in the zebrafish system using Morpholino gene knockdown technology. This screen revealed three classes of cranial cartilage phenotypes depending upon whether knockdown of the gene affected the neurocranium, viscerocranium, or both. The targeted genes that produced consistent phenotypes encoded proteins linked to transcription (meis1, meis2a, tshz2, vgll4l), signaling (pkdcc, vlk, macc1, wu:fb16h09), and extracellular matrix function (smoc2). The majority of these phenotypes were not altered by reduction of p53 levels, demonstrating that both p53 dependent and independent mechanisms were involved in the craniofacial abnormalities. CONCLUSIONS This Morpholino-based screen highlights new genes involved in development of the zebrafish craniofacial skeleton with wider relevance to formation of the face in other species, particularly mouse and human. PMID:23559552

  2. A role for chemokine signaling in neural crest cell migration and craniofacial development

    Science.gov (United States)

    Killian, Eugenia C. Olesnicky; Birkholz, Denise A.; Artinger, Kristin Bruk

    2009-01-01

    Neural crest cells (NCCs) are a unique population of multipotent cells that migrate along defined pathways throughout the embryo and give rise to many diverse cell types including pigment cells, craniofacial cartilage and the peripheral nervous system (PNS). Aberrant migration of NCCs results in a wide variety of congenital birth defects including craniofacial abnormalities. The chemokine Sdf1 and its receptors, Cxcr4 and Cxcr7, have been identified as key components in the regulation of cell migration in a variety of tissues. Here we describe a novel role for the zebrafish chemokine receptor Cxcr4a in the development and migration of cranial NCCs (CNCCs). We find that loss of Cxcr4a, but not Cxcr7b results in aberrant CNCC migration, defects in the neurocranium, as well as cranial ganglia dismorphogenesis. Moreover, overexpression of either Sdf1b or Cxcr4a causes aberrant CNCC migration and results in ectopic craniofacial cartilages. We propose a model in which Sdf1b signaling from the pharyngeal arch endoderm and optic stalk to Cxcr4a expressing CNCCs is important for both the proper condensation of the CNCCs into pharyngeal arches and the subsequent patterning and morphogenesis of the neural crest derived tissues. PMID:19576198

  3. In vivo impact of Dlx3 conditional inactivation in Neural Crest-Derived Craniofacial Bones

    Science.gov (United States)

    Duverger, Olivier; Isaac, Juliane; Zah, Angela; Hwang, Joonsung; Berdal, Ariane; Lian, Jane B.; Morasso, Maria I.

    2012-01-01

    Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activity related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. PMID:22886599

  4. 3D-Printing Technologies for Craniofacial Rehabilitation, Reconstruction, and Regeneration.

    Science.gov (United States)

    Nyberg, Ethan L; Farris, Ashley L; Hung, Ben P; Dias, Miguel; Garcia, Juan R; Dorafshar, Amir H; Grayson, Warren L

    2017-01-01

    The treatment of craniofacial defects can present many challenges due to the variety of tissue-specific requirements and the complexity of anatomical structures in that region. 3D-printing technologies provide clinicians, engineers and scientists with the ability to create patient-specific solutions for craniofacial defects. Currently, there are three key strategies that utilize these technologies to restore both appearance and function to patients: rehabilitation, reconstruction and regeneration. In rehabilitation, 3D-printing can be used to create prostheses to replace or cover damaged tissues. Reconstruction, through plastic surgery, can also leverage 3D-printing technologies to create custom cutting guides, fixation devices, practice models and implanted medical devices to improve patient outcomes. Regeneration of tissue attempts to replace defects with biological materials. 3D-printing can be used to create either scaffolds or living, cellular constructs to signal tissue-forming cells to regenerate defect regions. By integrating these three approaches, 3D-printing technologies afford the opportunity to develop personalized treatment plans and design-driven manufacturing solutions to improve aesthetic and functional outcomes for patients with craniofacial defects.

  5. Influences of palatoplasty by the push-back procedure on craniofacial morphology and growth.

    Science.gov (United States)

    Iwasaki, Hiroshi; Kudo, Motonori; Yamamoto, Yuko

    2012-12-01

    For patients with a cleft palate, the push-back procedure which accompanies posterior shifting of palatal flap is thought to be most effective way of. achieving adequate velopharyngeal function. In this study, we aimed to evaluate the influences of the push-back procedure on the craniofacial morphology and its growth. Using cephalometry we compared the craniofacial morphology and growth of three groups of Japanese children, living in the same region (Hokkaido, Japan). 1) 28 children (13 girls and 15 boys) with operated submucous cleft palates at the ages of 9 and 14 respectively. 2) 12 age-matched children (7 girls and 5 boys) with unoperated submucous cleft palates. 3) 60 age-matched non-cleft children (30 girls and 30 boys) with normal occlusion. None of them received dentofacial orthopaedic treatment. While the patients who had been operated on had significant differences in posterior upper facial height and inclination of the palatal plane when compared with non-cleft children or unoperated cleft children, they showed no statistically significant difference in anteroposterior positioning of anterior part of the maxilla, compared with the unoperated. The influences of palatoplasty by the push-back procedure with posterior positioning of the palatal flaps on craniofacial morphology are additional to the cleft palate, and of minor concern. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  6. Sensitivity analysis of a validated subject-specific finite element model of the human craniofacial skeleton.

    Science.gov (United States)

    Szwedowski, T D; Fialkov, J; Whyne, C M

    2011-01-01

    Developing a more complete understanding of the mechanical response of the craniofacial skeleton (CFS) to physiological loads is fundamental to improving treatment for traumatic injuries, reconstruction due to neoplasia, and deformities. Characterization of the biomechanics of the CFS is challenging due to its highly complex structure and heterogeneity, motivating the utilization of experimentally validated computational models. As such, the objective of this study was to develop, experimentally validate, and parametrically analyse a patient-specific finite element (FE) model of the CFS to elucidate a better understanding of the factors that are of intrinsic importance to the skeletal structural behaviour of the human CFS. An FE model of a cadaveric craniofacial skeleton was created from subject-specific computed tomography data. The model was validated based on bone strain measurements taken under simulated physiological-like loading through the masseter and temporalis muscles (which are responsible for the majority of craniofacial physiologic loading due to mastication). The baseline subject-specific model using locally defined cortical bone thicknesses produced the strongest correlation to the experimental data (r2 = 0.73). Large effects on strain patterns arising from small parametric changes in cortical thickness suggest that the very thin bony structures present in the CFS are crucial to characterizing the local load distribution in the CFS accurately.

  7. Craniofacial Reconstruction by a Cost-Efficient Template-Based Process Using 3D Printing

    Directory of Open Access Journals (Sweden)

    Bilal Msallem, MD, DMD

    2017-11-01

    Full Text Available Summary:. Craniofacial defects often result in aesthetic and functional deficits, which affect the patient’s psyche and wellbeing. Patient-specific implants remain the optimal solution, but their use is limited or impractical due to their high costs. This article describes a fast and cost-efficient workflow of in-house manufactured patient-specific implants for craniofacial reconstruction and cranioplasty. As a proof of concept, we present a case of reconstruction of a craniofacial defect with involvement of the supraorbital rim. The following hybrid manufacturing process combines additive manufacturing with silicone molding and an intraoperative, manual fabrication process. A computer-aided design template is 3D printed from thermoplastics by a fused deposition modeling 3D printer and then silicone molded manually. After sterilization of the patient-specific mold, it is used intraoperatively to produce an implant from polymethylmethacrylate. Due to the combination of these 2 straightforward processes, the procedure can be kept very simple, and no advanced equipment is needed, resulting in minimal financial expenses. The whole fabrication of the mold is performed within approximately 2 hours depending on the template’s size and volume. This reliable technique is easy to adopt and suitable for every health facility, especially those with limited financial resources in less privileged countries, enabling many more patients to profit from patient-specific treatment.

  8. Availability of cosmetic treatment using novel cosmetics-based material on patients with craniofacial concavity.

    Science.gov (United States)

    Koyama, Shigeto; Kanetaka, Hiroyasu; Sagehashi, Yoshinori; Sasaki, Keiichi; Sato, Naoko

    2018-03-08

    Patients treated with maxillofacial prosthetics often experience emotional problems because of the remaining facial skin concavity such as a surgical scar. In such cases, cosmetic treatment can potentially correct their skin tone imperfections and deformities. This study aimed to evaluate the clinical availability of novel cosmetics-based material for craniofacial small concavity by initiating a cosmetic treatment in a preliminary case. Eighteen patients with aesthetic problems such as craniofacial deformities, small defects, and concavities on their faces underwent cosmetic treatment that was performed by makeup practitioners. Data were collected from the patient's charts and a survey questionnaire. A visual analog scale was used to conduct a survey regarding the satisfaction levels of the patients following cosmetic treatment with a novel cosmetics-based material. The cosmetic treatment was performed for a concavity on the left midface of a 67-year-old woman with partial maxillectomy. The novel cosmetics-based material was manufactured from a semi-translucent oil base. The satisfaction level of the patient increased after undergoing the cosmetic treatment. Regarding clinical applications, the novel cosmetics-based material can help reduce their cosmetic disturbance and restore the small deformity. These results suggest that the cosmetic treatment with the novel cosmetics-based material can be used as a subsidiary method for facial prostheses or an independent new method for correcting patients' small craniofacial concavity and for reducing visible deformity. Copyright © 2018 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  9. Lyophilized Platelet-Rich Fibrin (PRF Promotes Craniofacial Bone Regeneration through Runx2

    Directory of Open Access Journals (Sweden)

    Qi Li

    2014-05-01

    Full Text Available Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF. LPRF caused a 4.8-fold ± 0.4-fold elevation in Runt-related transcription factor 2 (Runx2 expression in alveolar bone cells, compared to a 3.6-fold ± 0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p < 0.001 when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

  10. Extract of mouse embryonic stem cells induces the expression of pluripotency genes in human adipose tissue-derived stem cells.

    Science.gov (United States)

    Salehi, Paria Motamen; Foroutan, Tahereh; Javeri, Arash; Taha, Masoumeh Fakhr

    2017-11-01

    In some previous studies, the extract of embryonic carcinoma cells (ECCs) and embryonic stem cells (ESCs) have been used to reprogram somatic cells to more dedifferentiated state. The aim of this study was to investigate the effect of mouse ESCs extract on the expression of some pluripotency markers in human adipose tissue-derived stem cells (ADSCs). Human ADSCs were isolated from subcutaneous abdominal adipose tissue and characterized by flow cytometric analysis for the expression of some mesenchymal stem cell markers and adipogenic and osteogenic differentiation. Frequent freeze-thaw technique was used to prepare cytoplasmic extract of ESCs. Plasma membranes of the ADSCs were reversibly permeabilized by streptolysin-O (SLO). Then the permeabilized ADSCs were incubated with the ESC extract and cultured in resealing medium. After reprogramming, the expression of some pluripotency genes was evaluated by RT-PCR and quantitative real-time PCR (qPCR) analyses. Third-passaged ADSCs showed a fibroblast-like morphology and expressed mesenchymal stem cell markers. They also showed adipogenic and osteogenic differentiation potential. QPCR analysis revealed a significant upregulation in the expression of some pluripotency genes including OCT4 , SOX2 , NANOG , REX1 and ESG1 in the reprogrammed ADSCs compared to the control group. These findings showed that mouse ESC extract can be used to induce reprogramming of human ADSCs. In fact, this method is applicable for reprogramming of human adult stem cells to a more pluripotent sate and may have a potential in regenerative medicine.

  11. Growth and morphogenesis of embryonic mouse organs on non-coated and extracellular matrix-coated Biopore membrane

    Science.gov (United States)

    Hardman, P.; Klement, B. J.; Spooner, B. S.

    1993-01-01

    Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.

  12. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  13. CNS embryonal tumours: WHO 2016 and beyond.

    Science.gov (United States)

    Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

    2018-02-01

    Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

  14. Transcriptional dynamics of a conserved gene expression network associated with craniofacial divergence in Arctic charr.

    Science.gov (United States)

    Ahi, Ehsan Pashay; Kapralova, Kalina Hristova; Pálsson, Arnar; Maier, Valerie Helene; Gudbrandsson, Jóhannes; Snorrason, Sigurdur S; Jónsson, Zophonías O; Franzdóttir, Sigrídur Rut

    2014-01-01

    Understanding the molecular basis of craniofacial variation can provide insights into key developmental mechanisms of adaptive changes and their role in trophic divergence and speciation. Arctic charr (Salvelinus alpinus) is a polymorphic fish species, and, in Lake Thingvallavatn in Iceland, four sympatric morphs have evolved distinct craniofacial structures. We conducted a gene expression study on candidates from a conserved gene coexpression network, focusing on the development of craniofacial elements in embryos of two contrasting Arctic charr morphotypes (benthic and limnetic). Four Arctic charr morphs were studied: one limnetic and two benthic morphs from Lake Thingvallavatn and a limnetic reference aquaculture morph. The presence of morphological differences at developmental stages before the onset of feeding was verified by morphometric analysis. Following up on our previous findings that Mmp2 and Sparc were differentially expressed between morphotypes, we identified a network of genes with conserved coexpression across diverse vertebrate species. A comparative expression study of candidates from this network in developing heads of the four Arctic charr morphs verified the coexpression relationship of these genes and revealed distinct transcriptional dynamics strongly correlated with contrasting craniofacial morphologies (benthic versus limnetic). A literature review and Gene Ontology analysis indicated that a significant proportion of the network genes play a role in extracellular matrix organization and skeletogenesis, and motif enrichment analysis of conserved noncoding regions of network candidates predicted a handful of transcription factors, including Ap1 and Ets2, as potential regulators of the gene network. The expression of Ets2 itself was also found to associate with network gene expression. Genes linked to glucocorticoid signalling were also studied, as both Mmp2 and Sparc are responsive to this pathway. Among those, several transcriptional

  15. Chromatin in embryonic stem cell neuronal differentiation.

    Science.gov (United States)

    Meshorer, E

    2007-03-01

    Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

  16. Three-dimensional epithelial tissues generated from human embryonic stem cells.

    Science.gov (United States)

    Hewitt, Kyle J; Shamis, Yulia; Carlson, Mark W; Aberdam, Edith; Aberdam, Daniel; Garlick, Jonathan A

    2009-11-01

    The use of pluripotent human embryonic stem (hES) cells for tissue engineering may provide advantages over traditional sources of progenitor cells because of their ability to give rise to multiple cell types and their unlimited expansion potential. We derived cell populations with properties of ectodermal and mesenchymal cells in two-dimensional culture and incorporated these divergent cell populations into three-dimensional (3D) epithelial tissues. When grown in specific media and substrate conditions, two-dimensional cultures were enriched in cells (EDK1) with mesenchymal morphology and surface markers. Cells with a distinct epithelial morphology (HDE1) that expressed cytokeratin 12 and beta-catenin at cell junctions became the predominant cell type when EDK1 were grown on surfaces enriched in keratinocyte-derived extracellular matrix proteins. When these cells were incorporated into the stromal and epithelial tissue compartments of 3D tissues, they generated multilayer epithelia similar to those generated with foreskin-derived epithelium and fibroblasts. Three-dimensional tissues demonstrated stromal cells with morphologic features of mature fibroblasts, type IV collagen deposition in the basement membrane, and a stratified epithelium that expressed cytokeratin 12. By deriving two distinct cell lineages from a common hES cell source to fabricate complex tissues, it is possible to explore environmental cues that will direct hES-derived cells toward optimal tissue form and function.

  17. Central nervous system mesenchymal chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F. [INM Neuromed IRCCS, Pozzilli (Italy). Dept. of Neurosurgery; Caroli, E. [Policlinico S. Andrea, Rome (Italy). Dept. of Neurological Sciences, Neurosurgery

    2005-06-15

    Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

  18. Central nervous system mesenchymal chondrosarcoma

    International Nuclear Information System (INIS)

    Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F.; Caroli, E.

    2005-01-01

    Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival

  19. Cleft Palate-Craniofacial Journal 50th anniversary editorial board commentary: anatomy, basic sciences, and genetics--then and now.

    Science.gov (United States)

    Mooney, Mark P; Cooper, Gregory M; Marazita, Mary L

    2014-05-01

    To celebrate the 50th year of the Cleft Palate-Craniofacial Journal we look back to where we started in 1964 and where we are now, and we speculate about directions for the future in a "Then and Now" editorial series. This editorial examines changing trends and perspectives in anatomical, basic science, and genetic studies published in this 50-year interval. In volume 1 there were 45 total papers, seven (16%) of which were peer-reviewed basic science and genetic articles published: four in anatomy, three in craniofacial biology, and none in genetics. In contrast, in volume 50, of 113 articles there were 47 (42%) peer-reviewed basic science and genetic articles published: 30 in anatomy, five in craniofacial biology, and 12 in genetics. Topical analysis of published manuscripts then and now reveal that similar topics in anatomy and craniofacial biology are still being researched today (e.g., phenotypic variability, optimal timing of surgery, presurgical orthopedics, bone grafting); whereas, most of the more recent papers use advanced technology to address old questions. In contrast, genetic publications have clearly increased in frequency during the last 50 years, which parallels advances in the field during this time. However, all of us have noticed that the more "cutting-edge" papers in these areas are not being submitted for publication to the journal, but instead to discipline-specific journals. Concerted efforts are therefore indicated to attract and publish these cutting-edge papers in order to keep the Cleft Palate-Craniofacial Journal in the forefront of orofacial cleft and craniofacial anomaly research and to provide a valuable service to American Cleft Palate-Craniofacial Association members.

  20. Relationships between craniocervical posture and pain-related disability in patients with cervico-craniofacial pain

    Directory of Open Access Journals (Sweden)

    López-de-Uralde-Villanueva I

    2015-07-01

    Full Text Available Ibai López-de-Uralde-Villanueva,1–4 Hector Beltran-Alacreu,1–3 Alba Paris-Alemany,1–4 Santiago Angulo-Díaz-Parreño,2,3,5 Roy La Touche1–4 1Department of Physiotherapy, Faculty of Health Science, 2Research Group on Movement and Behavioral Science and Study of Pain, The Center for Advanced Studies University La Salle, Universidad Autónoma de Madrid, Aravaca, Madrid, Spain; 3Institute of Neuroscience and Craniofacial Pain (INDCRAN, Madrid, Spain; 4Hospital La Paz Institute for Health Research, IdiPAZ, Madrid, Spain; 5Faculty of Medicine, Universidad San Pablo CEU, Madrid, Spain Objectives: This cross-sectional correlation study explored the relationships between craniocervical posture and pain-related disability in patients with chronic cervico-craniofacial pain (CCFP. Moreover, we investigated the test–retest intrarater reliability of two craniocervical posture measurements: head posture (HP and the sternomental distance (SMD. Methods: Fifty-three asymptomatic subjects and 60 CCFP patients were recruited. One rater measured HP and the SMD using a cervical range of motion device and a digital caliper, respectively. The Spanish versions of the neck disability index and the craniofacial pain and disability inventory were used to assess pain-related disability (neck disability and craniofacial disability, respectively. Results: We found no statistically significant correlations between craniocervical posture and pain-related disability variables (HP and neck disability [r=0.105; P>0.05]; HP and craniofacial disability [r=0.132; P>0.05]; SMD and neck disability [r=0.126; P>0.05]; SMD and craniofacial disability [r=0.195; P>0.05]. A moderate positive correlation was observed between HP and SMD for both groups (asymptomatic subjects, r=0.447; CCFP patients, r=0.52. Neck disability was strongly positively correlated with craniofacial disability (r=0.79; P>0.001. The test–retest intrarater reliability of the HP measurement was high for

  1. Properties of Dental Pulp-derived Mesenchymal Stem Cells and the Effects of Culture Conditions.

    Science.gov (United States)

    Kawashima, Nobuyuki; Noda, Sonoko; Yamamoto, Mioko; Okiji, Takashi

    2017-09-01

    Dental pulp mesenchymal stem cells (DPMSCs) highly express mesenchymal stem cell markers and possess the potential to differentiate into neural cells, osteoblasts, adipocytes, and chondrocytes. Thus, DPMSCs are considered suitable for tissue regeneration. The colony isolation method has commonly been used to collect relatively large amounts of heterogeneous DPMSCs. Homogenous DPMSCs can be isolated by fluorescence-activated cell sorting using antibodies against mesenchymal stem cell markers, although this method yields a limited number of cells. Both quality and quantity of DPMSCs are critical to regenerative therapy, and cell culture methods need to be improved. We thus investigated the properties of DPMSCs cultured with different methods. DPMSCs in a three-dimensional spheroid culture system, which is similar to the hanging drop culture for differentiation of embryonic stem cells, showed upregulation of odonto-/osteoblastic markers and mineralized nodule formation. This suggests that this three-dimensional spheroid culturing system for DPMSCs may be suitable for inducing hard tissues. We further examined the effect of cell culture density on the properties of DPMSCs because the properties of stem cells can be altered depending on the cell density. DPMSCs cultured under the confluent cell density condition showed slight downregulation of some mesenchymal stem cell markers compared with those under the sparse condition. The ability of DPMSCs to differentiate into hard tissue-forming cells was found to be enhanced in the confluent condition, suggesting that the confluent culture condition may not be suitable for maintaining the stemness of DPMSCs. When DPMSCs are to be used for hard tissue regeneration, dense followed by sparse cell culture conditions may be a better alternative strategy. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  2. In vitro differentiation of mouse embryonic stem cells into functional ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... hepatocyte transplantation therapy and toxicity screening in drug discovery. Key words: Embryonic stem cells, hepatic-like cells, in vitro differentiation, sodium butyrate, ... from embryonic stem (ES) cell or induced pluripotent.

