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Sample records for extraskeletal mesenchymal chondrosarcoma

  1. Extraskeletal mesenchymal chondrosarcoma of the carotid space: A case report

    International Nuclear Information System (INIS)

    Huh, Sun; Hong, Hyun Sook; Kwak, Jeong Ja; Park, Ji Sang; Jeong, Sun Hye

    2015-01-01

    Chondrosarcoma is a commonly encountered malignant cartilaginous tumor. However, only 1% of chondrosarcomas arise in the extraskeletal region. The pathologic types of this tumor include mesenchymal, myxoid, and low grade. A mesenchymal chondrosarcoma is a rare, highly malignant cartilaginous tumor that is rarely encountered, and it shows similar imaging features to other malignant soft-tissue tumors. Here, we report a mesenchymal chondrosarcoma presenting as a palpable mass in the neck, arising in the carotid space, which is also known as the retrostyloid parapharyngeal space.

  2. Primary Extraskeletal Mesenchymal Chondrosarcoma Arising from the Pancreas

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    Oh, Bae Geun; Han, Yoon Hee; Lee, Byung Hoon; Kim, Su Young; Hwang, Yoon Joon; Seo, Jung Wook; Kim, Yong Hoon; Cha, Soon Joo; Hur, Gham; Joo, Mee [Inje University, School of Medicine, Goyang (Korea, Republic of)

    2007-12-15

    The CT scans showed a heterogeneously enhancing necrotic mass with numerous areas of coarse calcification, and this was located in the left side of the retroperitoneal space and involved the body and tail of the pancreas. Portal venography via the celiac axis also showed invasion of the splenic vein. It represents approximately 1% of all chondrosarcomas and it carries a poor prognosis. It can occur in extraskeletal locations and mainly in the soft tissues of the orbit, the cranial and spinal meningeal coverings and the lower limbs. To the best of our knowledge, there has been no reported case of primary extraskeletal mesenchymal chondrosarcoma of the pancreas. Only two instances of metastatic chondrosarcomas in the pancreas have been reported in the literature. We report here on a case of primary mesenchymal chondrosarcoma arising from the pancreas in a 41-year-old man. In summary, we present here a case of primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas. Radiologically, it manifested as a necrotic soft tissue mass with chondroid calcifications.

  3. Primary Extraskeletal Mesenchymal Chondrosarcoma Arising from the Pancreas

    International Nuclear Information System (INIS)

    Oh, Bae Geun; Han, Yoon Hee; Lee, Byung Hoon; Kim, Su Young; Hwang, Yoon Joon; Seo, Jung Wook; Kim, Yong Hoon; Cha, Soon Joo; Hur, Gham; Joo, Mee

    2007-01-01

    The CT scans showed a heterogeneously enhancing necrotic mass with numerous areas of coarse calcification, and this was located in the left side of the retroperitoneal space and involved the body and tail of the pancreas. Portal venography via the celiac axis also showed invasion of the splenic vein. It represents approximately 1% of all chondrosarcomas and it carries a poor prognosis. It can occur in extraskeletal locations and mainly in the soft tissues of the orbit, the cranial and spinal meningeal coverings and the lower limbs. To the best of our knowledge, there has been no reported case of primary extraskeletal mesenchymal chondrosarcoma of the pancreas. Only two instances of metastatic chondrosarcomas in the pancreas have been reported in the literature. We report here on a case of primary mesenchymal chondrosarcoma arising from the pancreas in a 41-year-old man. In summary, we present here a case of primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas. Radiologically, it manifested as a necrotic soft tissue mass with chondroid calcifications

  4. Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma

    International Nuclear Information System (INIS)

    Morioka, Hideo; Takahashi, Shunji; Araki, Nobuhito; Sugiura, Hideshi; Ueda, Takafumi; Takahashi, Mitsuru; Yonemoto, Tsukasa; Hiraga, Hiroaki; Hiruma, Toru; Kunisada, Toshiyuki; Matsumine, Akihiko; Susa, Michiro; Nakayama, Robert; Nishimoto, Kazumasa; Kikuta, Kazutaka; Horiuchi, Keisuke; Kawai, Akira

    2016-01-01

    Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study. Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review. The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4–not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3–1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10.4–26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive. This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were better

  5. Extraskeletal myxoid chondrosarcoma of the neck

    NARCIS (Netherlands)

    Oh, Y.J.; Yang, I.; Yoon, D.Y.; Cho, S.J.; Lee, Y.; Woo, J.Y.; Jung, A.Y.; Hong, H.S.; Jeh, S.K.

    2013-01-01

    Extraskeletal myxoid chondrosarcoma is a rare malignant soft-tissue tumour that is typically in the deep soft tissues of the lower extremity. The tumour is usually a well-defined, multinodular soft-tissue mass without calcifications. A 62-year-old woman with a history of nasopharyngeal cancer

  6. Curious case of extraskeletal myxoid chondrosarcoma

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    Sushilkumar Satish Gupta

    2017-01-01

    Full Text Available Extraskeletal myxoid chondrosarcomas (EMC are a rare entity of soft tissue tumors that have slow growth with metastatic potential. We discuss here a case of EMC presenting with right upper extremity pain and hemoptysis. Computed tomography scans chest showed diffuse metastatic numerous lung nodules bilaterally. Biopsy confirmed the diagnosis of the tumor. Chemotherapy was a bigger challenge for our patient due to sparse research and data in the literature about the disease.