  3. the production of mouse embryonic stem cells

    Indian Academy of Sciences (India)

    MADU

    What history tells us VII. Twenty-five years ago: the production of mouse embryonic stem cells ... cells into the cavity of the blastocyst, it will be possible to test the effect of .... to the use of efficient immunosuppressive drugs like cyclosporin – was ...

  4. How the embryonic chick brain twists.

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A

    2016-11-01

    During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left-right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left-right asymmetry in the early embryonic brain. © 2016 The Author(s).

  5. Embryonal rhabdomyosarcoma of the cervix | Ocheke | African ...

    African Journals Online (AJOL)

    Embryonal rhabdomyosarcoma (sarcoma botyroides) of the cervix, which is rare, is described in a 16-yearold. The combined use of chemotherapy, radiotherapy and surgery has markedly improved survival in those with this condition. However, our patient did not benefit from this treatment modality due to late presentation ...

  6. Embryonic Stem Cells and their Genetic Modification

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 2. Embryonic Stem Cells and their Genetic Modification - The Nobel Prize in Physiology or Medicine 2007. Mitradas M Panicker. General Article Volume 13 Issue 2 February 2008 pp 172-180 ...

  7. Transcriptome Landscapes of Mammalian Embryonic Cells

    NARCIS (Netherlands)

    Brinkhof, B.

    2015-01-01

    This thesis describes research on gene expression profiles from different embryonic stages and cell types to identify genes involved in pluripotency or differentiation in bovine and porcine cells. The results are compared with data from other mammals. RNA expression profiles of morula and blastocyst

  8. Morphometric analysis of craniofacial features in mono- and dizygotic twins discordant for unilateral cleft lip and palate.

    Science.gov (United States)

    Tessler, Alexis Y; Franchi, Lorenzo; McNamara, James A; Baccetti, Tiziano

    2011-09-01

    To compare craniofacial differences between twins discordant for surgically repaired unilateral cleft lip and palate (CLP) during the developmental ages and to test the effect of zygosity on the shape and size of the craniofacial skeleton of the same twins by means of thin plate spline (TPS) analysis. Lateral and posteroanterior (PA) cephalometric films from 19 sets of monozygotic (MZ) twins (15 male and 4 female) and 10 dizygotic (DZ) twins (7 male and 3 female) were analyzed. TPS analysis evaluated statistically significant differences in the craniofacial shape and size between affected and unaffected twins within MZ and DZ twin couples. No statistically significant differences in craniofacial shape or size between CLP and non-CLP MZ or DZ twins were observed. The level of morphological similarity in CLP vs non-CLP MZ twins was statistically greater than in DZ twins. Morphometric analysis showed that surgically repaired CLP does not produce significant shape or size differences in the craniofacial features of MZ or DZ twins discordant for unilateral CLP.

  9. Mesenchymal chondrosarcoma--a case report.

    Directory of Open Access Journals (Sweden)

    Tyagi S

    1992-01-01

    Full Text Available A Case of extraosseous mesenchymal chondrosarcoma occurring in the occipital region in a 26 year old male is being reported. The patient remained free from recurrence on any metastasis even after 2 years of the tumor resection.

  10. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

    Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

    2014-01-01

    Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue

  11. Mesenchymal stem cell therapy for laryngotracheal stenosis

    DEFF Research Database (Denmark)

    Jakobsen, Kathrine Kronberg; Grønhøj, Christian; Jensen, David H

    2017-01-01

    BACKGROUND: Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown...

  12. Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

    International Nuclear Information System (INIS)

    Kolesnichenko, T.S.; Gor'kova, T.G.

    1985-01-01

    Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

  13. Craniofacial morphology of Homo floresiensis: description, taxonomic affinities, and evolutionary implication.

    Science.gov (United States)

    Kaifu, Yousuke; Baba, Hisao; Sutikna, Thomas; Morwood, Michael J; Kubo, Daisuke; Saptomo, E Wahyu; Jatmiko; Awe, Rokhus Due; Djubiantono, Tony

    2011-12-01

    This paper describes in detail the external morphology of LB1/1, the nearly complete and only known cranium of Homo floresiensis. Comparisons were made with a large sample of early groups of the genus Homo to assess primitive, derived, and unique craniofacial traits of LB1 and discuss its evolution. Principal cranial shape differences between H. floresiensis and Homo sapiens are also explored metrically. The LB1 specimen exhibits a marked reductive trend in its facial skeleton, which is comparable to the H. sapiens condition and is probably associated with reduced masticatory stresses. However, LB1 is craniometrically different from H. sapiens showing an extremely small overall cranial size, and the combination of a primitive low and anteriorly narrow vault shape, a relatively prognathic face, a rounded oval foramen that is greatly separated anteriorly from the carotid canal/jugular foramen, and a unique, tall orbital shape. Whereas the neurocranium of LB1 is as small as that of some Homo habilis specimens, it exhibits laterally expanded parietals, a weak suprameatal crest, a moderately flexed occipital, a marked facial reduction, and many other derived features that characterize post-habilis Homo. Other craniofacial characteristics of LB1 include, for example, a relatively narrow frontal squama with flattened right and left sides, a marked frontal keel, posteriorly divergent temporal lines, a posteriorly flexed anteromedial corner of the mandibular fossa, a bulbous lateral end of the supraorbital torus, and a forward protruding maxillary body with a distinct infraorbital sulcus. LB1 is most similar to early Javanese Homo erectus from Sangiran and Trinil in these and other aspects. We conclude that the craniofacial morphology of LB1 is consistent with the hypothesis that H. floresiensis evolved from early Javanese H. erectus with dramatic island dwarfism. However, further field discoveries of early hominin skeletal remains from Flores and detailed analyses of the

  14. Psychometric evaluation of a motor control test battery of the craniofacial region.

    Science.gov (United States)

    von Piekartz, H; Stotz, E; Both, A; Bahn, G; Armijo-Olivo, S; Ballenberger, N

    2017-12-01

    The primary objective of this study was to determine the structural and known-group validity as well as the inter-rater reliability of a test battery to evaluate the motor control of the craniofacial region. Seventy volunteers without TMD and 25 subjects with TMD (Axes I) per the DC/TMD were asked to execute a test battery consisting of eight tests. The tests were video-taped in the same sequence in a standardised manner. Two experienced physical therapists participated in this study as blinded assessors. We used exploratory factor analysis to identify the underlying component structure of the eight tests. Internal consistency (Cronbach's α), inter-rater reliability (intra-class correlation coefficient) and construct validity (ie, hypothesis testing-known-group validity) (receiver operating curves) were also explored for the test battery. The structural validity showed the presence of one factor underlying the construct of the test battery. The internal consistency was excellent (0.90) as well as the inter-rater reliability. All values of reliability were close to 0.9 or above indicating very high inter-rater reliability. The area under the curve (AUC) was 0.93 for rater 1 and 0.94 for rater two, respectively, indicating excellent discrimination between subjects with TMD and healthy controls. The results of the present study support the psychometric properties of test battery to measure motor control of the craniofacial region when evaluated through videotaping. This test battery could be used to differentiate between healthy subjects and subjects with musculoskeletal impairments in the cervical and oro-facial regions. In addition, this test battery could be used to assess the effectiveness of management strategies in the craniofacial region. © 2017 John Wiley & Sons Ltd.

  15. The Art of Coping with a Craniofacial Difference: Helping Others through “Positive Exposure”

    Science.gov (United States)

    Loewenstein, Johanna; Sutton, Erica; Guidotti, Rick; Shapiro, Kristin; Ball, Karen; McLean, Diane; Biesecker, Barbara

    2011-01-01

    Finding ways to cope with social stigmatization is an important aspect of achieving adaptation for people living with visible genetic differences. This study describes the way individuals with craniofacial differences use an innovative photography and video experience with Positive Exposure (PE), a non-profit organization based in New York City, as a way to cope with their conditions. Thirty-five individuals between 12 and 61 years of age participated in this study. We administered surveys comprised of open-ended qualitative questions and quantitative measures designed to assess self-esteem, perceived stigma, and hopefulness. Data for this analysis was generated from the written questionnaires and interview transcripts. Most participants reported high levels of self-esteem and hopefulness, suggesting that they were relatively well adapted to their condition. Almost all participants described experiences of stigmatization throughout their lives. However, participants demonstrated their ability to implement a variety of coping strategies to manage stigma. ‘Helping others’ emerged as a prominent strategy among participants, aiding in the often lifelong process of adapting to their genetic difference. PE was described as an avenue through which participants could reach out to individuals and society at large, helping them adapt further to their condition. ‘Helping others’ may also benefit individuals with craniofacial differences who do not consider themselves to be well adapted to their condition. Health care providers can collaborate with PE, advocacy groups and other community or support groups to identify additional ways individuals with craniofacial differences can help themselves by reaching out to others. PMID:18478594

  16. Synchrotron Phase Tomography: An Emerging Imaging Method for Microvessel Detection in Engineered Bone of Craniofacial Districts

    Directory of Open Access Journals (Sweden)

    Alessandra Giuliani

    2017-09-01

    Full Text Available The engineering of large 3D constructs, such as certain craniofacial bone districts, is nowadays a critical challenge. Indeed, the amount of oxygen needed for cell survival is able to reach a maximum diffusion distance of ~150–200 μm from the original vascularization vector, often hampering the long-term survival of the regenerated tissues. Thus, the rapid growth of new blood vessels, delivering oxygen and nutrients also to the inner cells of the bone grafts, is mandatory for their long-term function in clinical practice. Unfortunately, significant progress in this direction is currently hindered by a lack of methods with which to visualize these processes in 3D and reliably quantify them. In this regard, a challenging method for simultaneous 3D imaging and analysis of microvascularization and bone microstructure has emerged in recent years: it is based on the use of synchrotron phase tomography. This technique is able to simultaneously identify multiple tissue features in a craniofacial bone site (e.g., the microvascular and the calcified tissue structure. Moreover, it overcomes the intrinsic limitations of both histology, achieving only a 2D characterization, and conventional tomographic approaches, poorly resolving the vascularization net in the case of an incomplete filling of the newly formed microvessels by contrast agents. Indeed, phase tomography, being based on phase differences among the scattered X-ray waves, is capable of discriminating tissues with similar absorption coefficients (like vessels and woven bone in defined experimental conditions. The approach reviewed here is based on the most recent experiences applied to bone regeneration in the craniofacial region.

  17. Investigation of an outbreak of craniofacial deformity in yellow-eyed penguin (Megadyptes antipodes) chicks.

    Science.gov (United States)

    Buckle, K N; Young, M J; Alley, M R

    2014-09-01

    To investigate an outbreak of severe craniofacial deformity in yellow-eyed penguin (Megadyptes antipodes, hōiho) chicks at a single breeding site on the Otago Peninsula in the South Island of New Zealand. Morbidity and mortality of yellow-eyed penguins breeding on the coastal regions of Otago was monitored from November 2008 to March 2009. Dead chicks and unhatched eggs were recovered and examined. Between October and December 2008 32 eggs were recorded at 17 nests in the Okia Reserve. Eleven chicks survived to about 90 days of age, of which eight were found to have moderate to severe craniofacial deformity. The six most severe chicks were subject to euthanasia and examined in detail at necropsy, and the remaining two affected chicks were released to the wild after a period of care in a rehabilitation centre. Post-mortem samples were analysed for inorganic and organic toxins. The six deformed chicks all had severe shortening of the mandible and maxilla by 20-50 mm. The rostral and caudal regions of the skull were approximately 40 and 80% of normal length, respectively. Other, more variable lesions included cross bill deformity, malformed bill keratin, microphthalmia with misshapen scleral ossicles and oral soft tissue excess thought to be secondary to bony malformations. During the same year, mild sporadic bill deformities were also reported in 10 unrelated chicks from >167 chicks at other breeding sites on the southern Otago coast. Concentrations of organic toxins and heavy metals in body tissues from affected chicks were apparently similar to those in unaffected chicks on other beaches. No cause of this outbreak of craniofacial deformity could be established although the high prevalence at a single site suggests that it was due to an unidentified local teratogen.

  18. Craniofacial reconstruction using patient-specific implants polyether ether ketone with computer-assisted planning.

    Science.gov (United States)

    Manrique, Oscar J; Lalezarzadeh, Frank; Dayan, Erez; Shin, Joseph; Buchbinder, Daniel; Smith, Mark

    2015-05-01

    Reconstruction of bony craniofacial defects requires precise understanding of the anatomic relationships. The ideal reconstructive technique should be fast as well as economical, with minimal donor-site morbidity, and provide a lasting and aesthetically pleasing result. There are some circumstances in which a patient's own tissue is not sufficient to reconstruct defects. The development of sophisticated software has facilitated the manufacturing of patient-specific implants (PSIs). The aim of this study was to analyze the utility of polyether ether ketone (PEEK) PSIs for craniofacial reconstruction. We performed a retrospective chart review from July 2009 to July 2013 in patients who underwent craniofacial reconstruction using PEEK-PSIs using a virtual process based on computer-aided design and computer-aided manufacturing. A total of 6 patients were identified. The mean age was 46 years (16-68 y). Operative indications included cancer (n = 4), congenital deformities (n = 1), and infection (n = 1). The mean surgical time was 3.7 hours and the mean hospital stay was 1.5 days. The mean surface area of the defect was 93.4 ± 43.26 cm(2), the mean implant cost was $8493 ± $837.95, and the mean time required to manufacture the implants was 2 weeks. No major or minor complications were seen during the 4-year follow-up. We found PEEK implants to be useful in the reconstruction of complex calvarial defects, demonstrating a low complication rate, good outcomes, and high patient satisfaction in this small series of patients. Polyether ether ketone implants show promising potential and warrant further study to better establish the role of this technology in cranial reconstruction.

  19. Effects of a child with a craniofacial anomaly on stability of the parental relationship.

    Science.gov (United States)

    St John, Dane; Pai, Lori; Belfer, Myron L; Mulliken, John B

    2003-09-01

    The purpose of this study was to determine rates of divorce in parents of children with various types of craniofacial anomalies and to analyze possible confounding factors. A 29-question survey was sent to parents of all children evaluated in the Craniofacial Centre between 1992 and 1997. Parents were questioned regarding pre- and postnatal marital stability, whether the child's facial anomaly contributed to divorce, and involvement in the child's welfare. Using deformational posterior plagiocephaly as a control group, rates of divorce vs. non-divorce were compared for craniofacial anomalies, categorized as asymmetric (hemifacial microsomia, unilateral coronal synostosis, cleft lip, cleft lip/palate) or symmetric (syndromic-craniosynostosis, orbital hypertelorism, Treacher Collins syndrome). Major anomalies (hemifacial microsomia, craniosynostosis, orbital hypertelorism, Treacher Collins syndrome) were also compared to minor anomalies (cleft lip, cleft lip/palate). Surveys were sent to both parents in 412 families; 403 surveys were returned; and the results were evaluated in 275 families (67%). Frequency analysis demonstrated an overall divorce rate of 6.8% and 4.9% separation. Anomalies associated with the highest rate of divorce were hemifacial microsomia (24.0%), syndromic craniosynostosis (12.2%), and cleft lip/palate (6.8%). 79% of non-divorced couples reported a strong prenatal relationship, whereas 59% of divorced couples reported a problematic relationship. Following birth of the affected child, 47% of non-divorced couples responded that the bonds became stronger and 41% of divorced couples thought the relationship worsened. Two-sided Fisher exact test comparing control vs. all other anomalies showed significance (p=.030) for rates of divorce. Separation of anomalies into asymmetric vs. symmetric and major vs. minor categories demonstrated no significant difference in divorce rate (p>.05). The mother was more likely to become a child's primary caregiver

  20. Identification of Isthmin 1 as a Novel Clefting and Craniofacial Patterning Gene in Humans.

    Science.gov (United States)

    Lansdon, Lisa A; Darbro, Benjamin W; Petrin, Aline L; Hulstrand, Alissa M; Standley, Jennifer M; Brouillette, Rachel B; Long, Abby; Mansilla, M Adela; Cornell, Robert A; Murray, Jeffrey C; Houston, Douglas W; Manak, J Robert

    2018-01-01

    Orofacial clefts are one of the most common birth defects, affecting 1-2 per 1000 births, and have a complex etiology. High-resolution array-based comparative genomic hybridization has increased the ability to detect copy number variants (CNVs) that can be causative for complex diseases such as cleft lip and/or palate. Utilizing this technique on 97 nonsyndromic cleft lip and palate cases and 43 cases with cleft palate only, we identified a heterozygous deletion of Isthmin 1 in one affected case, as well as a deletion in a second case that removes putative 3' regulatory information. Isthmin 1 is a strong candidate for clefting, as it is expressed in orofacial structures derived from the first branchial arch and is also in the same "synexpression group" as fibroblast growth factor 8 and sprouty RTK signaling antagonist 1a and 2 , all of which have been associated with clefting. CNVs affecting Isthmin 1 are exceedingly rare in control populations, and Isthmin 1 scores as a likely haploinsufficiency locus. Confirming its role in craniofacial development, knockdown or clustered randomly interspaced short palindromic repeats/Cas9-generated mutation of isthmin 1 in Xenopus laevis resulted in mild to severe craniofacial dysmorphologies, with several individuals presenting with median clefts. Moreover, knockdown of isthmin 1 produced decreased expression of LIM homeobox 8 , itself a gene associated with clefting, in regions of the face that pattern the maxilla. Our study demonstrates a successful pipeline from CNV identification of a candidate gene to functional validation in a vertebrate model system, and reveals Isthmin 1 as both a new human clefting locus as well as a key craniofacial patterning gene. Copyright © 2018 by the Genetics Society of America.

  1. Craniofacial structure variations in patients with palatal anomalies and velopharyngeal dysfunction.

    Science.gov (United States)

    Nachmani, Ariela; Aizenbud, Dror; Nageris, Ben; Emodi, Omri; Kassem, Firas

    2017-02-01

    Cephalometric evaluation of craniofacial and craniopharyngeal morphology is important for understanding the factors affecting velopharyngeal dysfunction (VPD) in patients with palatal anomalies. In this study, 366 patients with VPD were retrospectively stratified into cleft lip and palate (CLP), cleft palate (CP), submucous cleft palate (SMCP), occult submucous cleft palate (OSMCP), and non-CP groups. Lateral cephalometrics were used to assess craniofacial, craniopharyngeal, and velopharyngeal anatomy. The average craniofacial morphology in patients with VPD differed significantly according to the type of palatal anomaly. The non-CP and OSMCP groups differed from the CLP, CP, and SMCP groups in nasopharyngeal size and shape as depicted by a larger ANS-Ptm-Ve angle, a smaller S-N-Ba and NBa-PP angles, and a shorter linear value of S-Ar in the non-CP group. The CLP and CP groups had shorter ANS-Ptm, shorter Ptm-P, and smaller SNA and SNB angles. VPD patients with overt clefts have different skeletal and nasopharyngeal shapes compared to non-CP and OSMCP. Velopharyngeal function assessment should include the size and shape of the nasopharyngeal space in addition to the size and the activity of the velum and posterior and lateral walls of the nasopharynx. This should enable a more precise understanding of VPD pathology, and lead to improvements in the posterior pharyngeal flap technique in order to obtain better postoperative speech outcomes after surgical management of velopharyngeal dysfunction. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  2. Speech characteristics in a Ugandan child with a rare paramedian craniofacial cleft: a case report.