  7. MRI features of extraskeletal myxoid chondrosarcoma

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    Tateishi, Ukihide; Arai, Yasuaki [National Cancer Center Hospital, Division of Diagnostic Radiology, Tokyo (Japan); Hasegawa, Tadashi [Sapporo Medical University School of Medicine, Department of Clinical Pathology, Sapporo (Japan); Nojima, Takayuki [Kanazawa Medical University, Department of Pathology, Ishikawa (Japan); Takegami, Tsutomu [Kanazawa Medical University, Medical Research Institute, Ishikawa (Japan)

    2006-01-01

    To describe the MRI features of extraskeletal myxoid chondrosarcoma in comparison with clinicopathologic findings. The study comprised 12 male subjects and seven female subjects with a mean age of 53 years (range 16-76 years). MRI findings, evaluated by two radiologists with agreement by consensus, were compared for histopathologic features. The tumor size ranged from 2.0 cm to 20.0 cm (mean 8.9 cm). Fusion gene transcripts could be detected in 13 (68%) of the 19 cases: EWS-CHN in nine cases, TAF2N-CHN in three, and TFG-TCH in one. There were six fusion-negative cases. Signal characteristics on T1-weighted and T2-weighted MR images were non-specific with regard to each cytogenetic variant. Peripheral enhancement was seen more frequently in tumors with the EWS-CHN variant than in those with other cytogenetic variants. The characteristic pattern of enhancement corresponded to the presence of fibrous septa and peripheral areas of high cellularity within lobules, by correlation with pathologic findings. All cases with TAF2N-CHN or TFG-TCH variants showed invasion of extracompartmental structure, bone, or vessels. Extraskeletal myxoid chondrosarcoma is an uncommon soft-tissue malignancy that may be recognized by MRI features of multi-lobular soft-tissue mass often invading extracompartmental, bony, and vascular structures. (orig.)

  8. Pulmonary extraskeletal myxoid chondrosarcoma: A case report and literature review

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    Ricardo Balanzá, MD

    2016-01-01

    Conclusion: EMC is an intermediate-grade neoplasm, characterized by a long clinical course with high potential for local recurrence and distant metastasis. Treatment for EMC is surgical and non-surgical treatment is reserved for recurrence or metastatic disease. Pulmonary extraskeletal myxoid chondrosarcoma is a rare neoplasm with only isolated case reports found in the literature.

  9. Extraskeletal Myxoid Chondrosarcoma with Small Bowel Metastasis Causing Bowel Obstruction

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    Ernesto Bustinza-Linares

    2012-01-01

    Full Text Available A 28-year-old female with history of chest wall extraskeletal myxoid chondrosarcoma (EMC presented to the emergency department complaining of two weeks of lightheadedness and fatigue. Laboratories showed hemoglobin of 7.6 g/dL and a positive hemoccult test. Upper and lower endoscopies were unremarkable, and the patient was discharged after blood transfusion. The next day she returned to the ED with left-sided weakness and perioral numbness. Brain CT scan revealed a 6 cm right frontal mass with midline shift and edema that required urgent craniotomy with resection of a hemorrhagic tumor. The patient continued dropping her hemoglobin, and CT scans showed a rounded 3 cm small bowel mass in the mid ileum. Repeat upper endoscopy revealed a 2 × 2 cm ulcerated mass in the fourth portion of the duodenum. The patient was taken to the operating room and was found to have two lesions; one in the distal duodenum and a second one in the mid ileum causing small bowel intussusception. Pathology was consistent with metastatic EMC grade 2/3, involving the bowel and mesenteric fat. Extraskeletal myxoid chondrosarcoma (EMC is a rare soft-tissue sarcoma with unique features that distinguishes, it from other sarcomas. It has been often described as a low-grade sarcoma although there are certain characteristics like high mitotic activity and the presence of focal regions of Ki67 staining above 25% that correlate with aggressive behavior of the tumor. This is the first case of EMC metastatic to the small bowel to be reported to the medical community.

  10. 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

  11. Clinical-radiomorphological peculiarities of mesenchymal chondrosarcomas

    International Nuclear Information System (INIS)

    Korolev, V.I.

    1987-01-01

    Seven patients with mesenchymal chondrosarcoma that constituted 2% of all observable patients with chondrosarcoma were examined by the author. A complex of diagnostic methods of investigation used before operation (clinical, radiological, angiographic, radionuclider, cytologic, morphologic) permitted to diagnose mesenchymal chondrosarcoma only in one case. In other cases chondrosarcoma was diagnosed. Availability of nondifferentiated ''stroma'' or mesenchimal cells along with the differentiated cartilage areas is a characteristic property of mesenchymal chondrosarcoma. In a number of cases the cells are arranged around vessels and the tumor reminds hemangiopericytoma. Clinical and radiological tumor symptomatology depends on its morphological structure

  12. Mesenchymal chondrosarcoma: a case report.

    Science.gov (United States)

    Nguyen, Dang Vu; Muda, Ahmad Sobri; Yaacob, Yazmin

    2013-05-01

    Mesenchymal chondrosarcoma is a rare disease with poor prognosis. Treatment including wide or radical excision is very important. Radiotherapy and chemotherapy are additional treatment options, but no conclusive results for their efficacy have been shown until date. Imaging modalities can give important clues for diagnosis and management planning. Angioembolization before surgery could be useful as prophylaxis to control intraoperative bleeding, increasing the likelihood of complete resection.

  13. MRI of mesenchymal chondrosarcoma of the orbit: case report and review of the literature

    International Nuclear Information System (INIS)

    Shinaver, C.N.; Mafee, M.F.; Choi, K.H.

    1997-01-01

    Extraskeletal mesenchymal chondrosarcoma is a relatively uncommon entity, an orbital location being extremely rare. A review of the literature revealed 16 reported cases of primary orbital mesenchymal chondrosarcoma demonstrated by plain film and CT. To the best of our knowledge, the MRI features of orbital extraskeletal mesenchymal chondrosarcoma have not been previously reported. We present the case of an 18-year-old man with a 2-year history of progressive proptosis of the right eye who underwent CT, dynamic CT, MRI without and with gadolinium enhancement, and magnetic resonance angiography of the orbits. CT of orbital mesenchymal chondrosarcoma demonstrates a well-defined mass with multiple areas of fine and coarse calcification and shows moderate contrast enhancement. The noncalcified portions of the mass demonstrate signal intensity lower than or equal to gray matter on T1-weighted images and are isointense to the gray matter on T2-weighted images. Dynamic CT reveals delayed contrast enhancement. MRI has proven to be a valuable diagnostic tool in the diagnosis and differentiation of well-defined intraorbital masses. By a combination of CT and MRI, it appears mesenchymal chondrosarcoma can be differentiated from other intraorbital lesions, such as cavernous hemangioma, hemangiopericytoma, orbital amyloidosis and fibrous histiocytoma. (orig.). With 6 figs

  14. Extraskeletal myxoid chondrosarcoma in the lung: asymptomatic lung mass with severe anemia

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    Zhou Qianjun

    2012-08-01

    Full Text Available Abstract Extraskeletal myxoid chondrosarcoma (EMC is a rare soft-tissue sarcoma, which primarily occurs deep in the extremities, especially in skeletal muscle, or tendon. EMC of the pleura has been described, however, no case of primary EMC arising from lung has been previously reported. We describe herein, a 51-year-old Asian female initially manifested with signs of severe anemia who presented with a lung mass unrelated to pleura that was morphologically typical EMC, with strong immunoreactivity for vimentin and NSE. Two weeks after resection, the anemia was cured. The patient continued with follow-up, without sign of abnormality 32 months after operation. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2882199847396682

  15. 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)

  16. Mesenchymal chondrosarcoma of the right buccal region: A case report and review of the literature.

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    Yu, Lijiang; Li, Mingliang; Lin, Runtai; Mu, Yue; Zhao, Jizhi

    2014-12-01

    Extraskeletal mesenchymal chondrosarcoma (EMCS) is a rare malignant cartilaginous tumor arising from the soft tissues. The most common areas of extraskeletal origin are the lower extremities, the orbits and the central nervous system, among others. In this study, the case of primary EMCS arising from the right buccal region in a 26-year old female is presented. Histological and immunohistochemical analysis confirmed the diagnosis of EMCS. Subseqently, the patient was treated with radical surgery, but declined chemotherapy or radiotherapy, which was recommended. One year after surgery, no recurrence had been identified in the patient. To the best of our knowledge, only one case of primary EMCS of the buccal region has been reported previously. In the current study, a case of primary EMCS of the buccal region is presented.

  17. Mesenchymal Chondrosarcoma of Posterior Maxilla: Report of a ...

    African Journals Online (AJOL)

    Mesenchymal chondrosarcomas (MCs) are infrequent, slow‑growing malignant tumors of head and neck region affecting both bone and soft tissues. It represents approximately 1% of all chondrosarcomas. They usually occur in the middle aged individuals, but rarely seen in young patients. It is commonly found in the ribs ...

  18. [A rare variant of chondrosarcoma--mesenchymal chondrosarcoma of the scapula].

    Science.gov (United States)

    Modaev, V P; Lantsman, Iu V

    1987-01-01

    A rarely occurring tumor, mesenchymal chondrosarcoma of the shoulder blade, is described. The tumor, found in a 19-year-old male, consisted of two components; a typical chondrosarcoma showing a moderate degree of anaplasia, and a tumor tissue composed of poorly differentiated cells with large numbers of thin-walled vessels. The two tissues were separated from each other by connective-tissue elements, though cells of the second component were seen in places to pass into the tissue of hyalin cartilage. This variant of chondrosarcoma proved to be highly sensitive to chemotherapy, allowing considerable prolongation of the patient's survival.