    Science.gov (United States)

    Van Lierde, K M; Bettens, K; Luyten, A; De Ley, S; Tungotyo, M; Balumukad, D; Galiwango, G; Bauters, W; Vermeersch, H; Hodges, A

    2013-03-01

    The purpose of this study is to describe the speech characteristics in an English-speaking Ugandan boy of 4.5 years who has a rare paramedian craniofacial cleft (unilateral lip, alveolar, palatal, nasal and maxillary cleft, and associated hypertelorism). Closure of the lip together with the closure of the hard and soft palate (one-stage palatal closure) was performed at the age of 5 months. Objective as well as subjective speech assessment techniques were used. The speech samples were perceptually judged for articulation, intelligibility and nasality. The Nasometer was used for the objective measurement of the nasalance values. The most striking communication problems in this child with the rare craniofacial cleft are an incomplete phonetic inventory, a severely impaired speech intelligibility with the presence of very severe hypernasality, mild nasal emission, phonetic disorders (omission of several consonants, decreased intraoral pressure in explosives, insufficient frication of fricatives and the use of a middorsum palatal stop) and phonological disorders (deletion of initial and final consonants and consonant clusters). The increased objective nasalance values are in agreement with the presence of the audible nasality disorders. The results revealed that several phonetic and phonological articulation disorders together with a decreased speech intelligibility and resonance disorders are present in the child with a rare craniofacial cleft. To what extent a secondary surgery for velopharyngeal insufficiency, combined with speech therapy, will improve speech intelligibility, articulation and resonance characteristics is a subject for further research. The results of such analyses may ultimately serve as a starting point for specific surgical and logopedic treatment that addresses the specific needs of children with rare facial clefts. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Semilongitudinal cephalometric study of craniofacial growth in untreated Class III malocclusion.

    Science.gov (United States)

    Alexander, Ann E Zionic; McNamara, James A; Franchi, Lorenzo; Baccetti, Tiziano

    2009-06-01

    Class III growth in white subjects is poorly characterized because of the low prevalence of the disharmony and the clinical tendency to treat this condition early. The purpose of this study was to investigate craniofacial growth changes by using longitudinal cephalometric records of white subjects with untreated Class III malocclusions to provide comparison data for studies of Class III treatment outcomes. Longitudinal records of 103 subjects were analyzed. Annual incremental growth changes in craniofacial variables from early childhood to late adolescence were examined for each sex. Inferential statistics were applied to changes in mandibular length, midfacial length, and lower anterior facial height of each sex (Wilcoxon tests) and between sexes (Mann-Whitney U tests). In the girls, the adolescent spurt in mandibular growth occurred between the ages of 10 and 12 years. In the boys, the adolescent mandibular growth spurt was between 12 and 15 years. Statistically significant growth changes in the average increments of growth of these linear measurements occurred in both sexes between 12 and 15 years. Adolescent peaks in midfacial growth were at prepubertal ages in both sexes. During childhood (5-7 years), much craniofacial growth occurred. Moreover, there was considerable mandibular growth relative to the maxilla in Class III subjects after the adolescent growth spurt. White Class III subjects showed definite worsening of the relative mandibular prognathism and sagittal skeletal discrepancy between the jaws with growth. The growth pattern of 3 fundamental cephalometric measurements (lower anterior face height, midfacial length, and mandibular length) exhibited differences between Class III male and female subjects in both the timing and the size of average growth increments in the adolescent growth spurt.

  4. The accuracy of a designed software for automated localization of craniofacial landmarks on CBCT images

    International Nuclear Information System (INIS)

    Shahidi, Shoaleh; Bahrampour, Ehsan; Soltanimehr, Elham; Zamani, Ali; Oshagh, Morteza; Moattari, Marzieh; Mehdizadeh, Alireza

    2014-01-01

    Two-dimensional projection radiographs have been traditionally considered the modality of choice for cephalometric analysis. To overcome the shortcomings of two-dimensional images, three-dimensional computed tomography (CT) has been used to evaluate craniofacial structures. However, manual landmark detection depends on medical expertise, and the process is time-consuming. The present study was designed to produce software capable of automated localization of craniofacial landmarks on cone beam (CB) CT images based on image registration and to evaluate its accuracy. The software was designed using MATLAB programming language. The technique was a combination of feature-based (principal axes registration) and voxel similarity-based methods for image registration. A total of 8 CBCT images were selected as our reference images for creating a head atlas. Then, 20 CBCT images were randomly selected as the test images for evaluating the method. Three experts twice located 14 landmarks in all 28 CBCT images during two examinations set 6 weeks apart. The differences in the distances of coordinates of each landmark on each image between manual and automated detection methods were calculated and reported as mean errors. The combined intraclass correlation coefficient for intraobserver reliability was 0.89 and for interobserver reliability 0.87 (95% confidence interval, 0.82 to 0.93). The mean errors of all 14 landmarks were <4 mm. Additionally, 63.57% of landmarks had a mean error of <3 mm compared with manual detection (gold standard method). The accuracy of our approach for automated localization of craniofacial landmarks, which was based on combining feature-based and voxel similarity-based methods for image registration, was acceptable. Nevertheless we recommend repetition of this study using other techniques, such as intensity-based methods

  5. Cervical vertebral column morphology related to craniofacial morphology and head posture in preorthodontic children with Class II malocclusion and horizontal maxillary overjet

    DEFF Research Database (Denmark)

    Arntsen, Torill; Sonnesen, Ane Liselotte

    2011-01-01

    In preorthodontic children with Class II malocclusion and horizontal maxillary overjet, cervical column morphology was examined and related to craniofacial morphology and head posture for the first time.......In preorthodontic children with Class II malocclusion and horizontal maxillary overjet, cervical column morphology was examined and related to craniofacial morphology and head posture for the first time....

  6. American Association of Orthodontists Foundation Craniofacial Growth Legacy Collection: Overview of a powerful tool for orthodontic research and teaching.

    Science.gov (United States)

    Baumrind, Sheldon; Curry, Sean

    2015-08-01

    This article reports on the current status of the American Association of Orthodontists Foundation (AAOF) Craniofacial Growth Legacy Collection--an AAOF-supported multi-institutional project that uses the Internet and cloud computing to collect and share craniofacial images and data for orthodontic research and education. The project gives investigators and clinicians all over the world online access to longitudinal information on craniofacial development in untreated children with malocclusions of various types. It also is a unique source of control samples for testing the validity of consensually accepted beliefs about the effects of orthodontic treatment or of failure to treat. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  7. Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

    Science.gov (United States)

    Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna

    2016-04-01

    Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  8. Common dental features and craniofacial development of three siblings with Ter Haar syndrome.

    Science.gov (United States)

    Parker, K; Pabla, R; Hay, N; Ayliffe, P

    2014-02-01

    Ter Haar syndrome is a rare genetic syndrome with <30 cases reported worldwide. There is nothing within the published literature regarding the dental development and dental features of these patients. This case series examines three patients with Ter Haar syndrome and tracks their dental development and identifies common dental and skeletal features. All three patients received dental treatment and regular follow-up at Great Ormond Street Hospital Dental Department. These patients have many common dental and craniofacial features which poses the question as to whether these features are due to Ter Haar syndrome.

  9. Craniofacial mucormycosis following assault: an unusual presentation of an unusual disease

    International Nuclear Information System (INIS)

    Melsom, S.M.; Khangure, M.S.

    2000-01-01

    A case of craniofacial mucormycosis following assault is discussed. A female diabetic developed peri-orbital cellulitis adjacent to a scalp wound which progressed to a necrotizing fasciitis. This did not respond to treatment. Subsequently the patient developed a hemiparesis, with CT imaging showing peri-orbital and paranasal sinus inflammatory changes, evidence of cavernous sinus invasion and development of a middle cerebral artery territory infarction. The patient died shortly afterwards. The imaging findings and their relationship to the pathological spread of mucor infection are discussed. Copyright (1999) Blackwell Science Pty Ltd

  10. Clinical Application of Three-Dimensional Printing Technology in Craniofacial Plastic Surgery

    OpenAIRE

    Choi, Jong Woo; Kim, Namkug

    2015-01-01

    Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to m...

  11. Craniofacial Statistical Deformation Models of Wild-type mice and Crouzon mice

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Ersbøll, Bjarne Kjær

    2007-01-01

    Crouzon syndrome is characterised by the premature fusion of cranial sutures and synchondroses leading to craniofacial growth disturbances. The gene causing the syndrome was discovered approximately a decade ago and recently the first mouse model of the syndrome was generated. In this study, a set...... of Micro CT scannings of the heads of wild-type (normal) mice and Crouzon mice were investigated. Statistical deformation models were built to assess the anatomical differences between the groups, as well as the within-group anatomical variation. Following the approach by Rueckert et al. we built an atlas...

  12. Distribution of epidermal growth factor receptors in rat tissues during embryonic skin development, hair formation, and the adult hair growth cycle

    DEFF Research Database (Denmark)

    Green, M R; Couchman, J R

    1984-01-01

    on the binding distribution of [125I]EGF, representing the tissue localization of available EGF receptors, during embryonic rat skin development including hair follicle formation and the adult hair growth cycle. At 16 days embryonic development a relatively low receptor density is seen over all the epidermal...... condensates marking the first stage of hair follicle development. This restricted and temporary loss of EGF receptors above these specialized mesenchymal condensates implies a role for the EGF receptor and possibly EGF or an EGF-like ligand in stimulating the epithelial downgrowth required for hair follicle...... development. In the anagen hair bulb, receptors for EGF are detected over the outer root sheath and the epithelial cell layers at the base of the follicle and show a correlation with the areas of epithelial proliferation in the hair bulb. During the catagen and telogen phases of the hair cycle, receptors...

  13. Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

    Science.gov (United States)

    Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

    2018-02-01

    Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

  14. Differential marker expression by cultures rich in mesenchymal stem cells

    Science.gov (United States)

    2013-01-01

    Background Mesenchymal stem cells have properties that make them amenable to therapeutic use. However, the acceptance of mesenchymal stem cells in clinical practice requires standardized techniques for their specific isolation. To date, there are no conclusive marker (s) for the exclusive isolation of mesenchymal stem cells. Our aim was to identify markers differentially expressed between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. We compared and contrasted the phenotype of tissue cultures in which mesenchymal stem cells are rich and rare. By initially assessing mesenchymal stem cell differentiation, we established that bone marrow and breast adipose cultures are rich in mesenchymal stem cells while, in our hands, foreskin fibroblast and olfactory tissue cultures contain rare mesenchymal stem cells. In particular, olfactory tissue cells represent non-stem cell mesenchymal cells. Subsequently, the phenotype of the tissue cultures were thoroughly assessed using immuno-fluorescence, flow-cytometry, proteomics, antibody arrays and qPCR. Results Our analysis revealed that all tissue cultures, regardless of differentiation potential, demonstrated remarkably similar phenotypes. Importantly, it was also observed that common mesenchymal stem cell markers, and fibroblast-associated markers, do not discriminate between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. Examination and comparison of the phenotypes of mesenchymal stem cell and non-stem cell mesenchymal cell cultures revealed three differentially expressed markers – CD24, CD108 and CD40. Conclusion We indicate the importance of establishing differential marker expression between mesenchymal stem cells and non-stem cell mesenchymal cells in order to determine stem cell specific markers. PMID:24304471

  15. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2005-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  16. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2003-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  17. Embryonic vaccines against cancer: an early history.

    Science.gov (United States)

    Brewer, Bradley G; Mitchell, Robert A; Harandi, Amir; Eaton, John W

    2009-06-01

    Almost 100 years have passed since the seminal observations of Schöne showing that vaccination of animals with fetal tissue would prevent the growth of transplantable tumors. Many subsequent reports have affirmed the general idea that immunologic rejection of transplantable tumors, as well as prevention of carcinogenesis, may be affected by vaccination with embryonic/fetal material. Following a decade of intense research on this phenomenon during approximately 1964-1974, interest appears to have waned. This earlier experimental work may be particularly pertinent in view of the rising interest in so-called cancer stem cells. We believe that further work - perhaps involving the use of embryonic stem cells as immunogens - is warranted and that the results reviewed herein support the concept that vaccination against the appearance of cancers of all kinds is a real possibility.

  18. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  19. Hedgehog Signalling in the Embryonic Mouse Thymus

    Directory of Open Access Journals (Sweden)

    Alessandro Barbarulo

    2016-07-01

    Full Text Available T cells develop in the thymus, which provides an essential environment for T cell fate specification, and for the differentiation of multipotent progenitor cells into major histocompatibility complex (MHC-restricted, non-autoreactive T cells. Here we review the role of the Hedgehog signalling pathway in T cell development, thymic epithelial cell (TEC development, and thymocyte–TEC cross-talk in the embryonic mouse thymus during the last week of gestation.

  20. Ear embryonic rabdomiosarcoma. A case report

    International Nuclear Information System (INIS)

    Cueto, L.; Canabal, A.; Blanco, A.; Sabate, J.

    2002-01-01

    A case of embryonic rabdomiosarcoma in the ear of a 5-year-old girl who initially shows clinical symptoms of otitis media. The CT reveals a dense lesion of soft tissue which shows up slightly in the right external auditory channel. Also of interest were osteolytic areas in the petrous, clivus and zygomatic arch. A hypointensive lesion with marked enhancement after Gd-DPTA injection is observed. Discussed are the imaging methods used in the diagnosis of this tumor. (Author) 10 refs

  1. The Use of Embryonic Stem Cells

    OpenAIRE

    Corkery, Padraig

    2002-01-01

    Over the past year there has been great interest, optimism and anxiety in many societies about developments in the use of embryonic stem cells (ES cells). Within the scientific community there has been debate for some time on the merits and ethical implications of using ES cells. The discussion entered the public domain inthe decisive way during the past year when there were significant changes in legislation governing the use of such cells in Britain and the United States. These changes c...

  2. Regulation of Pituitary Stem Cells by Epithelial to Mesenchymal Transition Events and Signaling Pathways

    Science.gov (United States)

    Cheung, Leonard Y. M.; Davis, Shannon W.; Brinkmeier, Michelle L.; Camper, Sally A.; Pérez-Millán, María Inés

    2017-01-01

    The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. The adult anterior pituitary responds to physiological challenge by mobilizing the SOX2-expressing progenitor pool and producing additional hormone-producing cells. Knowledge of the role of signaling pathways and extracellular matrix components in these processes may lead to improvements in the efficiency of differentiation of embryonic stem cells or induced pluripotent stem cells into hormone producing cells in vitro. Advances in our basic understanding of pituitary stem cell regulation and differentiation may lead to improved diagnosis and treatment for patients with hypopituitarism. PMID:27650955

  3. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  4. Mesenchymal Stem Cells as a Potent Cell Source for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Elham Zomorodian

    2012-01-01

    Full Text Available While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs, adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs, as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.

  5. Do embryonic polar bodies commit suicide?

    Science.gov (United States)

    Fabian, Dušan; Čikoš, Štefan; Rehák, Pavol; Koppel, Juraj

    2014-02-01

    The extrusion and elimination of unnecessary gametic/embryonic material is one of the key events that determines the success of further development in all living organisms. Oocytes produce the first polar body to fulfill the maturation process just before ovulation, and release the second polar body immediately after fertilization. The aim of this study was to compile a physiological overview of elimination of polar bodies during early preimplantation development in mice. Our results show that three-quarters of the first polar bodies were lost even at the zygotic stage; the 4-cell stage embryos contained only one (second) polar body, and the elimination of second polar bodies proceeded continuously during later development. Both first and second polar bodies showed several typical features of apoptosis: phosphatidylserine redistribution (observed for the first time in the first polar body), specific DNA degradation, condensed nuclear morphology, and inability to exclude cationic dye from the nucleus during the terminal stage of the apoptotic process. Caspase-3 activity was recorded only in the second polar body. From the morphological point of view, mouse polar bodies acted very similarly to damaged embryonic cells which have lost contact with their neighboring blastomeres. In conclusion, polar bodies possess all the molecular equipment necessary for triggering and executing an active suicide process. Furthermore, similarly as in dying embryonic cells, stressing external conditions (culture in vitro) might accelerate and increase the incidence of apoptotic elimination of the polar bodies in embryos.

  6. Mechanical signaling coordinates the embryonic heartbeat

    Science.gov (United States)

    Chiou, Kevin K.; Rocks, Jason W.; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E.; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F.; Prosser, Benjamin L.; Discher, Dennis E.; Liu, Andrea J.

    2016-01-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts—consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  7. Geometric morphometrics in primatology: craniofacial variation in Homo sapiens and Pan troglodytes.

    Science.gov (United States)

    Lynch, J M; Wood, C G; Luboga, S A

    1996-01-01

    Traditionally, morphometric studies have relied on statistical analysis of distances, angles or ratios to investigate morphometric variation among taxa. Recently, geometric techniques have been developed for the direct analysis of landmark data. In this paper, we offer a summary (with examples) of three of these newer techniques, namely shape coordinate, thin-plate spline and relative warp analyses. Shape coordinate analysis detected significant craniofacial variation between 4 modern human populations, with African and Australian Aboriginal specimens being relatively prognathous compared with their Eurasian counterparts. In addition, the Australian specimens exhibited greater basicranial flexion than all other samples. The observed relationships between size and craniofacial shape were weak. The decomposition of shape variation into affine and non-affine components is illustrated via a thin-plate spline analysis of Homo and Pan cranial landmarks. We note differences between Homo and Pan in the degree of prognathism and basicranial flexion and the position and orientation of the foramen magnum. We compare these results with previous studies of these features in higher primates and discuss the utility of geometric morphometrics as a tool in primatology and physical anthropology. We conclude that many studies of morphological variation, both within and between taxa, would benefit from the graphical nature of these techniques.

  8. Craniofacial morphology in children with van der Woude syndrome and isolated cleft palate.

    Science.gov (United States)

    Heliövaara, Arja; Karhulahti, Rekina; Rautio, Jorma

    2015-01-01

    To compare cephalometrically 6-year-old children with van der Woude syndrome and cleft palate (VWS) to children with isolated cleft palate alone (CP). A retrospective case-control study. Forty-four children with VWS were compared to 73 children with CP using lateral cephalograms. The mean age of the children with VWS was 6.6 years (range = 5.9-8.2) and that of the children with CP, 6.2 years (range = 5.7-6.7). Palatal closure had been done at a mean age of 1.4 years (range = 0.8-2.2), mostly with the Veau-Wardill-Killner or the Cronin pushback surgical techniques. The data was collected over a 30-year period. Linear and angular measurements were obtained from lateral cephalograms. A Student's t-test was used in the statistical analysis. The craniofacial morphology in children with VWS and CP was similar, but those with VWS had slightly smaller diameters of the lower pharyngeal airway. The maxilla and mandible were well related to each other, although a little retrusive in relation to the cranial base. The soft tissue profile reflected the skeletal relationships, no significant protrusion of the lower lip was noted. Six-year-old children with VWS and CP have similar craniofacial morphology.

  9. Sagittal and Vertical Craniofacial Growth Pattern and Timing of Circumpubertal Skeletal Maturation: A Multiple Regression Study

    Directory of Open Access Journals (Sweden)

    Giuseppe Perinetti

    2016-01-01

    Full Text Available The knowledge of the associations between the timing of skeletal maturation and craniofacial growth is of primary importance when planning a functional treatment for most of the skeletal malocclusions. This cross-sectional study was thus aimed at evaluating whether sagittal and vertical craniofacial growth has an association with the timing of circumpubertal skeletal maturation. A total of 320 subjects (160 females and 160 males were included in the study (mean age, 12.3±1.7 years; range, 7.6–16.7 years. These subjects were equally distributed in the circumpubertal cervical vertebral maturation (CVM stages 2 to 5. Each CVM stage group also had equal number of females and males. Multiple regression models were run for each CVM stage group to assess the significance of the association of cephalometric parameters (ANB, SN/MP, and NSBa angles with age of attainment of the corresponding CVM stage (in months. Significant associations were seen only for stage 3, where the SN/MP angle was negatively associated with age (β coefficient, −0.7. These results show that hyperdivergent and hypodivergent subjects may have an anticipated and delayed attainment of the pubertal CVM stage 3, respectively. However, such association remains of little entity and it would become clinically relevant only in extreme cases.

  10. Pedicled Temporalis Muscle Flap for Craniofacial Reconstruction: A 35-Year Clinical Experience with 366 Flaps.

    Science.gov (United States)

    Spanio di Spilimbergo, Stefano; Nordera, Paolo; Mardini, Samir; Castiglione, Giusy; Chim, Harvey; Pinna, Vittore; Brunello, Massimo; Cusino, Claudio; Roberto, Squaquara; Baciliero, Ugo

    2017-02-01

    In the past 130 years, the temporalis muscle flap has been used for a variety of different indications. In this age of microsurgery and perforator flaps, the temporalis muscle flap still has many useful applications for craniofacial reconstruction. Three hundred sixty-six temporalis muscle flaps were performed in a single center between 1978 and 2012. The authors divided the cases into two series-before and after 1994-because, after 1994, they started to perform free flap reconstructions, and indications for reconstruction with a temporalis muscle flap were changed RESULTS:: In the series after 1994, flaps were most commonly used for reconstruction of defects in the maxilla, mandible, and oropharynx, in addition to facial reanimation and filling of orbital defects. Complications included total flap necrosis (1.6 percent) and partial flap necrosis (10.7 percent). The rate of material extrusion at the donor site decreased after porous polyethylene was uniformly used for reconstruction from 17.1 to 7.9 percent. The pedicled temporalis muscle flap continues to have many applications in craniofacial reconstruction. With increasing use of free flaps, the authors' indications for the pedicled temporalis muscle flap are now restricted to (1) orbital filling for congenital or acquired anophthalmia; (2) filling of unilateral maxillectomy defects; and (3) facial reanimation in selected cases of facial nerve palsy. Therapeutic, IV.

  11. A comparative study of craniofacial morphology of cleft lip children with or without palate

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Su Beom; Kim, Young Ju; Koh, Kwang Joon [Dept. of Oral Radiology, College of Dentistry, Chonbuk National University, Chonju (Korea, Republic of)

    1995-08-15

    The purpose of this study was to determine whether any difference existed in craniofacial morphology between cleft children and normal subjects. Thirty three measurements of the various regions of cranium and face were obtained from lateral cephalometric radiograms in 40 cleft children (27 males, 13 females) and 40 normal subjects (23 males, 17 females) in our dental hospital from Jan. 1988 to Dec. 1995. The measurements were compared with those in control subjects who had no history of craniofacial abnormalities.. The obtained results were as follows; l. In the cranium, the cleft children had significantly shorter posterior cranial base length (S-Ba) and total antero-posterior cranial base length (N-Ba) (P<0.05). 2. In the upper face, the cleft children had significantly shorter upper anterior facial height (N-ANS) and upper posterior facial height (Ptm'-SNL) (P<0.05). 3. In the lower face, the cleft children had significantly shorter antero-posterior mandibular length (Pog-Ar) and antero-posterior mandibular body length (Pog-Go) (P<0.05). 4. In the facial profile, the cleft children had significantly shorter total facial height (N-Me) and posterior facial height (S-Go) (P<0.05).

  12. Thin-plate spline analysis of craniofacial morphology in subjects with adenoid or tonsillar hypertrophy.

    Science.gov (United States)

    Baroni, Michela; Ballanti, Fabiana; Polimeni, Antonella; Franchi, Lorenzo; Cozza, Paola

    2011-04-01

    To compare the skeletal features of subjects with adenoid hypertrophy with those of children with tonsillar hypertrophy using thin-plate spline (TPS) analysis. A group of 20 subjects (9 girls and 11 boys; mean age 8.4 ± 0.9 years) with adenoid hypertrophy (AG) was compared with a group of 20 subjects (10 girls and 10 boys; mean age 8.2 ± 1.1 years) with tonsillar hypertrophy (TG). Craniofacial morphology was analyzed on the lateral cephalograms of the subjects in both groups by means of TPS analysis. A cross-sectional comparison was performed on both size and shape differences between the two groups. AG exhibited statistically significant shape and size differences in craniofacial configuration with respect to TG. Subjects with adenoid hypertrophy showed an upward dislocation of the anterior region of the maxilla, a more downward/backward position of the anterior region of the mandibular body and an upward/backward displacement of the condylar region. Conversely, subjects with tonsillar hypertrophy showed a downward dislocation of the anterior region of the maxilla, a more upward/forward position of the anterior region of the mandibular body and a downward/forward displacement of the condylar region. Subjects with adenoid hypertrophy exhibited features suggesting a more retrognathic mandible while subjects with tonsillar hypertrophy showed features suggesting a more prognathic mandible. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. CT interpretation of craniofacial anomalies: a comparative analysis by undergraduate dental students

    International Nuclear Information System (INIS)

    Gaia, Bruno Felipe; Perella, Andreia; Cara, Ana Claudia Ballet de; Antunes, Jose Leopoldo Ferreira; Cavalcanti, Marcelo Gusmao Paraiso

    2005-01-01

    The aim of this study was to evaluate the accuracy and reproducibility of computed tomography (CT) image interpretation made in axial slices (2D-CT) and 3D reconstructed images (3D-CT) of patients with craniofacial anomalies. The analyses were made by undergraduate dental students, and compared with the diagnoses considered upon surgical intervention. Computed tomography of 43 patients were analyzed independently by three calibrated examiners (undergraduate students) with, respectively, one, two, and three semesters of experience in craniofacial CT training and interpretation. The analysis of 2D-CT and 3D-CT images were performed at distinct times using an independent workstation associated with a specific computer graphics software for volumetric images. The analysis of inter-examiner agreement and of the agreement between observers and the gold standard was performed using the Kappa test. The accuracy evaluation presented a progressively higher value for examiners with progressively broader experience in 2D-CT and 3D-CT image interpretation. 3D-CT analyses allowed a higher inter-examiner agreement (1 - 0.896) than 2D-CT analyses (1 - 0.614). 3D-CT was considered more precise and accurate than 2D-CT for all students' evaluations. The reproducibility and accuracy varied according to the experience in CT interpretation, and the most experienced student achieved results closer to the gold standard. (author)

  14. Lyophilized platelet-rich fibrin (PRF) promotes craniofacial bone regeneration through Runx2.

    Science.gov (United States)

    Li, Qi; Reed, David A; Min, Liu; Gopinathan, Gokul; Li, Steve; Dangaria, Smit J; Li, Leo; Geng, Yajun; Galang, Maria-Therese; Gajendrareddy, Praveen; Zhou, Yanmin; Luan, Xianghong; Diekwisch, Thomas G H

    2014-05-14

    Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold±0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold±0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (pfibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

  15. Dental and craniofacial characteristics in a patient with Dubowitz syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Tullo Domenica

    2011-01-01

    Full Text Available Abstract Introduction Dubowitz syndrome is a very rare, autosomal recessive disease characterized by microcephaly, growth retardation, a high sloping forehead, facial asymmetry, blepharophimosis, sparse hair and eyebrows, low-set ears and mental retardation. Symptoms vary between patients, but other characteristics include a soft high-pitched voice, dental and craniofacial abnormalities, partial webbing of the fingers and toes, palate deformations, genital abnormalities, eczema, hyperactivity, preference for concrete over abstract thinking, language difficulties and an aversion to crowds. Case presentation We describe the craniofacial and dental characteristics of a 12-year-old Caucasian Italian boy with both the typical and less common findings of Dubowitz syndrome. Conclusion Diagnosis of Dubowitz syndrome is mainly based on the facial phenotype. Possible conditions for differential diagnosis include Bloom syndrome, Smith-Lemli-Opitz syndrome, and fetal alcohol syndrome. As there are few reports of this syndrome in the literature, we hope this case report will enable health professionals to recognize the phenotypic alterations of this syndrome, and allow early referral for the necessary multidisciplinary treatments.

  16. Emotional and behavioral reactions to facially deformed patients before and after craniofacial surgery.

    Science.gov (United States)

    Barden, R C; Ford, M E; Wilhelm, W M; Rogers-Salyer, M; Salyer, K E

    1988-09-01

    The present experiment investigated whether observers' emotional and behavioral reactions to facially deformed patients could be substantially improved by surgical procedures conducted by well-trained specialists in an experienced multidisciplinary team. Also investigated was the hypothesis that emotional states mediate the effects of physical attractiveness and facial deformity on social interaction. Twenty patients between the ages of 3 months and 17 years were randomly selected from over 2000 patients' files of Kenneth E. Salyer of Dallas, Texas. Patient diagnoses included facial clefts, hypertelorism, Treacher Collins syndrome, and craniofacial dysostoses (Crouzon's and Apert's syndromes). Rigorously standardized photographs of patients taken before and after surgery were shown to 22 "naive" raters ranging in age from 18 to 54 years. Raters were asked to predict their emotional and behavioral responses to the patients. These ratings indicated that observers' behavioral reactions to facially deformed children and adolescents would be more positive following craniofacial surgery. Similarly, the ratings indicated that observers' emotional reactions to these patients would be more positive following surgery. The results are discussed in terms of current sociopsychologic theoretical models for the effects of attractiveness on social interaction. A new model is presented that implicates induced emotional states as a mediating process in explaining the effects of attractiveness and facial deformity on the quality of social interactions. Limitations of the current investigation and directions for future research are also discussed.

  17. pitx2 Deficiency results in abnormal ocular and craniofacial development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Yi Liu

    Full Text Available Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2(ex4/5 splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition helix of the DNA-binding homeodomain. The morphological phenotype of pitx2(ex4/5 morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6-8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2(ex4/5 morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates.

  18. A three-dimensional comparison of a morphometric and conventional cephalometric midsagittal planes for craniofacial asymmetry.

    Science.gov (United States)

    Damstra, Janalt; Fourie, Zacharias; De Wit, Marnix; Ren, Yijin

    2012-02-01

    Morphometric methods are used in biology to study object symmetry in living organisms and to determine the true plane of symmetry. The aim of this study was to determine if there are clinical differences between three-dimensional (3D) cephalometric midsagittal planes used to describe craniofacial asymmetry and a true symmetry plane derived from a morphometric method based on visible facial features. The sample consisted of 14 dry skulls (9 symmetric and 5 asymmetric) with metallic markers which were imaged with cone-beam computed tomography. An error study and statistical analysis were performed to validate the morphometric method. The morphometric and conventional cephalometric planes were constructed and compared. The 3D cephalometric planes constructed as perpendiculars to the Frankfort horizontal plane resembled the morphometric plane the most in both the symmetric and asymmetric groups with mean differences of less than 1.00 mm for most variables. However, the standard deviations were often large and clinically significant for these variables. There were clinically relevant differences (>1.00 mm) between the different 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features. The difference between 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features were clinically relevant. Care has to be taken using cephalometric midsagittal planes for diagnosis and treatment planning of craniofacial asymmetry as they might differ from the true plane of symmetry as determined by morphometrics.

  19. Dental and craniofacial characteristics in a patient with Dubowitz syndrome: a case report.

    Science.gov (United States)

    Ballini, Andrea; Cantore, Stefania; Tullo, Domenica; Desiate, Apollonia

    2011-01-27

    Dubowitz syndrome is a very rare, autosomal recessive disease characterized by microcephaly, growth retardation, a high sloping forehead, facial asymmetry, blepharophimosis, sparse hair and eyebrows, low-set ears and mental retardation. Symptoms vary between patients, but other characteristics include a soft high-pitched voice, dental and craniofacial abnormalities, partial webbing of the fingers and toes, palate deformations, genital abnormalities, eczema, hyperactivity, preference for concrete over abstract thinking, language difficulties and an aversion to crowds. We describe the craniofacial and dental characteristics of a 12-year-old Caucasian Italian boy with both the typical and less common findings of Dubowitz syndrome. Diagnosis of Dubowitz syndrome is mainly based on the facial phenotype. Possible conditions for differential diagnosis include Bloom syndrome, Smith-Lemli-Opitz syndrome, and fetal alcohol syndrome. As there are few reports of this syndrome in the literature, we hope this case report will enable health professionals to recognize the phenotypic alterations of this syndrome, and allow early referral for the necessary multidisciplinary treatments.

  20. A comparative study of craniofacial morphology of cleft lip children with or without palate

    International Nuclear Information System (INIS)

    Cho, Su Beom; Kim, Young Ju; Koh, Kwang Joon

    1995-01-01

    The purpose of this study was to determine whether any difference existed in craniofacial morphology between cleft children and normal subjects. Thirty three measurements of the various regions of cranium and face were obtained from lateral cephalometric radiograms in 40 cleft children (27 males, 13 females) and 40 normal subjects (23 males, 17 females) in our dental hospital from Jan. 1988 to Dec. 1995. The measurements were compared with those in control subjects who had no history of craniofacial abnormalities.. The obtained results were as follows; l. In the cranium, the cleft children had significantly shorter posterior cranial base length (S-Ba) and total antero-posterior cranial base length (N-Ba) (P<0.05). 2. In the upper face, the cleft children had significantly shorter upper anterior facial height (N-ANS) and upper posterior facial height (Ptm'-SNL) (P<0.05). 3. In the lower face, the cleft children had significantly shorter antero-posterior mandibular length (Pog-Ar) and antero-posterior mandibular body length (Pog-Go) (P<0.05). 4. In the facial profile, the cleft children had significantly shorter total facial height (N-Me) and posterior facial height (S-Go) (P<0.05).

  1. Sagittal and Vertical Craniofacial Growth Pattern and Timing of Circumpubertal Skeletal Maturation: A Multiple Regression Study

    Science.gov (United States)

    Rosso, Luigi; Riatti, Riccardo

    2016-01-01

    The knowledge of the associations between the timing of skeletal maturation and craniofacial growth is of primary importance when planning a functional treatment for most of the skeletal malocclusions. This cross-sectional study was thus aimed at evaluating whether sagittal and vertical craniofacial growth has an association with the timing of circumpubertal skeletal maturation. A total of 320 subjects (160 females and 160 males) were included in the study (mean age, 12.3 ± 1.7 years; range, 7.6–16.7 years). These subjects were equally distributed in the circumpubertal cervical vertebral maturation (CVM) stages 2 to 5. Each CVM stage group also had equal number of females and males. Multiple regression models were run for each CVM stage group to assess the significance of the association of cephalometric parameters (ANB, SN/MP, and NSBa angles) with age of attainment of the corresponding CVM stage (in months). Significant associations were seen only for stage 3, where the SN/MP angle was negatively associated with age (β coefficient, −0.7). These results show that hyperdivergent and hypodivergent subjects may have an anticipated and delayed attainment of the pubertal CVM stage 3, respectively. However, such association remains of little entity and it would become clinically relevant only in extreme cases. PMID:27995136

  2. Local myogenic pulp-derived cell injection enhances craniofacial muscle regeneration in vivo.

    Science.gov (United States)

    Jung, J E; Song, M J; Shin, S; Choi, Y J; Kim, K H; Chung, C J

    2017-02-01

    To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5-aza-2'-deoxycytidine (5-Aza), and to evaluate the potent stimulatory effect of 5-Aza-treated pulp cell injection for craniofacial muscle regeneration in vivo. Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18-22.1 years). Levels of myogenic differentiation and functional contraction response in vitro were compared between pulp cells with or without pre-treatment of 5-Aza. Changes in muscle regeneration in response to green fluorescent protein (GFP)-labelled myogenic pulp cell injection in vivo were evaluated using a cardiotoxin (CTX)-induced muscle injury model of the gastrocnemius as well as the masseter muscle in mice. Pre-treatment of 5-Aza in pulp cells stimulated myotube formation, myogenic differentiation in terms of desmin and myogenin expression, and the level of collagen gel contraction. The local injection of 5-Aza pre-treated myogenic pulp cells was engrafted into the host tissue and indicated signs of enhanced muscle regeneration in both the gastrocnemius and the masseter muscles. The epigenetic modification of pulp cells from extracted premolars and the local injection of myogenic pulp cells may stimulate craniofacial muscles regeneration in vivo. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Possible mechanism of disintegrin/like domain in mesenchymal ...

    African Journals Online (AJOL)

    Possible mechanism of disintegrin/like domain in mesenchymal stem cells homing in mice liver injury ... PROMOTING ACCESS TO AFRICAN RESEARCH ... Mesenchymal Stem cells have opened a new approach to deal with liver fibrosis.

  4. Defining the expression of marker genes in equine mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Deborah J Guest

    2008-11-01

    Full Text Available Deborah J Guest1, Jennifer C Ousey1, Matthew RW Smith21Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU; 2Reynolds House Referrals, Greenwood Ellis and Partners, 166 High Street, Newmarket, Suffolk, CB8 9WS, UKAbstract: Mesenchymal stromal (MS cells have been derived from multiple sources in the horse including bone marrow, adipose tissue and umbilical cord blood. To date these cells have been investigated for their differentiation potential and are currently being used to treat damage to horse musculoskeletal tissues. However, no work has been done in horse MS cells to examine the expression profile of proteins and cell surface antigens that are expressed in human MS cells. The identification of such profiles in the horse will allow the comparison of putative MS cells isolated from different laboratories and different tissues. At present it is difficult to ascertain whether equivalent cells are being used in different reports. Here, we report on the expression of a range of markers used to define human MS cells. Using immunocytochemistry we show that horse MS cells homogenously express collagens, alkaline phosphatase activity, CD44, CD90 and CD29. In contrast, CD14, CD79α and the embryonic stem cell markers Oct-4, SSEA (stage specific embryonic antigen -1, -3, -4, TRA (tumor rejection antigen -1–60 and -1–81 are not expressed. The MS cells also express MHC class I antigens but do not express class II antigens, although they are inducible by treatment with interferon gamma (IFN-γ.Keywords: mesenchymal stem cells, equine, gene expression

  5. Premature birth--Studies on orthodontic treatment need, craniofacial morphology and function.

    Science.gov (United States)

    Paulsson, Liselotte

    2009-01-01

    A series of studies have been initiated implying a unique opportunity to evaluate and compare malocclusion traits, orthodontic treatment need, craniofacial morphology, mandibular function, signs and symptoms of temporomandibular disorders (TMD) and headache between extremely preterm (EPT; born before the 29th week of gestation) and very preterm (VPT; born between 29 and 32 weeks of gestation) and full-term born children. THIS THESIS WAS BASED ON FOUR STUDIES: Paper I. A systematic literature review was undertaken to answer the following questions: Does prematurity result in alterations of palatal morphology, dental occlusion, tooth-crown dimensions, tooth maturation and eruption? What role does neonatal oral intubation play in the appearance of the alterations? Are the alterations in morphology permanent or transient? The literature search spanned from January 1966 to November 2002 and was later extended to September 2008. Furthermore, a quality analysis of the methodological soundness of the studies in the review was performed. Paper II-IV. The aims were to compare EPT and VPT 8- to 10-year-old children with matched full-term controls considering: Prevalence of malocclusion traits and orthodontic treatment need (Paper II). Craniofacial morphology (Paper III). Mandibular function, signs and symptoms of TMD and headache (Paper IV). KEY FINDINGS IN PAPER I AND THE SUPPLEMENTARY SEARCH: Moderate scientific evidence existed for more malocclusion traits among premature children. Limited evidence was found for no delay in dental eruption, if corrected age was considered for the premature children. Insufficientwas considered for the premature children. Insufficient evidence was found for altered tooth-crown dimensions and permanent alteration of palatal morphology among prematurely children. Thus, further well-designed controlled studies which should also consider orthodontic treatment need, craniofacial morphology, TMD and headache are needed. KEY FINDINGS IN PAPER II

  6. El polimetilmetacrilato en la reconstrucción craneofacial The polymethylmethacrylate in the craniofacial repair

    Directory of Open Access Journals (Sweden)

    Pedro Ángel Peñón Vivas

    2011-06-01

    Full Text Available La reconstrucción de defectos craneofaciales constituye un reto para el cirujano maxilofacial. Si bien existe una amplia gama de materiales para la reconstrucción, cada cual tiene ventajas y desventajas además de indicaciones para su utilización. Por lo que nos hemos dado a la tarea de emplear el polimetilmetacrilato como una opción económica y efectiva en la reconstrucción de defectos craneofaciales. Con este objetivo se realizó un estudio descriptivo, retrospectivo, no comparativo, en el Servicio de Cirugía Maxilofacial del Hospital Universitario "Miguel Enríquez" en el periodo comprendido desde enero de 2006 a diciembre de 2008. Se incluyeron un total de 14 pacientes, los cuales recibieron tratamiento quirúrgico para la reconstrucción craneofacial mediante el empleo del polimetilmetacrilato. El mayor número de pacientes que recibieron tratamiento quirúrgico para la reconstrucción craneofacial con polimetilmetacrilato se encontró en el grupo de 16 a 25 años de edad, con un predominio del sexo masculino y mayor afectación de los pacientes de color de piel blanca. En todos los casos estudiados la etiología de la deformidad fue traumática; dentro de ellos el mayor por ciento le correspondió a los accidentes viales, seguido de los causados por violencia. El diagnóstico que predominó fue el de las fracturas orbitomalares de grado IV. El piso de órbita fue la localización o estructura más reconstruida. Se presentaron únicamente como complicaciones, la infección y la colección subcutánea. El polimetilmetacrilato es un material económico y efectivo que permite obtener excelentes resultados estéticos y funcionales en la reconstrucción de defectos craneofaciales adquiridos.The repair of craniofacial defects is a challenge for the maxillofacial surgeon. There are a great range of materials for reconstruction, where each has advantages and disadvantages as well as indications for its use. Polymethylmethacrylate is an

  7. Culture conditions for bovine embryonic stem cell-like cells isolated from blastocysts after external fertilization

    OpenAIRE

    Jin, Muzi; Wu, Asga; Dorzhin, Sergei; Yue, Qunhua; Ma, Yuzhen; Liu, Dongjun

    2012-01-01

    Although isolation and characterization of embryonic stem cells have been successful in cattle, maintenance of bovine embryonic stem cells in culture remains difficult. In this study, we compared different methods of cell passaging, feeder cell layers and medium conditions for bovine embryonic stem cell-like cells. We found that a murine embryonic fibroblast feeder layer is more suitable for embryonic stem cell-like cells than bovine embryonic fibroblasts. When murine embryonic fibroblasts we...