  19. The TFG-TEC fusion gene created by the t(3;9) translocation in human extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional activator than TEC.

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    Lim, Bobae; Jun, Hee Jung; Kim, Ah-young; Kim, Sol; Choi, JeeHyun; Kim, Jungho

    2012-08-01

    The t(3;9)(q11-q12;q22) translocation associated with human extraskeletal myxoid chondrosarcomas results in a chimeric molecule in which the N-terminal domain (NTD) of the TFG (TRK-fused gene) is fused to the TEC (Translocated in Extraskeletal Chondrosarcoma) gene. Little is known about the biological function of TFG-TEC. Because the NTDs of TFG-TEC and TEC are structurally different, and the TFG itself is a cytoplasmic protein, the functional consequences of this fusion in extraskeletal myxoid chondrosarcomas were examined. The results showed that the chimeric gene encoded a nuclear protein that bound DNA with the same sequence specificity as the parental TEC protein. Comparison of the transactivation properties of TFG-TEC and TEC indicated that the former has higher transactivation activity for a known target reporter containing TEC-binding sites. Additional reporter assays for TFG (NTD) showed that the TGF (NTD) of TFG-TEC induced a 12-fold increase in the activation of luciferase from a reporter plasmid containing GAL4 binding sites when fused to the DNA-binding domain of GAL4, indicating that the TFG (NTD) of the TFG-TEC protein has intrinsic transcriptional activation properties. Finally, deletion analysis of the functional domains of TFG (NTD) indicated that the PB1 (Phox and Bem1p) and SPYGQ-rich region of TFG (NTD) were capable of activating transcription and that full integrity of TFG (NTD) was necessary for full transactivation. These results suggest that the oncogenic effect of the t(3;9) translocation may be due to the TFG-TEC chimeric protein and that fusion of the TFG (NTD) to the TEC protein produces a gain-of-function chimeric product.

  20. Mesenchymal chondrosarcoma of the sacrum: a case report and review of the literature.

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    Biagini, R; Orsini, U; Demitri, S; Ruggieri, P; Ferrari, S; Bertoni, F

    2000-01-01

    The authors present a case of mesenchymal chondrosarcoma located in the sacrum of a 23-year-old patient treated with radiotherapy and chemotherapy. A review of the literature on the topic is also reported.

  1. Mesenchymal chondrosarcoma of the orbit: CT and MRI findings

    International Nuclear Information System (INIS)

    Yang, B.T.; Wang, Y.Z.; Wang, X.Y.; Wang, Z.C.

    2012-01-01

    Aim: To describe the computed tomography (CT) and magnetic resonance imaging (MRI) features of orbital mesenchymal chondrosarcomas (MCSs). Materials and methods: Six patients with histology-confirmed MCSs of the orbit were retrospectively reviewed. All six patients underwent CT and MRI. Imaging studies were evaluated for the following: (a) tumour location, (b) configuration, size, and margin, (c) CT attenuation and MRI signal intensity, and (d) secondary manifestations. Additionally, the time–intensity curve (TIC) of dynamic contrast-enhanced (DCE) MRI were analysed in five patients. Results: Two MCSs arose in the right orbit and four in the left orbit. Five MCSs were located in the retrobulbar intraconal space and one in the extraconal space. All the lesions displayed a lobulate configuration and had a well-defined margin. The mean maximum diameter was 25.8 mm (range 15–36 mm). On unenhanced CT, the lesions appeared isodense to grey matter in six patients, with calcifications in five. Two patients showed inhomogeneous, moderate enhancement on enhanced CT. Six MCSs appeared isointense on T1-weighted imaging and heterogeneously isointense on T2-weighted imaging. The lesions showed significantly heterogeneous contrast enhancement. Five patients had DCE MRI and the TICs showed a rapidly enhancing and rapid washout pattern (type III). The following features were also detected: compression of the extra-ocular muscle (six patients, 100%); displacement of the optic nerve (five patients, 83.3%); and encasing globe (three patients, 50%). Conclusions: A well-defined, lobulate orbital mass with calcification on CT and, marked heterogeneous enhancement and type III TIC on MRI are highly suspicious of orbital MCSs.

  2. Femoral mesenchymal chondrosarcoma with secondary aneurysmal bone cysts mimicking a small-cell osteosarcoma

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    Amukotuwa, Shalini A. [St. Vincent' s Hospital, Melbourne (Australia); Choong, Peter F.M.; Powell, Gerard J. [St. Vincent' s Hospital, Department of Orthopaedics, Melbourne (Australia); Smith, Peter J.; Schlicht, Stephen M. [St. Vincent' s Hospital, Department of Medical Imaging, Melbourne (Australia); Thomas, David [Peter MacCallum Cancer Centre, Ian Potter Centre for Cancer Genomics and Predictive Medicine, Melbourne (Australia)

    2006-05-15

    Mesenchymal chondrosarcoma is a rare but aggressive, high-grade malignancy of primitive cartilage-forming mesenchyme that arises most commonly from skeletal sites. Although there are radiological findings suggestive of the diagnosis, imaging features often overlap with those of other skeletal sarcomas. The definitive diagnosis relies on the histological finding of a typical bimorphic appearance, consisting of nests of small, round, poorly differentiated cells and more mature cartilaginous tissue. To highlight this, we present the case of a 21-year-old man who was referred to our institution with a history of right knee pain. Initial imaging and histological evaluation of a core biopsy of the lesion suggested osteosarcoma of the distal right femur; after review, however, the correct diagnosis of mesenchymal chondrosarcoma was made. Adequate tissue sampling and thorough histological evaluation of biopsy specimens is vital for the accurate diagnosis of primary bone malignancies, especially those of chondroid origin. (orig.)