  8. Mesenchymal Stem Cells in Cardiology

    Science.gov (United States)

    White, Ian A.; Sanina, Cristina; Balkan, Wayne; Hare, Joshua M.

    2017-01-01

    Cardiovascular disease (CVD) accounts for more deaths globally than any other single disease. There are on average 1.5 million episodes of myocardial infarction (heart attack) each year in the United States alone with roughly one third resulting in death. There is therefore a major need for developing new and effective strategies to promote cardiac repair. Intramyocardial transplantation of mesenchymal stem cells (MSCs) has emerged as a leading contender in the pursuit of clinical intervention and therapy. MSCs are potent mediators of cardiac repair and are therefore an attractive tool in the development of pre-clinical and clinical trials. MSCs are capable of secreting a large array of soluble factors, which have had demonstrated effects on pathogenic cardiac remolding, fibrosis, immune activation and cardiac stem cell proliferation within the damaged heart. MSCs are also capable of differentiation into cardiomyocytes, endothelial cells and vascular smooth muscle cells, although the relative contribution of trilineage differentiation and paracrine effectors on cardiac repair remains the subject of active investigation. PMID:27236666

  9. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  10. Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish

    OpenAIRE

    Xiang, Fan; Hagos, Engda G.; Xu, Bo; Sias, Christina; Kawakami, Koichi; Burdine, Rebecca D.; Dougan, Scott T.

    2007-01-01

    In many vertebrates, extra-embryonic tissues are important signaling centers that induce and pattern the germ layers. In teleosts, the mechanism by which the extra-embryonic yolk syncytial layer (YSL) patterns the embryo is not understood. Although the Nodal-related protein Squint is expressed in the YSL, its role in this tissue is not known. We generated a series of stable transgenic lines with GFP under the control of squint genomic sequences. In all species, nodal-related genes induce thei...

  11. Single-cell RNA-seq analysis unveils a prevalent epithelial/mesenchymal hybrid state during mouse organogenesis.

    Science.gov (United States)

    Dong, Ji; Hu, Yuqiong; Fan, Xiaoying; Wu, Xinglong; Mao, Yunuo; Hu, Boqiang; Guo, Hongshan; Wen, Lu; Tang, Fuchou

    2018-03-14

    Organogenesis is crucial for proper organ formation during mammalian embryonic development. However, the similarities and shared features between different organs and the cellular heterogeneity during this process at single-cell resolution remain elusive. We perform single-cell RNA sequencing analysis of 1916 individual cells from eight organs and tissues of E9.5 to E11.5 mouse embryos, namely, the forebrain, hindbrain, skin, heart, somite, lung, liver, and intestine. Based on the regulatory activities rather than the expression patterns, all cells analyzed can be well classified into four major groups with epithelial, mesodermal, hematopoietic, and neuronal identities. For different organs within the same group, the similarities and differences of their features and developmental paths are revealed and reconstructed. We identify mutual interactions between epithelial and mesenchymal cells and detect epithelial cells with prevalent mesenchymal features during organogenesis, which are similar to the features of intermediate epithelial/mesenchymal cells during tumorigenesis. The comprehensive transcriptome at single-cell resolution profiled in our study paves the way for future mechanistic studies of the gene-regulatory networks governing mammalian organogenesis.

  12. Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease.

    Science.gov (United States)

    Venkatesh, Katari; Sen, Dwaipayan

    2017-01-01

    Cell repair/replacing strategies for neurodegenerative diseases such as Parkinson's disease depend on well-characterized dopaminergic neuronal candidates that are healthy and show promising effect on the rejuvenation of degenerated area of the brain. Therefore, it is imperative to develop innovative therapeutic strategies that replace damaged neurons with new/functional dopaminergic neurons. Although several research groups have reported the generation of neural precursors/neurons from human/ mouse embryonic stem cells and mesenchymal stem cells, the latter is considered to be an attractive therapeutic candidate because of its high capacity for self-renewable, no adverse effect to allogeneic versus autologous transplants, high ethical acceptance and no teratoma formation. Therefore, mesenchymal stem cells can be considered as an ideal source for replacing lost cells in degenerative diseases like Parkinson's. Hence, the use of these cells in the differentiation of dopaminergic neurons becomes significant and thrives as a therapeutic approach to treat Parkinson's disease. Here we highlight the basic biology of mesenchymal stem cells, their differentiation potential into dopaminergic neurons and potential use in the clinics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    International Nuclear Information System (INIS)

    Pang, Lisa Y.; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J.

    2011-01-01

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology

  14. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Lisa Y., E-mail: lisa.pang@ed.ac.uk; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J. [Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG (United Kingdom)

    2011-03-30

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

  15. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

    Directory of Open Access Journals (Sweden)

    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  16. Analysed cap mesenchyme track data from live imaging of mouse kidney development

    Directory of Open Access Journals (Sweden)

    James G. Lefevre

    2016-12-01

    Full Text Available This article provides detailed information on manually tracked cap mesenchyme cells from timelapse imaging of multiple ex vivo embryonic mouse kidneys. Cells were imaged for up to 18 h at 15 or 20 min intervals, and multiple cell divisions were tracked. Positional data is supplemented with a range of information including the relative location of the closest ureteric tip and a correction for drift due to bulk movement and tip growth. A subset of tracks were annotated to indicate the presence of processes attached to the ureteric epithelium. The calculations used for drift correction are described, as are the main methods used in the analysis of this data for the purpose of describing cap cell motility. The outcomes of this analysis are discussed in “Cap mesenchyme cell swarming during kidney development is influenced by attraction, repulsion, and adhesion to the ureteric tip” (A.N. Combes, J.G. Lefevre, S. Wilson, N.A. Hamilton, M.H. Little, 2016 [1].

  17. Titania-polymeric powder coatings with nano-topography support enhanced human mesenchymal cell responses.

    Science.gov (United States)

    Mozumder, Mohammad Sayem; Zhu, Jesse; Perinpanayagam, Hiran

    2012-10-01

    Titanium implant osseointegration is dependent on the cellular response to surface modifications and coatings. Titania-enriched nanocomposite polymeric resin coatings were prepared through the application of advanced ultrafine powder coating technology. Their surfaces were readily modified to create nano-rough (topographies that supported human embryonic palatal mesenchymal cell responses. Energy dispersive x-ray spectroscopy confirmed continuous and homogenous coatings with a similar composition and even distribution of titanium. Scanning electron microscopy (SEM) showed complex micro-topographies, and atomic force microscopy revealed intricate nanofeatures and surface roughness. Cell counts, mitochondrial enzyme activity reduction of yellow 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to dark purple, SEM, and inverted fluorescence microscopy showed a marked increase in cell attachment, spreading, proliferation, and metabolic activity on the nanostructured surfaces. Reverse Transcription- Polymerase Chain Reaction (RT-PCR) analysis showed that type I collagen and Runx2 expression were induced, and Alizarin red staining showed that mineral deposits were abundant in the cell cultures grown on nanosurfaces. This enhancement in human mesenchymal cell attachment, growth, and osteogenesis were attributed to the nanosized surface topographies, roughness, and moderate wetting characteristics of the coatings. Their dimensional similarity to naturally occurring matrix proteins and crystals, coupled with their increased surface area for protein adsorption, may have facilitated the response. Therefore, this application of ultrafine powder coating technology affords highly biocompatible surfaces that can be readily modified to accentuate the cellular response. Copyright © 2012 Wiley Periodicals, Inc.

  18. Craniofacial morphology of Dutch patients with bilateral cleft lip and palate and noncleft controls at the age of 15 years

    NARCIS (Netherlands)

    van den Dungen, G.M.; Ongkosuwito, E.M.; Aartman, I.H.A.; Prahl-Andersen, B.

    2008-01-01

    Objective: Comparison of craniofacial morphology in bilateral cleft lip and palate patients to that of a noncleft control group at the age of 15 years. Design: A cross-sectional study of cephalometric data. Subjects and Methods: Cephalometric records of 41 consecutive patients (32 boys and 9 girls)

  19. Postnatal treatment factors affecting craniofacial morphology of unilateral cleft lip and palate (UCLP) patients in a Japanese population.

    Science.gov (United States)

    Alam, M K; Iida, J; Sato, Y; Kajii, Takashi S

    2013-12-01

    We have evaluated the craniofacial morphology of Japanese patients with unilateral cleft lip and palate (UCLP) and assessed the various postnatal factors that affect it. Lateral cephalograms of 140 subjects (mean (SD) aged 7 (2) years) with UCLP were taken before orthodontic treatment. Surgeons from Hokkaido University Hospital had done the primary operations. The craniofacial morphology was assessed by angular and linear cephalometric measurements. Cheiloplasty, palatoplasty, and preoperative orthopaedic treatment were chosen as postnatal factors. To compare the assessments of the postnatal factors, we made angular and linear cephalometric measurements for each subject and converted them into Z scores in relation to the mean (SD) of the two variables. Subjects treated by the modified Millard cheiloplasty had larger sella-nasion-point A (SNA) and nasion-point A-pogonion (NA-POG) measurements than subjects treated by the modified Millard with a vomer flap cheiloplasty. Two-stage palatoplasty showed consistently better craniofacial morphology than the other palatoplasty. Subjects who had preoperative orthopaedic treatment with a Hotz plate had significantly larger upper incisor/sella-nasion (U1-SN) measurements than who had no preoperative orthopaedic treatment or an active plate. We conclude that in subjects treated by a modified Millard type of cheiloplasty, a two-stage palatoplasty, and a Hotz plate there were fewer adverse effects on craniofacial morphology. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  20. Craniofacial morphology in complete unilateral cleft lip and palate patients consecutively treated with 1-stage repair of the cleft.

    NARCIS (Netherlands)

    Fudalej, P.S.; Surowiec, Z.; Offert, B.; Dudkiewicz, Z.; Katsaros, C.

    2010-01-01

    OBJECTIVE: To retrospectively evaluate the craniofacial morphology of children with a complete unilateral cleft lip and palate treated with a 1-stage simultaneous cleft repair performed in the first year of life. METHODS: Cephalograms and extraoral profile photographs of 61 consecutively treated

  1. Craniofacial morphology, head posture, and nasal respiratory resistance in obstructive sleep apnoea : An inter-ethnic comparison

    NARCIS (Netherlands)

    Wong, M.L.; Sandham, John; Ang, PK; Wong, DC; Tan, WC; Huggare, J

    The aim of this study was to measure craniofacial morphology and nasal respiratory resistance (NRR) in Malay, Indian and Chinese subjects with obstructive sleep apnoea (OSA). The sample consisted of 34 male subjects, 27-52 years of age (Malay n = 11, which included five mild and six moderate-severe

  2. Does postoperative 'M' technique (R) massage with or without mandarin oil reduce infants' distress after major craniofacial surgery?

    NARCIS (Netherlands)

    de Jong, Marjan; Lucas, Cees; Bredero, Hansje; van Adrichem, Leon; Tibboel, Dick; van Dijk, Monique

    2012-01-01

    de jong m., lucas c., bredero h., van adrichem l., tibboel d. & van dijk m. (2011) Does postoperative M technique (R) massage with or without mandarin oil reduce infants distress after major craniofacial surgery? Journal of Advanced Nursing68(6), 17481757. Abstract Aim. This article is a report of a

  3. Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects

    Directory of Open Access Journals (Sweden)

    Swapnalee Sarmah

    2013-08-01

    Fetal alcohol spectrum disorder (FASD occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell, prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented that characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression was not affected by ethanol exposure, but E-cadherin distribution, which controls epiboly and gastrulation, was changed. E-cadherin was redistributed into cytoplasmic aggregates in blastomeres and dramatically redistributed in the extraembryonic yolk cell. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a, which controls epiboly, was significantly reduced in ethanol exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.

  4. Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test

    International Nuclear Information System (INIS)

    Nieden, Nicole I. zur; Davis, Lesley A.; Rancourt, Derrick E.

    2010-01-01

    Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantification of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID 50 s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca 2+ deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming.

  5. Mesomere-derived glutamate decarboxylase-expressing blastocoelar mesenchyme cells of sea urchin larvae

    Directory of Open Access Journals (Sweden)

    Hideki Katow

    2013-12-01

    The ontogenetic origin of blastocoelar glutamate decarboxylase (GAD-expressing cells (GADCs in larvae of the sea urchin Hemicentrotus pulcherrimus was elucidated. Whole-mount in situ hybridisation (WISH detected transcription of the gene that encodes GAD in H. pulcherrimus (Hp-gad in unfertilised eggs and all blastomeres in morulae. However, at and after the swimming blastula stage, the transcript accumulation was particularly prominent in clumps of ectodermal cells throughout the embryonic surface. During the gastrula stage, the transcripts also accumulated in the endomesoderm and certain blastocoelar cells. Consistent with the increasing number of Hp-gad transcribing cells, immunoblot analysis indicated that the relative abundance of Hp-Gad increased considerably from the early gastrula stage until the prism stage. The expression pattern of GADCs determined by immunohistochemistry was identical to the pattern of Hp-gad transcript accumulation determined using WISH. In early gastrulae, GADCs formed blastocoelar cell aggregates around the blastopore with primary mesenchyme cells. The increase in the number of blastocoelar GADCs was inversely proportional to the number of ectodermal GADCs ranging from a few percent of total GADCs in early gastrulae to 80% in late prism larvae; this depended on ingression of ectodermal GADCs into the blastocoel. Some of the blastocoelar GADCs were fluorescein-positive in the larvae that developed from the 16-cell stage chimeric embryos; these comprised fluorescein-labeled mesomeres and unlabelled macromeres and micromeres. Our finding indicates that some of the blastocoelar GADCs are derived from the mesomeres and thus they are the new group of mesenchyme cells, the tertiary mesenchyme cells.

  6. Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition.

    Science.gov (United States)

    Saunders, Lindsay R; McClay, David R

    2014-04-01

    Epithelial-mesenchymal transition (EMT) is a fundamental cell state change that transforms epithelial to mesenchymal cells during embryonic development, adult tissue repair and cancer metastasis. EMT includes a complex series of intermediate cell state changes including remodeling of the basement membrane, apical constriction, epithelial de-adhesion, directed motility, loss of apical-basal polarity, and acquisition of mesenchymal adhesion and polarity. Transcriptional regulatory state changes must ultimately coordinate the timing and execution of these cell biological processes. A well-characterized gene regulatory network (GRN) in the sea urchin embryo was used to identify the transcription factors that control five distinct cell changes during EMT. Single transcription factors were perturbed and the consequences followed with in vivo time-lapse imaging or immunostaining assays. The data show that five different sub-circuits of the GRN control five distinct cell biological activities, each part of the complex EMT process. Thirteen transcription factors (TFs) expressed specifically in pre-EMT cells were required for EMT. Three TFs highest in the GRN specified and activated EMT (alx1, ets1, tbr) and the 10 TFs downstream of those (tel, erg, hex, tgif, snail, twist, foxn2/3, dri, foxb, foxo) were also required for EMT. No single TF functioned in all five sub-circuits, indicating that there is no EMT master regulator. Instead, the resulting sub-circuit topologies suggest EMT requires multiple simultaneous regulatory mechanisms: forward cascades, parallel inputs and positive-feedback lock downs. The interconnected and overlapping nature of the sub-circuits provides one explanation for the seamless orchestration by the embryo of cell state changes leading to successful EMT.

  7. Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds.

    Science.gov (United States)

    Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M

    2012-08-15

    The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Isolation of a primate embryonic stem cell line.

    OpenAIRE

    Thomson, J A; Kalishman, J; Golos, T G; Durning, M; Harris, C P; Becker, R A; Hearn, J P

    1995-01-01

    Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. Here we report the derivation of a cloned cell line (R278.5) from a rhesus monkey blastocyst that remains undifferentiated in continuous passage for > 1 year, maintains a normal XY karyotype, and expresses the cell surface markers (alkaline phosphatase, stage-specific embryonic antigen 3, st...

  9. Radiographic cephalometry analysis of head posture and craniofacial morphology in oral breathing children

    Directory of Open Access Journals (Sweden)

    Vukićević Vladanka

    2017-01-01

    Full Text Available Background/Aim. Nasal breathing plays an important role in overall physical growth and mental development, as well as in the growth of the craniofacial complex. Oral breathing over a long period of time, can cause changes in position of the head relative to the cervical spine and jaw relationship. It can cause an open bite and the narrowness of the maxillary arch due to increased pressure of strained face. The aim of this study was to analyze the position of the head and craniofacial morphology in oral breathing children, and compare the values obtained compared with those of the same parameters in nasal brething children. Methods. We analyzed the profile cephalometric radiographs of 60 patients who had various orthodontic problems. In the first group there were 30 patients aged 8–14 years, in which oral breathing is confirmed by clinical examination. In the second group there were 30 patients of the same age who had orthodontic problems, but did not show clinical signs of oral breathing. The analyses covered the following: craniocervical angle (NS/OPT, the length of the anterior cranial base (NS, anterior facial height (N-Me, posterior facial height (S-Go, the angle of maxillary prognathism (SNA, angle of mandibular prognathism (SNB, difference between angles SNA and SNB (ANB angle, the angle of the basal planes of the jaws (SpP/MP, cranial base angle (NSB, and the angle of facial convexity (NA/Apg. Results. The average value of the craniocervical angle (NS/OPT was significantly higher in OB children (p = 0.004. There were significantly different values of SNA (p < 0.001, ANB (p < 0.001, NA/APg (p < 0.001 and length of the anterior cranial base (NS (p = 0.024 between groups. Conclusion. Oral breathing children have pronounced retroflexion of the head in relation to the cervical spine compared to nasal breathing children, and the most prominent characteristics of the craniofacial morphology of skeletal jaw relationship of class II and

  10. Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

    Directory of Open Access Journals (Sweden)

    Schwend Tyler

    2009-11-01

    Full Text Available Abstract Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC. Genetic studies in zebrafish and mice have established that the Hedgehog (Hh-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE, which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia 12. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1 for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1. Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to

  11. Effectiveness of the cervical vertebral maturation method to predict postpeak circumpubertal growth of craniofacial structures.

    Science.gov (United States)

    Fudalej, Piotr; Bollen, Anne-Marie

    2010-01-01

    Our aim was to assess effectiveness of the cervical vertebral maturation (CVM) method to predict circumpubertal craniofacial growth in the postpeak period. The CVM stage was determined in 176 subjects (51 adolescent boys and 125 adolescent girls) on cephalograms taken at the end of treatment (T2; mean ages, 15.75 years [boys] and 15.23 years [girls]) in subjects from the postretention database at the University of Washington in Seattle. Craniofacial growth was evaluated from the following measurements on cephalograms at T2 and end of follow-up (T3) (mean ages, 29.01 years [men] and 28.08 years [women]): condylion to gnathion, condylion to gonion, gonion to gnathion, sella to gnathion, nasion to menton, anterior nasal spine to menton, and sella to gonion. The change of each variable from T2 to T3 was assessed with paired t tests. Parametric (t tests or analysis of variance [ANOVA]) or nonparametric (Mann-Whitney or Kruskal-Wallis) tests were used to detect intergroup differences. One hundred eight subjects (35 boys, 73 girls) demonstrated CVM stage 3, 56 (16 boys, 40 girls) were in CVM stage 4, and 12 (all girls) were in CVM stage 5 at T2. Intrasex comparisons showed that boys in CVM stages 3 and 4 could be differentiated regarding changes of all variables. In the girls, only those in CVM stages 3 and 4 could be differentiated based on the amount of changes of 2 measurements: condylion to gonion and sella to gonion. Intersex comparisons showed that boys in CVM stage 3 had significantly more changes than girls (P <0.01). Boys in CVM stage 4 showed significant differences compared with girls in CVM stage 4 for only 2 variables (sella to gonion and condylion to gonion; P <0.001 and P = 0.012, respectively). The CVM method was modestly effective in determining the amount of postpeak circumpubertal craniofacial growth. Copyright 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  12. An Anthropometric Study of Cranio-Facial Measurements and Their Correlation with Vertical Dimension of Occlusion among Saudi Arabian Subpopulations.

    Science.gov (United States)

    Majeed, Muhammed Irfan; Haralur, Satheesh B; Khan, Muhammed Farhan; Al Ahmari, Maram Awdah; Al Shahrani, Nourah Falah; Shaik, Sharaz

    2018-04-15

    Determining and restoring physiological vertical dimension of occlusion (VDO) is the critical step during complete mouth rehabilitation. The improper VDO compromises the aesthetics, phonetics and functional efficiency of the prosthesis. Various methods are suggested to determine the accurate VDO, including the facial measurements in the clinical situations with no pre-extraction records. The generalisation of correlation between the facial measurements to VDO is criticised due to gender dimorphism and racial differences. Hence, it is prudent to verify the hypothesis of facial proportion and correlation of lower third of the face to remaining craniofacial measurements in different ethnic groups. The objective of the study was to evaluate the correlation of craniofacial measurements and OVD in the Saudi-Arabian ethnic group. Total of 228 participants from Saudi-Arabian Ethnic group were randomly recruited in this cross-sectional study. Fifteen craniofacial measurements were recorded with modified digital Vernier callipers, and OVD was recorded at centric occlusion. The obtained data were analysed by using the Spearman's correlation and linear regression analysis. The Mean OVD in male participants was higher (69.25 ± 5.54) in comparison to female participants (57.41 ± 5.32). The craniofacial measurement of Exocanthion-right labial commissure and the Mesial wall of the right external auditory canal-orbitale lateral had a strong positive correlation with VDO. The strong correlation was recorded with a trichion-upper border of right eyebrow line and trichion-Nasion only in males. Meanwhile, the length of an auricle recorded the positive correlation in female participants. Being simple and non-invasive technique, craniofacial measurements and linear equations could be routinely utilised to determine VDO.

  13. Facial Phenotyping by Quantitative Photography Reflects Craniofacial Morphology Measured on Magnetic Resonance Imaging in Icelandic Sleep Apnea Patients

    Science.gov (United States)

    Sutherland, Kate; Schwab, Richard J.; Maislin, Greg; Lee, Richard W.W.; Benedikstdsottir, Bryndis; Pack, Allan I.; Gislason, Thorarinn; Juliusson, Sigurdur; Cistulli, Peter A.

    2014-01-01

    Study Objectives: (1) To determine whether facial phenotype, measured by quantitative photography, relates to underlying craniofacial obstructive sleep apnea (OSA) risk factors, measured with magnetic resonance imaging (MRI); (2) To assess whether these associations are independent of body size and obesity. Design: Cross-sectional cohort. Setting: Landspitali, The National University Hospital, Iceland. Participants: One hundred forty patients (87.1% male) from the Icelandic Sleep Apnea Cohort who had both calibrated frontal and profile craniofacial photographs and upper airway MRI. Mean ± standard deviation age 56.1 ± 10.4 y, body mass index 33.5 ± 5.05 kg/m2, with on-average severe OSA (apnea-hypopnea index 45.4 ± 19.7 h-1). Interventions: N/A. Measurements and Results: Relationships between surface facial dimensions (photos) and facial bony dimensions and upper airway soft-tissue volumes (MRI) was assessed using canonical correlation analysis. Photo and MRI craniofacial datasets related in four significant canonical correlations, primarily driven by measurements of (1) maxillary-mandibular relationship (r = 0.8, P photography and MRI. This study confirms that facial photographic phenotype reflects underlying aspects of craniofacial skeletal abnormalities associated with OSA. Therefore, facial photographic phenotyping may be a useful tool to assess intermediate phenotypes for OSA, particularly in large-scale studies. Citation: Sutherland K, Schwab RJ, Maislin G, Lee RW, Benedikstdsottir B, Pack AI, Gislason T, Juliusson S, Cistulli PA. Facial phenotyping by quantitative photography reflects craniofacial morphology measured on magnetic resonance imaging in icelandic sleep apnea patients. SLEEP 2014;37(5):959-968. PMID:24790275

  14. The Cross-talk Between TGF-β1 and Dlk1 Mediates Early Chondrogenesis During Embryonic Endochondral Ossification

    DEFF Research Database (Denmark)

    Taipaleenmaki, Hanna; M, Linda; Chen, Li

    2012-01-01

    Dlkl/Pref-1/FA1 (delta like-1/preadipocyte factor-1/Fetal Antigen-1) is a novel surface marker for embryonic chondroprogenitor cells undergoing lineage progression from proliferation to prehypertrophic stages. However, mechanisms mediating control of its expression during chondrogenesis...... during mesenchymal condensation and chondrocyte proliferation, in parallel with expression of Sox9 and Col2a1, and was down-regulated upon the expression of Col10a1 by hypertrophic chondrocytes. Among a number of molecules that affected chondrogenesis, TGF-β1-induced proliferation of chondroprogenitors...... was associated with decreased Dlk1 expression. This effect was abolished by TGF-β signalling inhibitor SB431542, suggesting regulation of Dlk1/FA1 by TGF-β1 signalling in chondrogenesis. TGF-β1-induced Smad phosphorylation and chondrogenesis were significantly increased in Dlk1 (-/-) MEF, while they were blocked...

  15. The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

    Science.gov (United States)

    Barriga, Elias H.; Maxwell, Patrick H.

    2013-01-01

    One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells. PMID:23712262

  16. Cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube

    NARCIS (Netherlands)

    Fijnvandraat, Arnoud C.; van Ginneken, Antoni C. G.; de Boer, Piet A. J.; Ruijter, Jan M.; Christoffels, Vincent M.; Moorman, Antoon F. M.; Lekanne Deprez, Ronald H.

    2003-01-01

    OBJECTIVE: After formation of the linear heart tube a chamber-specific program of gene expression becomes active that underlies the formation of the chamber myocardium. To assess whether this program is recapitulated in in vitro differentiated embryonic stem cells, we performed qualitative and

  17. In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell-Derived Osteoprogenitors

    Directory of Open Access Journals (Sweden)

    Intekhab Islam

    2016-01-01

    Full Text Available Cellular therapy using stem cells in bone regeneration has gained increasing interest. Various studies suggest the clinical utility of osteoprogenitors-like mesenchymal stem cells in bone regeneration. However, limited availability of mesenchymal stem cells and conflicting evidence on their therapeutic efficacy limit their clinical application. Human embryonic stem cells (hESCs are potentially an unlimited source of healthy and functional osteoprogenitors (OPs that could be utilized for bone regenerative applications. However, limited ability to track hESC-derived progenies in vivo greatly hinders translational studies. Hence, in this study, we aimed to establish hESC-derived OPs (hESC-OPs expressing green fluorescent protein (GFP and to investigate their osteogenic differentiation potential in vitro. We fluorescently labelled H9-hESCs using a plasmid vector encoding GFP. The GFP-expressing hESCs were differentiated into hESC-OPs. The hESC-OPsGFP+ stably expressed high levels of GFP, CD73, CD90, and CD105. They possessed osteogenic differentiation potential in vitro as demonstrated by increased expression of COL1A1, RUNX2, OSTERIX, and OPG transcripts and mineralized nodules positive for Alizarin Red and immunocytochemical expression of osteocalcin, alkaline phosphatase, and collagen-I. In conclusion, we have demonstrated that fluorescently labelled hESC-OPs can maintain their GFP expression for the long term and their potential for osteogenic differentiation in vitro. In future, these fluorescently labelled hESC-OPs could be used for noninvasive assessment of bone regeneration, safety, and therapeutic efficacy.

  18. Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead.

    Science.gov (United States)

    Bhartiya, Deepa; Shaikh, Ambreen; Anand, Sandhya; Patel, Hiren; Kapoor, Sona; Sriraman, Kalpana; Parte, Seema; Unni, Sreepoorna

    2016-12-01

    Both pluripotent very small embryonic-like stem cells (VSELs) and induced pluripotent stem (iPS) cells were reported in 2006. In 2012, a Nobel Prize was awarded for iPS technology whereas even today the very existence of VSELs is not well accepted. The underlying reason is that VSELs exist in low numbers, remain dormant under homeostatic conditions, are very small in size and do not pellet down at 250-280g. The VSELs maintain life-long tissue homeostasis, serve as a backup pool for adult stem cells and are mobilized under stress conditions. An imbalance in VSELs function (uncontrolled proliferation) may result in cancer. The electronic database 'Medline/Pubmed' was systematically searched with the subject heading term 'very small embryonic-like stem cells'. The most primitive stem cells that undergo asymmetric cell divisions to self-renew and give rise to progenitors still remain elusive in the hematopoietic system and testes, while the presence of stem cells in ovary is still being debated. We propose to review the available literature on VSELs, the methods of their isolation and characterization, their ontogeny, how they compare with embryonic stem (ES) cells, primordial germ cells (PGCs) and iPS cells, and their role in maintaining tissue homeostasis. The review includes a look ahead on how VSELs will result in paradigm shifts in basic reproductive biology. Adult tissue-specific stem cells including hematopoietic, spermatogonial, ovarian and mesenchymal stem cells have good proliferation potential and are indeed committed progenitors (with cytoplasmic OCT-4), which arise by asymmetric cell divisions of pluripotent VSELs (with nuclear OCT-4). VSELs are the most primitive stem cells and postulated to be an overlapping population with the PGCs. Rather than migrating only to the gonads, PGCs migrate and survive in various adult body organs throughout life as VSELs. VSELs express both pluripotent and PGC-specific markers and are epigenetically and developmentally

  19. Dedicated Stereophotogrammetric X-Ray System For Craniofacial Research And Treatment Planning

    Science.gov (United States)

    Baumrind, Sheldon; Moffitt, Francis; Curry, Sean; Isaacson, Robert J.

    1983-07-01

    We have constructed and brought into use what we believe to be the first dedicated coplanar craniofacial stereometric x-ray system for clinical use. Paired Machlett Dynamax 50/58 x-ray tubes with 0.3 mm focal spots are employed. Displacement between emitters is 16 inches. The focus film distance for both emitters is 66.5 inches. The mid-sagittal plane to focus distance is 60 inches. One film of each stereo pair conforms with the standards of the Second Roentgenocephalometric Workshop and can be used to make all standard two-dimensional orthodontic and cephalometric measurements. When supplemented by data from the conjugate film, a three-dimensional coordinate map can be generated as a machine operation. Specialized complementary software has been developed to increase the reliability of landmark location both in two and in three dimensions.

  20. Head posture and cervicovertebral and craniofacial morphology in patients with craniomandibular dysfunction.

    Science.gov (United States)

    Huggare, J A; Raustia, A M

    1992-07-01

    A relationship between particular characteristics of dental occlusion and craniomandibular disorders (CMD) has been reported, while less attention has been focused on the possible effect of dysfunction of the masticatory system on head posture or cervicovertebral and craniofacial morphology. Natural head position roentgen-cephalograms of 16 young adults with complete dentition taken before and after stomatognathic treatment displayed an extended head posture, smaller size of the uppermost cervical vertebrae, decreased posterior to anterior face height ratio, and a flattened cranial base as compared with age- and sex-matched healthy controls. The lordosis of the cervical spine straightened after stomatognathic treatment. The results are an indication of the close interrelationship between the masticatory muscle system and the muscles supporting the head, and lead to speculation on the principles of treating craniomandibular disorders.

  1. International confederation for cleft lip and palate and related craniofacial anomalies task force report: holistic outcomes.

    Science.gov (United States)

    Broder, Hillary L

    2014-11-01

    Objective : This paper describes the process and outcomes of the 2013 American Cleft Palate-Craniofacial Association task force on Holistic Outcomes. The goals and membership of the task force are presented. Methods : Using internet communication, the group introduced themselves, shared ideas and information related to holistic assessment and implementation of using a validated holistic measure, the Child Oral Health Impact Profile (COHIP) at participating international sites. Results : Data from the sites were analyzed using descriptive statistics. Administration of the COHIP was successful. It varied from self-completion as well as verbal presentation due to language differences and a function of the short time period to complete collection. Additionally qualitative comments were reported by the task force site directors. Conclusions : Future directions for holistic assessment and communication among task force members and sites were discussed at the Congress and are presented in this report.

  2. Effect of Injection Molding Melt Temperatures on PLGA Craniofacial Plate Properties during In Vitro Degradation

    Directory of Open Access Journals (Sweden)

    Liliane Pimenta de Melo

    2017-01-01

    Full Text Available The purpose of this article is to present mechanical and physicochemical properties during in vitro degradation of PLGA material as craniofacial plates based on different values of injection molded temperatures. Injection molded plates were submitted to in vitro degradation in a thermostat bath at 37 ± 1°C by 16 weeks. The material was removed after 15, 30, 60, and 120 days; then bending stiffness, crystallinity, molecular weights, and viscoelasticity were studied. A significant decrease of molecular weight and mechanical properties over time and a difference in FT-IR after 60 days showed faster degradation of the material in the geometry studied. DSC analysis confirmed that the crystallization occurred, especially in higher melt temperature condition. DMA analysis suggests a greater contribution of the viscous component of higher temperature than lower temperature in thermomechanical behavior. The results suggest that physical-mechanical properties of PLGA plates among degradation differ per injection molding temperatures.

  3. Bioinformatic analysis of Msx1 and Msx2 involved in craniofacial development.

    Science.gov (United States)

    Dai, Jiewen; Mou, Zhifang; Shen, Shunyao; Dong, Yuefu; Yang, Tong; Shen, Steve Guofang

    2014-01-01

    Msx1 and Msx2 were revealed to be candidate genes for some craniofacial deformities, such as cleft lip with/without cleft palate (CL/P) and craniosynostosis. Many other genes were demonstrated to have a cross-talk with MSX genes in causing these defects. However, there is no systematic evaluation for these MSX gene-related factors. In this study, we performed systematic bioinformatic analysis for MSX genes by combining using GeneDecks, DAVID, and STRING database, and the results showed that there were numerous genes related to MSX genes, such as Irf6, TP63, Dlx2, Dlx5, Pax3, Pax9, Bmp4, Tgf-beta2, and Tgf-beta3 that have been demonstrated to be involved in CL/P, and Fgfr2, Fgfr1, Fgfr3, and Twist1 that were involved in craniosynostosis. Many of these genes could be enriched into different gene groups involved in different signaling ways, different craniofacial deformities, and different biological process. These findings could make us analyze the function of MSX gens in a gene network. In addition, our findings showed that Sumo, a novel gene whose polymorphisms were demonstrated to be associated with nonsyndromic CL/P by genome-wide association study, has protein-protein interaction with MSX1, which may offer us an alternative method to perform bioinformatic analysis for genes found by genome-wide association study and can make us predict the disrupted protein function due to the mutation in a gene DNA sequence. These findings may guide us to perform further functional studies in the future.

  4. SURGICAL TREATMENT OF UPPER AND MIDDLE FACIAL ZONE TRAUMAS IN PROGRESS OF CONCOMITANT TRAUMATIC CRANIOFACIAL INJURIES.

    Science.gov (United States)

    Lagvilava, G; Gvenetadze, Z; Toradze, G; Devidze, I; Gvenetadze, G

    2015-09-01

    In 2012-2015, 207 patients with concomitant craniofacial injuries, who underwent surgical treatment, were observed; among them 176 were men and 31- women. Age of the patients ranged from 16 to 60 years. According to localization and severity of trauma and a priority of surgical intervention, the patients conventionally were divided into 3 groups by the authors: I group (65 patients) - craniofacial injuries; the skull as well as upper and middle areas of face (subcranial and frontobasal fractures) were affected (fractured). II group (80 patients) - severe traumatic injuries of upper and especially middle zones of the face, accompanied with closed craniocerebral trauma, no need in neurosurgery. III group (62 patients) -on the background of serious head traumas, the injuries of face bones were less severe (injury of one or two anatomic areas with displacement of fractured fragments but without bone tissue defects) According to the obtained results a priority was always given to the neurosurgery (vital testimony).The reconstructive surgeries on face skeleton was conducted in combination involving neurosurgeons (I group patients). Reconstructive surgeries of facial bones were conducted in the patients of II group, immediately or at primary deferred period of time but in the patients of III group the surgical procedures for removal of early secondary or traumatic residual fractures have been performed. Reposition of the fractured facial bone fragments was performed in an open way and fixation was carried out by titanium plates and mesh cage (at bone tissue defect). For prevention and elimination of post-traumatic inflammatory processes, the final stage of surgical intervention was: sanation of nasal accessory sinuses and catheterization (5-7 days) of external carotid arteries for administration of antibiotics and other medical preparations. Early and differentiated approach to face injuries, worsening in the course of craniocephalic trauma was not revealed in any patient

  5. Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in hair sheep of northeastern Brazil.

    Science.gov (United States)

    Dantas, F P M; Medeiros, G X; Figueiredo, A P M; Thompson, K; Riet-Correa, F

    2014-01-01

    This paper reports a newly described form of skeletal dysplasia affecting Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a short head and in some cases the animals are smaller and more compact than sheep of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face characteristic of the breed. Dwarf lambs were much smaller than normal, with short legs, a domed head with retruded muzzle and protruded mandible, sternal deformities and exophthalmic eyes situated more laterally in the face than normal. Microscopical examination of long bones of the limbs, bones of the base of the skull and vertebrae showed no lesions. Bones from four affected lambs and one control lamb were macerated for morphometric examination. Although the length of the spinal cord was similar, there was disproportionate shortening of the appendicular bones, particularly the distal segments. Thus the disease was defined as a skeletal dysplasia characterized by craniofacial deformity and disproportionate dwarfism. It is suggested that the disease is inherited as an incomplete dominant trait. The shortened face, which is a feature of the Cabugi breed, may represent the heterozygous state and the more severe, often lethal, dwarfism may occur in homozygotes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Thin-plate spline analysis of allometry and sexual dimorphism in the human craniofacial complex.

    Science.gov (United States)

    Rosas, Antonio; Bastir, Markus

    2002-03-01

    The relationship between allometry and sexual dimorphism in the human craniofacial complex was analyzed using geometric morphometric methods. Thin-plate splines (TPS) analysis has been applied to investigate the lateral profile of complete adult skulls of known sex. Twenty-nine three-dimensional (3D) craniofacial and mandibular landmark coordinates were recorded from a sample of 52 adult females and 52 adult males of known age and sex. No difference in the influence of size on shape was detected between sexes. Both size and sex had significant influences on shape. As expected, the influence of centroid size on shape (allometry) revealed a shift in the proportions of the neurocranium and the viscerocranium, with a marked allometric variation of the lower face. Adjusted for centroid size, males presented a relatively larger size of the nasopharyngeal space than females. A mean-male TPS transformation revealed a larger piriform aperture, achieved by an increase of the angulation of the nasal bones and a downward rotation of the anterior nasal floor. Male pharynx expansion was also reflected by larger choanae and a more posteriorly inclined basilar part of the occipital clivus. Male muscle attachment sites appeared more pronounced. In contrast, the mean-female TPS transformation was characterized by a relatively small nasal aperture. The occipital clivus inclined anteriorly, and muscle insertion areas became smoothed. Besides these variations, both maxillary and mandibular alveolar regions became prognathic. The sex-specific TPS deformation patterns are hypothesized to be associated with sexual differences in body composition and energetic requirements. Copyright 2002 Wiley-Liss, Inc.

  7. In vitro quantification of strain patterns in the craniofacial skeleton due to masseter and temporalis activities.

    Science.gov (United States)

    Maloul, Asmaa; Regev, Eran; Whyne, Cari M; Beek, Marteen; Fialkov, Jeffrey A

    2012-09-01

    Many complications in craniofacial surgery can be attributed to a lack of characterization of facial skeletal strain patterns. This study aimed to delineate human midfacial strain patterns under uniform muscle loading. The left sides of 5 fresh-frozen human cadaveric heads were dissected of all soft tissues except the temporalis and masseter muscles. Tensile forces were applied to the free mandibular ends of the muscles. Maxillary alveolar arches were used to restrain the skulls. Eight strain gauges were bonded to the surface of the midface to measure the strain under single muscle loading conditions (100 N). Maxillary strain gauges revealed a biaxial load state for both muscles. Thin antral bone experienced high maximum principal tensile strains (maximum of 685.5 με) and high minimum principal compressive strains (maximum of -722.44 με). Similar biaxial patterns of lower magnitude were measured on the zygoma (maximum of 208.59 με for maximum principal strains and -78.11 με for minimum principal strains). Results, consistent for all specimens and counter to previously accepted concepts of biomechanical behavior of the midface under masticatory muscle loading, included high strain in the thin maxillary antral wall, rotational bending through the maxilla and zygoma, and a previously underestimated contribution of the temporalis muscle. This experimental model produced repeatable strain patterns quantifying the mechanics of the facial skeleton. These new counterintuitive findings underscore the need for accurate characterization of craniofacial strain patterns to address problems in the current treatment methods and develop robust design criteria.