  3. Femoral mesenchymal chondrosarcoma with secondary aneurysmal bone cysts mimicking a small-cell osteosarcoma

    International Nuclear Information System (INIS)

    Amukotuwa, Shalini A.; Choong, Peter F.M.; Powell, Gerard J.; Smith, Peter J.; Schlicht, Stephen M.; Thomas, David

    2006-01-01

    Mesenchymal chondrosarcoma is a rare but aggressive, high-grade malignancy of primitive cartilage-forming mesenchyme that arises most commonly from skeletal sites. Although there are radiological findings suggestive of the diagnosis, imaging features often overlap with those of other skeletal sarcomas. The definitive diagnosis relies on the histological finding of a typical bimorphic appearance, consisting of nests of small, round, poorly differentiated cells and more mature cartilaginous tissue. To highlight this, we present the case of a 21-year-old man who was referred to our institution with a history of right knee pain. Initial imaging and histological evaluation of a core biopsy of the lesion suggested osteosarcoma of the distal right femur; after review, however, the correct diagnosis of mesenchymal chondrosarcoma was made. Adequate tissue sampling and thorough histological evaluation of biopsy specimens is vital for the accurate diagnosis of primary bone malignancies, especially those of chondroid origin. (orig.)

  4. Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFβ as potential targets

    DEFF Research Database (Denmark)

    van Oosterwijk, Jolieke G; Meijer, Danielle; van Ruler, Maayke A J H

    2013-01-01

    The mesenchymal, clear cell, and dedifferentiated chondrosarcoma subtypes are extremely rare, together constituting 10% to 15% of all chondrosarcomas. Their poor prognosis and lack of efficacious treatment emphasizes the need to elucidate the pathways playing a pivotal role in these tumors. We co...

  5. Testicular chondrosarcoma

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    Yalçinkaya Ulviye

    2003-01-01

    Full Text Available A case of primary chondrosarcoma of the testis is reported. A 40-year-old man presented a painless swelling of the right testis that he has been observing for 3 years. Gross examination of the resected specimen showed an encapsulated, gray to tan colored, roughly rounded tumor. Histologically, the tumor revealed a well-differentiated chondrosarcoma.

  6. Myxoid Chondrosarcoma of the Sinonasal Cavity in a Child: a Case Report

    International Nuclear Information System (INIS)

    Kim, Yeo Ju; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Park, Hyun Jin; Kim, Min Sik; Choi, Yeong Jin

    2007-01-01

    Chondrosarcomas are malignant tumors of cartilage that rarely involve the sinonasal region, and myxoid chondrosarcoma is a rare histologic variant of chondrosarcoma that usually occurs in the soft tissue of extremities. Although several case reports and results of small series of chondrosarcomas in the sinonasal region in children are available, myxoid type chondrosarcoma is extremely rare. We recently experienced a case of low grade myxoid chondrosarcoma involving the sinonasal cavity in a 10-year-old boy, and here we report its radiologic-pathologic findings. In this case, chondroid calcification on CT and septal and marginal enhancement on MRI suggested a chondrosarcoma. Whole body PET-CT demonstrated no definite metastatic lesion and a low peak standardized uptake value primary tumor. However, no definite distinguishing imaging features were observed that distinguished low grade myxoid chondrosarcoma from conventional chondrosarcoma. hondrosarcomas are malignant mesenchymal tumors of cartilage, and usually involve the long bone and pelvis. Less than 10% of chondrosarcomas are found in the head and neck region. Chondrosarcomas can occur at any age, but the majority present between the 5th and 7th decades. Therefore, chondrosarcomas of the head and neck in children are rare; only about 13 cases of sinonasal chondrosarcoma in children have been reported. Myxoid chondrosarcoma is a rare histologic variant of chondrosarcoma, and is characterized by abundant chondroid matrix and malignant chondroblastic cells arranged in cords resembling chordoma. Myxoid chondrosarcomas are typically located in the limbs in older patients, and only rarely originate in the head and neck in children. To the best of our knowledge, only one case report of myxoid type chondrosarcoma in the sinonasal region in a child is available. We report a case of myxoid chondrosarcoma involving the sinonasal cavity in a child and describe its computed tomography (CT), magnetic resonance imaging (MRI