  8. A lateral cephalometric study of craniofacial variation in Korean child twins

    International Nuclear Information System (INIS)

    Lee, Sang Rae; You, Dong Soo

    1974-01-01

    A study was performed to investigate the degree of similarities and differences in components of craniofacial complex between Korean twins and normal children by lateral cephalometric analysis. Dimensions of S-N, S-Ba, N-Ba, Go-Me, Ar-Go and Ar-Me were plotted against linear measurement and angles of N-S-Ba and gonial against angular measurement in twins and control groups. The lateral cephalograms of twin were composed of 88 twins aged from 7 to 12:44 males aged 10.65 and 44 females aged 9. 55, while those of 50 normalities were composed of 25 male and 25 female aged 10.9 respectively. In order to analyze growth proportion and sexual differences, twins were divided into 3 groups according to two year age intervals and the author compared male with female in 3 groups. For the purpose of observing similarities and differences in twins and normalities by sex, total twins were compared with normalities. The obtained results were as follows: 1. There was no difference in craniofacial complex between twins and normalities. 2. In general, the measurements of male were larger than those of female in both twins and normalities, but there were no statistical significances of sexual differences in both groups. 3. The growth proportion of mandible by aging was larger than that of face in twins. 4. The growth pattern of gonial angle showed slight reducing tendency in twin by aging. 5. There was little difference in the growth proportion of both male and female.

  9. Alcohol percutaneous neurolysis of the sphenopalatine ganglion in the management of refractory cranio-facial pain

    Energy Technology Data Exchange (ETDEWEB)

    Kastler, Adrian [Grenoble University Hospital, Neuroradiology Department, Grenoble (France); Franche Comte University, I4S Laboratory, EA4268, IFR133, Besancon (France); Cadel, Gilles; Gory, Guillaume [Franche Comte University, I4S Laboratory, EA4268, IFR133, Besancon (France); Comte, Alexandre [University Hospital Besancon, Functional Imaging Research Department, Besancon (France); Piccand, Veronique [University Hospital Jean Minjoz, Pain Evaluation and Treatment Unit, Besancon (France); Tavernier, Laurent [Franche Comte University, I4S Laboratory, EA4268, IFR133, Besancon (France); University Hospital Jean Minjoz, Head and Neck Surgery-Otolaryngology Unit, Besancon (France); Kastler, Bruno [Franche Comte University, I4S Laboratory, EA4268, IFR133, Besancon (France); University Hospital Jean Minjoz, Interventional Pain Management Unit, Besancon (France)

    2014-07-15

    The sphenopalatine ganglion (SPN) has been proven to be involved in various types of facial pain syndromes. Management of these cranio-facial pain syndromes can be challenging, and existing specific treatments are sometimes inefficient and may fail. The purpose of this study is to describe and evaluate alcohol SPN in the management of cranio-facial pain. Forty-two patients suffering from refractory facial pain who underwent 58 consecutive SPN were included in this study between 2000 and 2013. Patients were divided into three groups: group ''cluster headache'' (CH), group ''persistent idiopathic facial pain'' (PFIP), and group ''Other''. Pain was assessed using Visual Analogue Scale scores (measured immediately before and after procedure and at regular intervals following the procedure). Alcohol SPN was considered to be effective when pain relief was equal to or greater than 50 % and lasting for at least 1 month. All procedures were realized ambulatory under CT guidance and consisted of an injection of 1 ml of absolute alcohol. Overall efficacy rate of alcohol SPN was 67.2 %, with mean pain relief duration of 10.3 months. Procedure was graded either not painful or tolerable by patients in 64.2 %. Analysis showed a higher efficacy rate in the groups CH (76.5 %) and PFIP (85.7 %) compared to the group Other (40 %). No difference was found between groups regarding the recurrence rate. Alcohol SPN under CT guidance appears as a safe and effective treatment of refractory facial pain, especially in cases of cluster headache and persistent idiopathic facial pain. (orig.)

  10. A lateral cephalometric study of craniofacial variation in Korean child twins

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Rae; You, Dong Soo [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1974-11-15

    A study was performed to investigate the degree of similarities and differences in components of craniofacial complex between Korean twins and normal children by lateral cephalometric analysis. Dimensions of S-N, S-Ba, N-Ba, Go-Me, Ar-Go and Ar-Me were plotted against linear measurement and angles of N-S-Ba and gonial against angular measurement in twins and control groups. The lateral cephalograms of twin were composed of 88 twins aged from 7 to 12:44 males aged 10.65 and 44 females aged 9. 55, while those of 50 normalities were composed of 25 male and 25 female aged 10.9 respectively. In order to analyze growth proportion and sexual differences, twins were divided into 3 groups according to two year age intervals and the author compared male with female in 3 groups. For the purpose of observing similarities and differences in twins and normalities by sex, total twins were compared with normalities. The obtained results were as follows: 1. There was no difference in craniofacial complex between twins and normalities. 2. In general, the measurements of male were larger than those of female in both twins and normalities, but there were no statistical significances of sexual differences in both groups. 3. The growth proportion of mandible by aging was larger than that of face in twins. 4. The growth pattern of gonial angle showed slight reducing tendency in twin by aging. 5. There was little difference in the growth proportion of both male and female.

  11. Alcohol percutaneous neurolysis of the sphenopalatine ganglion in the management of refractory cranio-facial pain

    International Nuclear Information System (INIS)

    Kastler, Adrian; Cadel, Gilles; Gory, Guillaume; Comte, Alexandre; Piccand, Veronique; Tavernier, Laurent; Kastler, Bruno

    2014-01-01

    The sphenopalatine ganglion (SPN) has been proven to be involved in various types of facial pain syndromes. Management of these cranio-facial pain syndromes can be challenging, and existing specific treatments are sometimes inefficient and may fail. The purpose of this study is to describe and evaluate alcohol SPN in the management of cranio-facial pain. Forty-two patients suffering from refractory facial pain who underwent 58 consecutive SPN were included in this study between 2000 and 2013. Patients were divided into three groups: group ''cluster headache'' (CH), group ''persistent idiopathic facial pain'' (PFIP), and group ''Other''. Pain was assessed using Visual Analogue Scale scores (measured immediately before and after procedure and at regular intervals following the procedure). Alcohol SPN was considered to be effective when pain relief was equal to or greater than 50 % and lasting for at least 1 month. All procedures were realized ambulatory under CT guidance and consisted of an injection of 1 ml of absolute alcohol. Overall efficacy rate of alcohol SPN was 67.2 %, with mean pain relief duration of 10.3 months. Procedure was graded either not painful or tolerable by patients in 64.2 %. Analysis showed a higher efficacy rate in the groups CH (76.5 %) and PFIP (85.7 %) compared to the group Other (40 %). No difference was found between groups regarding the recurrence rate. Alcohol SPN under CT guidance appears as a safe and effective treatment of refractory facial pain, especially in cases of cluster headache and persistent idiopathic facial pain. (orig.)

  12. Disturbances in dental development and craniofacial growth in children treated with hematopoietic stem cell transplantation.

    Science.gov (United States)

    Vesterbacka, M; Ringdén, O; Remberger, M; Huggare, J; Dahllöf, G

    2012-02-01

    To investigate the correlation between age, degree of disturbances in dental development, and vertical growth of the face in children treated with hematopoietic stem cell transplantation (HSCT). 39 long-term survivors of HSCT performed in childhood and transplanted before the age of 12, at a mean age of 6.8±3.3 years. Panoramic and cephalometric radiographs were taken at a mean age of 16.2 years. For each patient two age- and sex-matched healthy controls were included. The area of three mandibular teeth was measured and a cephalometric analysis was performed. The mean area of the mandibular central incisor, first and second molar was significantly smaller in the HSCT group, and the vertical growth of the face was significantly reduced, especially in the lower third, compared to healthy controls. A statistically significant correlation between age at HSCT, degree of disturbances in dental development, and vertical growth of the face was found. Children subjected to pre-HSCT chemotherapy protocols had significantly more growth reduction in vertical craniofacial variables compared to children without pre-HSCT chemotherapy. Conditioning regimens including busulfan or total body irradiation had similar deleterious effects on tooth area reduction and craniofacial parameters. The younger the child is at HSCT, the greater the impairment in dental and vertical facial development. This supports the suggestion that the reduction in lower facial height found in SCT children mainly is a result of impaired dental development and that young age is a risk factor for more severe disturbances. © 2012 John Wiley & Sons A/S.

  13. Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves.

    Directory of Open Access Journals (Sweden)

    Philip R Buskohl

    Full Text Available Embryonic heart valve primordia (cushions maintain unidirectional blood flow during development despite an increasingly demanding mechanical environment. Recent studies demonstrate that atrioventricular (AV cushions stiffen over gestation, but the molecular mechanisms of this process are unknown. Transforming growth factor-beta (TGFβ and serotonin (5-HT signaling modulate tissue biomechanics of postnatal valves, but less is known of their role in the biomechanical remodeling of embryonic valves. In this study, we demonstrate that exogenous TGFβ3 increases AV cushion biomechanical stiffness and residual stress, but paradoxically reduces matrix compaction. We then show that TGFβ3 induces contractile gene expression (RhoA, aSMA and extracellular matrix expression (col1α2 in cushion mesenchyme, while simultaneously stimulating a two-fold increase in proliferation. Local compaction increased due to an elevated contractile phenotype, but global compaction appeared reduced due to proliferation and ECM synthesis. Blockade of TGFβ type I receptors via SB431542 inhibited the TGFβ3 effects. We next showed that exogenous 5-HT does not influence cushion stiffness by itself, but synergistically increases cushion stiffness with TGFβ3 co-treatment. 5-HT increased TGFβ3 gene expression and also potentiated TGFβ3 induced gene expression in a dose-dependent manner. Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter (SERT, resulted in complete cessation of TGFβ3 induced mechanical strengthening. Finally, systemic 5-HT administration in ovo induced cushion remodeling related defects, including thinned/atretic AV valves, ventricular septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in elevated remodeling gene expression and increased TGFβ signaling activity, supporting our ex-vivo findings. Collectively, these results highlight TGFβ/5-HT signaling as a potent mechanism for control of biomechanical

  14. A case of intracranial mesenchymal chondrosarcoma

    International Nuclear Information System (INIS)

    Hoshino, Masami; Tanji, Hiroyuki; Watanabe, Masakazu

    1981-01-01

    Intracranial mesenchymal chondrosarcoma is very rare, only 14 cases being reported in Europe and in the United States of America. Recently we experienced a case in which the follow-up indicating computed tomograms (CT) demonstrated interesting data on the radiosensitivity of this tumor. The patient, a 14-year-old female was admitted to our hospital with the complaint of left hemiplegia which had gradually progressed. CT revealed an area spreading upward from the right median base of the skull and consisted of two components showing (A) a density as high as that of calcium and (B) a density higher than that of surrounding brain tissue, but much lower than that of calcium. Temporoparietal craniotomy was performed to resect approximately one-half of the tumor. Histological finding revealed mesenchymal chondrosarcoma. The component-A was though to be a cartilaginous tissue, and-B to be an undifferentiated mesenchymal tissue. Postoperative irradiation of 7,000 rad was initiated. The effect of radiotherapy as seen on computed tomograms is as follows, (1) decrease in the volume of the tumor by 26%, (2) decrease in density and enhancement of the area which is considered to be the undifferentiated mesenchymal cells, (3) mild reduction of the area which is considered to be the caltilaginous tissue, and (4) a very high density of the entire tumor similar in degree to that of the bone one year later. These results suggested that radiotherapy is effective for this tumor. (author)

  15. Andrographolide suppresses epithelial mesenchymal transition by ...

    Indian Academy of Sciences (India)

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown.

  16. Mesenchymal stem cells in oral reconstructive surgery

    DEFF Research Database (Denmark)

    Jakobsen, C; Sørensen, J A; Kassem, M

    2013-01-01

    This study evaluated clinical outcomes following intraoperative use of adult mesenchymal stem cells (MSCs) in various oral reconstructive procedures. PubMed was searched without language restrictions from 2000 to 2011 using the search words stem cell, oral surgery, tissue engineering, sinus lift...

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  10. Influx mechanisms in the embryonic and adult rat choroid plexus

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

  11. Pathways in pluripotency and differentiation of embryonic cells

    NARCIS (Netherlands)

    du Puy, L.

    2010-01-01

    Pluripotency - the potential to differentiate into derivatives of the three embryonic germ layers endoderm, ectoderm and mesoderm - is the main characteristic of embryonic stem (ES) cells. ES cells are derived from the inner cell mass (ICM) of a pre-implantation blastocyst and can self-renew

  12. Comparison of the mouse Embryonic Stem cell Test, the rat Whole Embryo Culture and the Zebrafish Embryotoxicity Test as alternative methods for developmental toxicity testing of six 1,2,4-triazoles

    International Nuclear Information System (INIS)

    Jong, Esther de; Barenys, Marta; Hermsen, Sanne A.B.; Verhoef, Aart; Ossendorp, Bernadette C.; Bessems, Jos G.M.; Piersma, Aldert H.

    2011-01-01

    The relatively high experimental animal use in developmental toxicity testing has stimulated the search for alternatives that are less animal intensive. Three widely studied alternative assays are the mouse Embryonic Stem cell Test (EST), the Zebrafish Embryotoxicity Test (ZET) and the rat postimplantation Whole Embryo Culture (WEC). The goal of this study was to determine their efficacy in assessing the relative developmental toxicity of six 1,2,4-triazole compounds, flusilazole, hexaconazole, cyproconazole, triadimefon, myclobutanil and triticonazole. For this purpose, we analyzed effects and relative potencies of the compounds in and among the alternative assays and compared the findings to their known in vivo developmental toxicity. Triazoles are antifungal agents used in agriculture and medicine, some of which are known to induce craniofacial and limb abnormalities in rodents. The WEC showed a general pattern of teratogenic effects, typical of exposure to triazoles, mainly consisting of reduction and fusion of the first and second branchial arches, which are in accordance with the craniofacial malformations reported after in vivo exposure. In the EST all triazole compounds inhibited cardiomyocyte differentiation concentration-dependently. Overall, the ZET gave the best correlation with the relative in vivo developmental toxicities of the tested compounds, closely followed by the EST. The relative potencies observed in the WEC showed the lowest correlation with the in vivo developmental toxicity data. These differences in the efficacy between the test systems might be due to differences in compound kinetics, in developmental stages represented and in the relative complexity of the alternative assays.

  13. Rehabilitative treatment of cleft lip and palate: experience of the Hospital for Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP - Part 1: overall aspects

    Directory of Open Access Journals (Sweden)

    José Alberto de Souza Freitas

    2012-02-01

    Full Text Available Cleft lip and palate is the most common among craniofacial malformations and causes several esthetic and functional implications that require rehabilitation. This paper aims to generally describe the several aspects related to this complex pathology and the treatment protocol used by the Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC-USP along 40 years of experience in the treatment of individuals with cleft lip and palate.

  14. Predictability of hand skill and cognitive abilities from craniofacial width in right- and left-handed men and women: relation of skeletal structure to cerebral function

    OpenAIRE

    Dayi, Ertunc; Okuyan, Mukadder; Tan, Uner

    2002-01-01

    Recently, a family of homeobox genes involved in brain and craniofacial development was identified. In light of this genetic background, we hypothesized that some functional characteristics of human brain (hand skill, cognition) may be linked to some structural characteristics of human skull (e.g. craniofacial width) in humans. Hand preference was assessed by the Oldfield`s Handedness Questionaire. Hand skill was measured by Peg Moving Task. Face width was measured from the anteroposterior ce...

  15. Hyaluronic acid in the tail and limb of amphibians and lizards recreates permissive embryonic conditions for regeneration due to its hygroscopic and immunosuppressive properties.

    Science.gov (United States)

    Alibardi, Lorenzo

    2017-12-01

    The present review focuses on the role of hyaluronate (hyaluronic acid; HA) during limb and tail regeneration in amphibians and lizards mainly in relation to cells of the immune system. This non-sulfated glycosaminoglycan (GAG) increases in early stages of wound healing and blastema formation, like during limb or tail embryogenesis, when the immune system is still immature. The formation of a regenerating blastema occurs by the accumulation of mesenchymal cells displaying embryonic-like antigens and HA. This GAG adsorbs large amount of water and generates a soft tissue over 80% hydrated where mesenchymal and epithelial cells can move and interact, an obligatory passage for organ regeneration. GAGs and HA in particular rise to a high amount and coat plasma membranes of blastema cells forming a shield that likely impedes to the circulating immune cells to elicit an immune reaction against the embryonic-like antigens present on blastema cells. The evolution of limb-tail regeneration in amphibians dates back to the Devonian-Carboniferous, while tail regeneration in lizards is a more recent evolution process, possibly occurred since the Jurassic, which is unique among amniotes. Both processes are associated with the reactivation of proliferating embryonic programs that involve the upregulation of genes for Wnt, non-coding RNAs, and HA synthesis in an immune-suppress organ, the regenerative blastema. Failure of maintaining a lasting HA synthesis for the formation of a highly hydrated blastema leads to scarring, the common healing process of amniotes equipped with an efficient immune system. The study of amphibian and lizard regeneration indicates that attempts to stimulate organ regeneration in other vertebrates require the induction of a highly hydrated and immune-depressed, HA-rich environment, similar to the extracellular environment present during development. © 2017 Wiley Periodicals, Inc.

  16. Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4

    Directory of Open Access Journals (Sweden)

    Leprince Pierre

    2004-09-01

    Full Text Available Abstract Background Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. Results In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings and we report here that nestin-positive (but not nestin-negative mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1 this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2 anti-BMP4 antibodies inhibit the nestin-positive mesenchymal

  17. Isolation and cellular properties of mesenchymal cells derived from the decidua of human term placenta.

    Science.gov (United States)

    Kanematsu, Daisuke; Shofuda, Tomoko; Yamamoto, Atsuyo; Ban, Chiaki; Ueda, Takafumi; Yamasaki, Mami; Kanemura, Yonehiro

    2011-09-01

    The clinical promise of cell-based therapies is generally recognized, and has driven an intense search for good cell sources. In this study, we isolated plastic-adherent cells from human term decidua vera, called decidua-derived-mesenchymal cells (DMCs), and compared their properties with those of bone marrow-derived-mesenchymal stem cells (BM-MSCs). The DMCs strongly expressed the mesenchymal cell marker vimentin, but not cytokeratin 19 or HLA-G, and had a high proliferative potential. That is, they exhibited a typical fibroblast-like morphology for over 30 population doublings. Cells phenotypically identical to the DMCs were identified in the decidua vera, and genotyping confirmed that the DMCs were derived from the maternal components of the fetal adnexa. Flow cytometry analysis showed that the expression pattern of CD antigens on the DMCs was almost identical to that on BM-MSCs, but some DMCs expressed the CD45 antigen, and over 50% of them also expressed anti-fibroblast antigen. In vitro, the DMCs showed good differentiation into chondrocytes and moderate differentiation into adipocytes, but scant evidence of osteogenesis, compared with the BM-MSCs. Gene expression analysis showed that, compared with BM-MSCs, the DMCs expressed higher levels of TWIST2 and RUNX2 (which are associated with early mesenchymal development and/or proliferative capacity), several matrix metalloproteinases (MMP1, 3, 10, and 12), and cytokines (BMP2 and TGFB2), and lower levels of MSX2, interleukin 26, and HGF. Although DMCs did not show the full multipotency of BM-MSCs, their higher proliferative ability indicates that their cultivation would require less maintenance. Furthermore, the use of DMCs avoids the ethical concerns associated with the use of embryonic tissues, because they are derived from the maternal portion of the placenta, which is otherwise discarded. Thus, the unique properties of DMCs give them several advantages for clinical use, making them an interesting and

  18. Medicina regenerativa: Células madre embrionarias y adultas Regenerative medicine: Embryonic and adult stem cells

    Directory of Open Access Journals (Sweden)

    Porfirio Hernández Ramírez

    2004-12-01

    Full Text Available En los últimos años ha surgido una nueva rama de la medicina denominada medicina regenerativa, basada fundamentalmente en los nuevos conocimientos sobre las células madre y en su capacidad de convertirse en células de diferentes tejidos. Las células madre se clasifican en embrionarias y somáticas o adultas. Durante varios años se consideró que la célula madre hematopoyética era la única célula en la médula ósea con capacidad generativa. Sin embargo, estudios recientes han mostrado que la composición de la médula ósea es más compleja, pues en ella se ha identificado un grupo heterogéneo de células madre adultas, entre las que se encuentran las: hematopoyéticas, mesenquimales (estromales, población lateral, células progenitoras adultas multipotentes (MAPC. Varios estudios han sugerido que la potencialidad de algunos tipos de células madre adultas es mayor de lo esperado, pues han mostrado en determinadas condiciones capacidad para diferenciarse en células de diferentes linajes, lo que las acercan a la potencialidad de las células embrionarias. Esto ha creado nuevas perspectivas para el tratamiento de diferentes enfermedades con células madre adultas, lo que inicialmente se pensaba solo podía hacerse con las embrionariasIn the last few years, there has emerged a new branch of medicine called regenerative medicine based mainly on the new knowledge about stem cells and their capacity to turn into cells of different tissues. Stem cells are classified into embryonic cells and somatic or adult cells. For many years, it was believed that hematopoietic stem cell was the only one with regenerative capacity in the bone-marrow. However, recent studies have shown that the composition of the bone marrow is more complex an heterogeneous group of adult stem cells such as hematopoietic, mesenchymal (stromal, lateral population and multipotent adult progenitor cells have been identified there. Several studies suggested that the

  19. Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies

    DEFF Research Database (Denmark)

    Wright, A; Andrews, N; Bardsley, K

    2011-01-01

    The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the 'undifferentiated state...... of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment....... and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic biochemistry and reactivity in immunohistochemistry of testicular germ cell tumours. Our data reveal a range...