  7. Vertebral chondrosarcoma in a blue-fronted parrot (Amazona aestiva

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    Guilherme Reis Blume

    2015-03-01

    Full Text Available Chondrosarcoma is a malignant mesenchymal tumor in which the neoplastic cells produce cartilaginous matrix and is uncommonly described in birds. This report describes the clinical and pathological findings of one case of chondrosarcoma in a blue-fronted parrot (Amazona aestiva. Macroscopically a 3.6x3.5x1.8cm, nodular, ulcerated, and firm mass was identified in the dorsal synsacrum. Microscopically, the mass was composed of a monomorphic proliferation of pleomorphic spindle chondrocytes with abundant cartilaginous matrix, consistent with chondrosarcoma

  8. Chondrosarcoma of the Heart

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    Do Jung Kim

    2015-06-01

    Full Text Available Chondrosarcoma is a rare entity of malignant tumor which arises from cartilaginous tissue, and the literatures on this disease are scarce. The first-line of treatment for cardiac chondrosarcoma is surgery. Due to early local recurrence and distant metastasis, the prognosis is poor even after complete surgical excision. We present a case of chondrosarcoma in the left atrium causing functional mitral stenosis which required urgent surgical intervention, and the successful treatment outcome.

  9. Vertebral chondrosarcoma in a blue-fronted parrot (Amazona aestiva)

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    Blume, Guilherme Reis; Oliveira, Ayisa Rodrigues de; Mattioli, Mariana Portugal; Oliveira, Letícia Batelli de; Reis Junior, Janildo Ludolf; Sant'Ana, Fabiano José Ferreira de

    2015-01-01

    Chondrosarcoma is a malignant mesenchymal tumor in which the neoplastic cells produce cartilaginous matrix and is uncommonly described in birds. This report describes the clinical and pathological findings of one case of chondrosarcoma in a blue-fronted parrot (Amazona aestiva). Macroscopically a 3.6x3.5x1.8cm, nodular, ulcerated, and firm mass was identified in the dorsal synsacrum. Microscopically, the mass was composed of a monomorphic proliferation of pleomorphic spindle chondrocytes with...

  10. Chondrosarcoma of the Thorax

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    Rascoe, Philip A.; Reznik, Scott I.; Smythe, W. Roy

    2011-01-01

    Although a rare entity, chondrosarcoma is the most common malignant tumor of the chest wall. Most patients present with an enlarging, painful anterior chest wall mass arising from the costochondrosternal junction. CT scan with intravenous contrast is the gold standard radiographic study for diagnosis and operative planning. Contrary to previous dictum, resection may be performed in an appropriate surgical candidate based on imaging characteristics or image-guided percutaneous biopsy results; incisional biopsy is rarely required. The keys to successful treatment are early recognition and radical excision with adequate margins, as chondrosarcoma is relatively resistant to radiotherapy and conventional cytotoxic chemotherapy. Overall survival is excellent in most surgical series from experienced centers. Complete excision with widely negative microscopic margins at the initial operation is of the utmost importance, as local recurrence portends systemic metastasis and eventual tumor-related mortality. This paper summarizes data from relevant surgical series and thereupon draws conclusions regarding preoperative, intraoperative, and postoperative management of thoracic chondrosarcoma. PMID:21647360

  11. Clear cell chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, R.; David, R.; Cierney, G. III

    1985-01-01

    The clinical, radiologic, and histopathologic features of three cases of clear cell chondrosarcoma are described. On radiographs, this rather benign-appearing tumor resembles a chondroblastoma when it occurs at the end of a long bone, and may occasionally show a calcified matrix. However, it has distinctive tumor cells with a centrally placed vesicular nucleus surrounded by clear cytoplasm. The lesion has a low-grade malignancy and is amenable to en bloc surgical resection, which results in a much better prognosis than that of conventional chondrosarcoma.

  12. Chondrosarcoma of the Thorax

    Directory of Open Access Journals (Sweden)

    Philip A. Rascoe

    2011-01-01

    Full Text Available Although a rare entity, chondrosarcoma is the most common malignant tumor of the chest wall. Most patients present with an enlarging, painful anterior chest wall mass arising from the costochondrosternal junction. CT scan with intravenous contrast is the gold standard radiographic study for diagnosis and operative planning. Contrary to previous dictum, resection may be performed in an appropriate surgical candidate based on imaging characteristics or image-guided percutaneous biopsy results; incisional biopsy is rarely required. The keys to successful treatment are early recognition and radical excision with adequate margins, as chondrosarcoma is relatively resistant to radiotherapy and conventional cytotoxic chemotherapy. Overall survival is excellent in most surgical series from experienced centers. Complete excision with widely negative microscopic margins at the initial operation is of the utmost importance, as local recurrence portends systemic metastasis and eventual tumor-related mortality. This paper summarizes data from relevant surgical series and thereupon draws conclusions regarding preoperative, intraoperative, and postoperative management of thoracic chondrosarcoma.

  13. Condrossarcoma primário de língua em cão Primary chondrosarcoma in the tongue of a dog

    Directory of Open Access Journals (Sweden)

    A.E. Silva

    2007-04-01

    Full Text Available A 10 year old female Boxer was taken dead to veterinary hospital for a necropsy without any clinical history, showing a growth on the dorsal part of the tongue. Based on the histopathological findings mesenchymal chondrosarcoma was diagnosed. This report describes the first case of chondrosarcoma on the base of the tongue in veterinary medicine.