  20. Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis

    International Nuclear Information System (INIS)

    Ji, Jiayao; Li, Qinggang; Xie, Yuansheng; Zhang, Xueguang; Cui, Shaoyuan; Shi, Suozhu; Chen, Xiangmei

    2012-01-01

    Highlights: ► Overexpression of Robo2 caused reduced UB branching and glomerular number. ► Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. ► No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. ► Overexpression of Robo2 affected MM cells migration and caused UB deficit. ► The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2–Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2–Robo2 signaling is also important for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that overexpression of Robo2 by microinjection in embryonic kidneys is an effective approach to study the function of Robo2.

  1. Human embryonic stem cells: preclinical perspectives

    Directory of Open Access Journals (Sweden)

    Sarda Kanchan

    2008-01-01

    Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

  2. Epigenetic control of embryonic stem cell fate

    DEFF Research Database (Denmark)

    Christophersen, Nicolaj Strøyer; Helin, Kristian

    2010-01-01

    Embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and are pluripotent, as they are able to differentiate into all cell types of the adult organism. Once established, the pluripotent ES cells can be maintained under defined culture conditions, but can also...... be induced rapidly to differentiate. Maintaining this balance of stability versus plasticity is a challenge, and extensive studies in recent years have focused on understanding the contributions of transcription factors and epigenetic enzymes to the "stemness" properties of these cells. Identifying...... the molecular switches that regulate ES cell self-renewal versus differentiation can provide insights into the nature of the pluripotent state and enhance the potential use of these cells in therapeutic applications. Here, we review the latest models for how changes in chromatin methylation can modulate ES cell...

  3. Embryonic stem cells in pig and cattle

    DEFF Research Database (Denmark)

    Maddox-Hyttel, Poul; Wolf, Xenia Asbæk; Rasmussen, Mikkel Aabech

    2007-01-01

    Porcine and bovine cell lines derived from the inner cell mass (ICM) or epiblasts of blastocysts have been maintained over extended periods of time and characterized by morphology, identification of some stem cell markers and, in few cases, by production of chimaeric offspring. However, germ line...... transmission in chimaeras has never been obtained. Due to this incomplete characterization of the cell lines, the expression embryonic stem (ES)-like cells is presently used in pig and cattle. The ICM or epiblast can be isolated from the blastocyst by whole blastocyst culture, mechanical isolation......, or immunosurgery, and they are generally cultured on feeder cells. The resulting ES-like cells may be differentiated in vivo by chimaera and teratoma formation or in vitro by embryoid body formation and monolayer induction. It is likely that more well characterized and stable porcine and bovine ES cell lines...

  4. New gene targets for glucagon-like peptide-1 during embryonic development and in undifferentiated pluripotent cells.

    Science.gov (United States)

    Sanz, Carmen; Blázquez, Enrique

    2011-09-01

    In humans, glucagon-like peptide (GLP-1) functions during adult life as an incretin hormone with anorexigenic and antidiabetogenic properties. Also, the therapeutic potential of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and in bolstering the maintenance of human mesenchymal stem cell (hMSC) stores by promoting the proliferation and cytoprotection of hMSC seems to be relevant. Since these observations suggest a role for GLP-1 during developmental processes, the aim of the present work was to characterize GLP-1 in early development as well as its gene targets in mouse embryonic stem (mES) cells. Mouse embryos E6, E8, and E10.5 and pluripotent mES were used for the inmunodetection of GLP-1 and GLP-1 receptor. Quantitative real-time PCR was used to determine the expression levels of GLP-1R in several tissues from E12.5 mouse embryos. Additionally, GLP-1 gene targets were studied in mES by multiple gene expression analyses. GLP-1 and its receptors were identified in mES and during embryonic development. In pluripotent mES, GLP-1 modified the expression of endodermal, ectodermal, and mesodermal gene markers as well as sonic hedgehog, noggin, members of the fibroblast and hepatic growth factor families, and others involved in pancreatic development. Additionally, GLP-1 promoted the expression of the antiapoptotic gene bcl2 and at the same time reduced proapoptotic caspase genes. Our results indicate that apart from the effects and therapeutic benefits of GLP-1 in adulthood, it may have additional gene targets in mES cells during embryonic life. Furthermore, the pathophysiological implications of GLP-1 imbalance in adulthood may have a counterpart during development.

  5. Human embryonic stem cells and microenvironment

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2014-09-01

    Full Text Available Human embryonic stem cells (hESCs possess a great potential in the field of regenerative medicine by their virtue of pluripotent potential with indefinite proliferation capabilities. They can self renew themselves and differentiate into three embryonic germ layers. Although they are conventionally grown on mitotically inactivated mouse feeder cells, there are in vitro culture systems utilizing feeder cells of human origin in order to prevent cross-species contamination. Recently established in vitro culture systems suggested that direct interaction with feeder cells is not necessary but rather attachment to a substrate is required to ensure long-term, efficient hESC culture in vitro. This substrate is usually composed of a mixture of extracellular matrix components representing in vivo natural niche. In hESC biology, the mechanism of interaction of hESCs with extracellular matrix molecules remained insufficiently explored area of research due to their transient nature of interaction with the in vivo niche. However, an in vitro culture system established using extracellular matrix molecules may provide a safer alternative to culture systems with feeder cells while paving the way to Good Manufacturing Practice-GMP production of hESCs for therapeutic purposes. Therefore, it is essential to study the interaction of extracellular matrix molecules with hESCs in order to standardize in vitro culture systems for large-scale production of hESCs in a less labor-intensive way. This would not only provide valuable information regarding the mechanisms that control pluripotency but also serve to dissect the molecular signaling pathways of directed differentiation for prospective therapeutic applications in the future. J Clin Exp Invest 2014; 5 (3: 486-495

  6. Influence of craniofacial and upper spine morphology on mandibular advancement device treatment outcome in patients with obstructive sleep apnoea

    DEFF Research Database (Denmark)

    Svanholt, Palle; Petri, Niels; Wildschiødtz, Gordon

    2015-01-01

    Summary BACKGROUND/OBJECTIVES: The aim of the study was to assess cephalometric predictive markers in terms of craniofacial morphology including posterior cranial fossa and upper spine morphology for mandibular advancement device (MAD) treatment outcome in patients with obstructive sleep apnoea...... patients and the no success treatment group of 19 patients. Before MAD treatment lateral cephalograms were taken and analyses of the craniofacial morphology including the posterior cranial fossa and upper spine morphology were performed. Differences between the groups were analysed by Fisher's exact test......, t-test, and multiple regression analysis. RESULTS: Upper spine morphological deviations occurred non-significantly in 25 per cent in the success treatment group and in 42.1 per cent in the no success treatment group. Body mass index (BMI; P

  7. Multimodal physiotherapy treatment based on a biobehavioral approach for patients with chronic cervico-craniofacial pain: a prospective case series.

    Science.gov (United States)

    Marcos-Martín, Fernando; González-Ferrero, Luis; Martín-Alcocer, Noelia; Paris-Alemany, Alba; La Touche, Roy

    2018-01-17

    The purpose of this prospective case series was to observe and describe changes in patients with chronic cervico-craniofacial pain of muscular origin treated with multimodal physiotherapy based on a biobehavioral approach. Nine patients diagnosed with chronic myofascial temporomandibular disorder and neck pain were treated with 6 sessions over the course of 2 weeks including: (1) orthopedic manual physiotherapy (joint mobilizations, neurodynamic mobilization, and dynamic soft tissue mobilizations); (2) therapeutic exercises (motor control and muscular endurance exercises); and (3) patient education. The outcome measures of craniofacial (CF-PDI) and neck disability (NDI), kinesiophobia (TSK-11) and catastrophizing (PCS), and range of cervical and mandibular motion (ROM) and posture were collected at baseline, and at 2 and 14 weeks post-baseline. Compared to baseline, statistically significant (p posture were observed following a multimodal physiotherapy treatment based on a biobehavioral approach.

  8. Original Solution for Middle Ear Implant and Anesthetic/Surgical Management in a Child with Severe Craniofacial Dysmorphism

    Directory of Open Access Journals (Sweden)

    Giovanni Bianchin

    2015-01-01

    Full Text Available We describe the novel solution adopted in positioning middle ear implant in a child with bilateral congenital aural atresia and craniofacial dysmorphism that have posed a significant challenge for the safe and correct management of deafness. A five-year-old child, affected by a rare congenital disease (Van Maldergem Syndrome, suffered from conductive hearing loss. Conventional skin-drive bone-conduction device, attached with a steel spring headband, has been applied but auditory restoration was not optimal. The decision made was to position Vibrant Soundbridge, a middle ear implant, with an original surgical application due to hypoplasia of the tympanic cavity. Intubation procedure was complicated due to child craniofacial deformities. Postoperative hearing rehabilitation involved a multidisciplinary team, showing improved social skills and language development.

  9. Indian hedgehog regulates intestinal stem cell fate through epithelial-mesenchymal interactions during development

    NARCIS (Netherlands)

    Kosinski, C.; Stange, D.E.; Xu, C.; Chan, A.S.; Ho, C.; Yuen, S.T.; Mifflin, R.C.; Powell, D.W.; Clevers, H.; Leung, S.Y.; Chen, X.N.

    2010-01-01

    BACKGROUND & AIMS: Intestinal stem cells (ISCs) are regulated by the mesenchymal environment via physical interaction and diffusible factors. We examined the role of Indian hedgehog (Ihh) in mesenchymal organization and the mechanisms by which perturbations in epithelial-mesenchymal interactions

  10. Use of RUNX2 Expression to Identify Osteogenic Progenitor Cells Derived from Human Embryonic Stem Cells

    Science.gov (United States)

    Zou, Li; Kidwai, Fahad K.; Kopher, Ross A.; Motl, Jason; Kellum, Cory A.; Westendorf, Jennifer J.; Kaufman, Dan S.

    2015-01-01

    Summary We generated a RUNX2-yellow fluorescent protein (YFP) reporter system to study osteogenic development from human embryonic stem cells (hESCs). Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP+ cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells. In vivo studies demonstrate the hESC-derived YFP+ cells can repair a calvarial defect in immunodeficient mice. Using the engineered hESCs, we monitored the osteogenic development and explored the roles of osteogenic supplements BMP2 and FGF9 in osteogenic differentiation of these hESCs in vitro. Taken together, this reporter system provides a novel system to monitor the osteogenic differentiation of hESCs and becomes useful to identify soluble agents and cell signaling pathways that mediate early stages of human bone development. PMID:25680477

  11. Use of RUNX2 Expression to Identify Osteogenic Progenitor Cells Derived from Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Li Zou

    2015-02-01

    Full Text Available We generated a RUNX2-yellow fluorescent protein (YFP reporter system to study osteogenic development from human embryonic stem cells (hESCs. Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP+ cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells. In vivo studies demonstrate the hESC-derived YFP+ cells can repair a calvarial defect in immunodeficient mice. Using the engineered hESCs, we monitored the osteogenic development and explored the roles of osteogenic supplements BMP2 and FGF9 in osteogenic differentiation of these hESCs in vitro. Taken together, this reporter system provides a novel system to monitor the osteogenic differentiation of hESCs and becomes useful to identify soluble agents and cell signaling pathways that mediate early stages of human bone development.

  12. In vitro differentiation and maturation of mouse embryonic stem cells into hepatocytes

    International Nuclear Information System (INIS)

    Ishii, Takamichi; Yasuchika, Kentaro; Fujii, Hideaki; Hoppo, Toshitaka; Baba, Shinji; Naito, Masato; Machimoto, Takafumi; Kamo, Naoko; Suemori, Hirofumi; Nakatsuji, Norio; Ikai, Iwao

    2005-01-01

    It is difficult to induce the maturation of embryonic stem (ES) cells into hepatocytes in vitro. We previously reported that Thy1-positive mesenchymal cells derived from the mouse fetal liver promote the maturation of hepatic progenitor cells. Here, we isolated alpha-fetoprotein (AFP)-producing cells from mouse ES cells for subsequent differentiation into hepatocytes in vitro by coculture with Thy1-positive cells. ES cells expressing green fluorescent protein (GFP) under the control of an AFP promoter were cultured under serum- and feeder layer-free culture conditions. The proportion of GFP-positive cells plateaued at 41.6 ± 12.2% (means ± SD) by day 7. GFP-positive cells, isolated by flow cytometry, were cultured in the presence or absence of Thy1-positive cells as a feeder layer. Isolated GFP-positive cells were stained for AFP, Foxa2, and albumin. The expression of mRNAs encoding tyrosine amino transferase, tryptophan 2,3-dioxygenase, and glucose-6-phosphatase were only detected following coculture with Thy1-positive cells. Following coculture with Thy1-positive cells, the isolated cells produced and stored glycogen. Ammonia clearance activity was also enhanced following coculture. Electron microscopic analysis indicated that the cocultured cells exhibited the morphologic features of mature hepatocytes. In conclusion, coculture with Thy1-positive cells in vitro induced the maturation of AFP-producing cells isolated from ES cell cultures into hepatocytes

  13. Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development.

    Directory of Open Access Journals (Sweden)

    Anita M Quintana

    Full Text Available There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions. Moreover, we utilized loss of function analysis and pharmacological inhibition to determine the extent of sonic hedgehog (Shh signaling in animals with aberrant cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway, results in craniofacial abnormalities via defects in cranial neural crest cell differentiation. Furthermore targeted pharmacological inhibition of the cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf, but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants. These data raise the possibility that deficiencies in cholesterol modulate chondrocyte differentiation by a combination of Shh independent and Shh dependent mechanisms. Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms.

  14. Expression of Dlx-5 and Msx-1 in Craniofacial Skeletons and Ilia of Rats Treated With Zoledronate.

    Science.gov (United States)

    Xuan, Bin; Yang, Pan; Wu, Shichao; Li, Lin; Zhang, Jian; Zhang, Wenyi

    2017-05-01

    Because of the different embryologic origins of the craniofacial skeleton and ilium, differences in gene expression patterns have been observed between the jaw bones and ilium. Distal-less homeobox (Dlx) genes and Msh homeobox genes, particularly Dlx-5 and Msx-1, play major roles in cell differentiation and osteogenesis. The purpose of this study was to investigate the effects of zoledronate (ZOL) on the craniofacial skeleton and ilium by detecting changes in Dlx-5 and Msx-1 expression at both the protein and messenger RNA levels. A total of 24 female Sprague-Dawley rats were randomly divided into 2 groups: ZOL group (n = 12), in which the rats were injected intraperitoneally with zoledronic acid for 12 weeks, and control group (n = 12), in which the rats were injected with saline solution for 12 weeks. By use of immunohistochemistry, Western blotting, and real-time reverse transcription polymerase chain reaction, the expression levels of Dlx-5 and Msx-1 in the craniofacial skeleton (including the maxilla, mandible, and parietal bone) and ilium were examined. Dlx-5 expression in the maxilla and mandible was increased at the protein and messenger RNA levels in the ZOL group compared with the control group (P Msx-1 expression in the maxilla and mandible was decreased in the ZOL group (P Msx-1 expression in the ilium was decreased in the ZOL group (P Msx-1 expression in the parietal bone was observed between the 2 groups (P > .05). Site-specific differences in the effects of ZOL on the craniofacial skeleton and ilium could be explained by differently altered tendencies in Dlx-5 and Msx-1 expression. The jaw bones were more susceptible to the effects of ZOL than the parietal bone and ilium. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Original Solution for Middle Ear Implant and Anesthetic/Surgical Management in a Child with Severe Craniofacial Dysmorphism

    OpenAIRE

    Giovanni Bianchin; Lorenzo Tribi; Aronne Reverzani; Patrizia Formigoni; Valeria Polizzi

    2015-01-01

    We describe the novel solution adopted in positioning middle ear implant in a child with bilateral congenital aural atresia and craniofacial dysmorphism that have posed a significant challenge for the safe and correct management of deafness. A five-year-old child, affected by a rare congenital disease (Van Maldergem Syndrome), suffered from conductive hearing loss. Conventional skin-drive bone-conduction device, attached with a steel spring headband, has been applied but auditory restoration ...

  16. Craniofacial morphology of children with complete unilateral cleft lip and palate following labioplasty and palatoplasty

    Directory of Open Access Journals (Sweden)

    Sigit Handoko Utomo

    2012-06-01

    Full Text Available Background: A complete unilateral cleft lip and palate generally results in asymmetry of the midface. The lack of continuity in the perilabial musculature through the midline contributes to a malpositioning of the underlying osseus structures which are often underdeveloped. Purpose: The purpose of this study was to determine whether there are differences in the craniofacial morphology among children with complete unilateral cleft lip and palate following labioplasty and palatoplasty as compared with children without cleft lip and palate at the same pubertal age. Methods: A series of 14 consecutively treated subjects with complete unilateral cleft lip and palate following labioplasty and palatoplasty were compared with 14 pubertal stage-matched controls with normal craniofacial structure. Pubertal stage was determined with cervical vertebral maturation (CVM method improved by Baccetti et al, 2002. Lateral cephalograms were used for comparison. An unpaired t-test was run for 14 subjects with complete unilateral cleft lip and palate and 14 normal subjects. Results: There were significant cephalometric differences in anterior cranial base length (p = .002, cranial base length (p = .001, maxillary length (p = .000, mandibular length (p = .000, mandibular ramus height (p = .000, mandibular body length (p = .002, and upper anterior face height (p = .004. There was no significant cephalometric difference in posterior cranial base length (p = .051, lower anterior face height (p = .206, posterior face height (p = .865, growth pattern/ facial type (p = .202. Conclusion: There were craniofacial morphology differences between children with complete unilateral cleft lip and palate post labioplasty and palatoplasty and children without cleft lip and palate at the age of pubertal. Children with complete unilateral cleft lip and palate post labioplasty and palatoplasty had shorter length of the anterior cranial base, cranial base, maxilla, mandible, mandibular

  17. Stepwise development of hematopoietic stem cells from embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kenji Matsumoto

    Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

  18. Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

    Science.gov (United States)

    Arce-Estrada, Gabriel Emmanuel; Gómez-Toscano, Valeria; Cedillo-Peláez, Carlos; Sesman-Bernal, Ana Luisa; Bosch-Canto, Vanessa; Mayorga-Butrón, José Luis; Vargas-Villavicencio, José Antonio; Correa, Dolores

    2017-07-03

    We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. A two-month-old male had a twin in utero who disappeared between the 7 th and the 14 th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

  19. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Science.gov (United States)

    Ignatius, Myron S; Unal Eroglu, Arife; Malireddy, Smitha; Gallagher, Glen; Nambiar, Roopa M; Henion, Paul D

    2013-01-01

    The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  20. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

    Full Text Available The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.