  14. Managing Epiglottal Chondrosarcoma of a Dog: A case report

    Directory of Open Access Journals (Sweden)

    Ahmed M Shoieb

    2014-08-01

    Full Text Available A primary chondrosarcoma was found in the epiglottis of a 6-year-old, neutered, male Boxer cross-breed dog. Clinically, there was upper respiratory noise, and a 3.2 cm and times; 2.8 cm and times; 2.7 cm, ovoid mass involving the epiglottis was observed. No abnormalities were detected upon radiographic examinations (X-ray of the chest or abdomen. Grossly, the excised mass was hard. On cut section, it displayed a lobular pattern of translucent gray-white color (interpreted as cartilage. Histologically, the epiglottal submucosa contained a non-encapsulated, fairly demarcated multi-nodular neoplasm composed of streams of cells admixed with moderate to abundant amounts of a pale amphophilic to eosinophilic matrix (chondroid. The neoplastic cells stained were immunohistochemically positive for vimentin and S-100 protein, and negative for pancytokeratin. The matrix stained deeply with Alcian Blue (pH 2.5-periodic acid Schiff, which often separated cells into individual lacunae. To the best of our knowledge, this is the first report of extra-skeletal chondrosarcoma primarily arising in the epiglottis of a dog. [J Interdiscipl Histopathol 2014; 2(4.000: 224-227

  15. Extraskeletal effects of vitamin D

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    Maurizio Rossini

    2011-04-01

    Full Text Available In the last years we observed an increasing number of publications about the vitamin D, due to its recognised therapeutic actions and to the widespread hypovitaminosis D. In addition to the well known skeletal benefits, vitamin D can have multiple effects on other tissues.Muscular apparatus: hypovitaminosis D is associated with myopathy, sarcopenia, muscular strength reduction and increased risk of falls. The vitamin D supplementation increases the muscle functionality indexes. Cardiovascular system: low levels of vitamin D are related to increased levels of cardiovascular risk factors, heart failure, stroke, and cardiovascular mortality, while a good vitamin D status is associated with a decreased incidence of cardiovascular diseases. Diabetes and metabolic syndrome: a good vitamin D status is related to a decreased incidence of type 2 diabetes and metabolic syndrome; a vitamin D supplementation in the early childhood reduces (nearly 30% the risk of having type 1 diabetes. Cancer: vitamin D deficit is associated with breast, colorectal cancer and melanoma relapses. Low and high levels of 25-hydroxy-vitamin D (25(OHD are related to a higher neoplastic mortality. Infectious diseases: hypovitaminosis D is associated with higher incidence of upper respiratory tract infections and worse interferon response in chronic hepatitis C. Vitamin D supplementation decreases the risk of having type A influence. Rheumatic diseases: in rheumatoid arthritis low serum levels of vitamin D metabolites are related to a higher disease activity, while a good vitamin D status is associated with a higher probability of remission or response to therapy and a lower degree of disability. Neurologic diseases: associations between vitamin D deficit and risk of multiple sclerosis, depression, cognitive deficits, and Parkinson’s disease have been reported.There is evidence of the extraskeletal effects of vitamin D, but most derive from observational studies: clinical trials

  16. Management of pelvic chondrosarcoma

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    Florin Groșeanu

    2016-11-01

    Full Text Available The partial or complete excision of the hemipelvis with sparing of the lower limb is an option of the treatment of pelvic chondrosarcoma and a therapeutic alternative of the interilio-abdominal disarticulation. The operation has in principle the same indications as the interilio-abdominal disarticulation and offers a good solution for avoiding a mutilating operation. The 149 cases include: 120 biopsies, 29 excisional biopsies, 6 interilioabdominal disarticulations and 14 resections – reconstruction’s, one of with prosthetic reconstruction. The prognostic score was established by assessing: the surgical stage, the site of the tumor, the surgical margins of the tumor, the functional mobility and the postoperative activity. The wide excision of the tumor, a stable reconstruction and an efficient recovery are essential for a successful treatment of pelvic chondrosarcoma. The limb sparing resection-reconstruction represents a highly surgical demanding procedure, followed up by complications in 60% of the cases, so that should be performed only by high skilled surgeons. Hemipelvectomy still remains a well-established life-saving surgery method for patients suffering from vast oncological extensions, where a pelvic resection is not an option.

  17. Chondrosarcoma: With Updates on Molecular Genetics

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    Mi-Jung Kim

    2011-01-01

    Full Text Available Chondrosarcoma (CHS is a malignant cartilage-forming tumor and usually occurs within the medullary canal of long bones and pelvic bones. Based on the morphologic feature alone, a correct diangosis of CHS may be difficult, Therefore, correlation of radiological and clinicopathological features is mandatory in the diagnosis of CHS. The prognosis of CHS is closely related to histologic grading, however, histologic grading may be subjective with high inter-observer variability. In this paper, we present histologic grading system and clinicopathological and radiological findings of conventional CHS. Subtypes of CHSs, such as dedifferentiated, mesenchymal, and clear cell CHSs are also presented. In addition, we introduce updated cytogenetic and molecular genetic findings to expand our understanding of CHS biology. New markers of cell differentiation, proliferation, and cell signaling might offer important therapeutic and prognostic information in near future.

  18. Secondary chondrosarcoma: Malignant transformation of pre ...

    African Journals Online (AJOL)

    Secondary chondrosarcoma: Malignant transformation of pre-existing hereditary and non-hereditary cartilaginous lesions. SCS Vlok, GWW Wagener, D Zaharie. Abstract. Secondary chondrosarcoma is a malignant hyaline cartilage tumour originating from a cartilaginous precursor, either osteochondroma or enchondroma.

  19. New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance.

    Science.gov (United States)

    Monderer, David; Luseau, Alexandrine; Bellec, Amélie; David, Emmanuelle; Ponsolle, Stéphanie; Saiagh, Soraya; Bercegeay, Sylvain; Piloquet, Philippe; Denis, Marc G; Lodé, Laurence; Rédini, Françoise; Biger, Marine; Heymann, Dominique; Heymann, Marie-Françoise; Le Bot, Ronan; Gouin, François; Blanchard, Frédéric

    2013-10-01

    Chondrosarcomas are cartilage-forming, poorly vascularized tumors. They represent the second malignant primary bone tumor of adults after osteosarcoma, but in contrast to osteosarcoma they are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. Few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish new cell lines and animal cancer models from human chondrosarcoma biopsies to study their chemoresistance. Between 2007 and 2012, 10 chondrosarcoma biopsies were collected and used for cell culture and transplantation into nude mice. Only one transplanted biopsy and one injected cell line has engrafted successfully leading to conventional central high-grade chondrosarcoma similar to the original biopsies. In culture, two new stable cell lines were obtained, one from a dedifferentiated and one from a grade III conventional central chondrosarcoma biopsy. Their genetic characterization revealed triploid karyotypes, mutations in IDH1, IDH2, and TP53, deletion in CDKN2A and/or MDM2 amplification. These cell lines expressed mesenchymal membrane markers (CD44, 73, 90, 105) and were able to produce a hyaline cartilaginous matrix when cultured in chondrogenic three-dimensional (3D) pellets. Using a high-throughput quantitative RT-PCR approach, we observed that cell lines cultured in monolayer had lost expression of several genes implicated in cartilage development (COL2A1, COMP, ACAN) but restored their expression in 3D cultures. Chondrosarcoma cells in monolayer were sensitive to several conventional chemotherapeutic agents but became resistant to low doses of mafosfamide or doxorubicin when cultured in 3D pellets, in parallel with an altered nucleic accumulation of the drug. Our results indicate that the cartilaginous matrix produced by chondrosarcoma cells may impair diffusion of several drugs and thus contribute to chemoresistance

  20. Retrobulbar chondrosarcoma in a dog

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    M. Ralić

    2014-04-01

    Full Text Available This paper presents a review of a dog, with a retrobulbar chondrosarcoma, which was admitted for surgery for visible changes in his eye during inspection. Orbital neoplasia in dogs may be primary and secondary. Sixty percent of orbital neoplasia in dogs are primary, ninety percent of which are malignant. Retrobulbar neoplasms are rare and in their early stage represent a diagnostic challenge. Chondrosarcoma of the skull is a slow-progressing malignant disease which occurs locally, aggressive with invasion into the surrounding tissues. Dogs with chondrosarcoma of the skull have life expectancy between 210 and 580 days - in our case it was 180 days - after the first alterations on the eye of the dog occurred.

  1. Chondrosarcoma of the nasal septum

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    Yamamoto, Seiji; Motoori, Ken; Ueda, Takuya; Osaka, Iwao [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8677 (Japan); Takano, Hideyuki [Department of Radiology, Chiba Cancer Center, Chiba (Japan); Nagata, Hiroshi [Department of Otolaryngology, Chiba University Hospital, Chiba (Japan)

    2002-09-01

    The nasal septum is a particularly rare site of origin of chondrosarcoma. Cranial base invasion may be at hand, with such lesions making complete tumor removal difficult. MRI techniques allow precise definition of tumor extent. In the described case, CT and Dynamic MR imaging were performed in a case of chondrosarcoma of the nasal septum. Imaging clearly illustrated size and extent of the mass with central regions of internal calcification. Dynamic MRI was additionally performed, which helped to define the presumed origin of the lesion from the nasal septum. (orig.)

  2. Chondrosarcoma in Hereditary Multiple Exostosis

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... The other bones in the amputated limb were studded with typical benign ... patients); and lastly those with unequivocal clinical, radio- logical and ... CASE REPORTS. Group I. In 15 patients a chondrosarcoma was suspected merely because a large and heavily calcified tumour was discovered on routine ...

  3. Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance

    Directory of Open Access Journals (Sweden)

    Karen A. Boehme

    2018-01-01

    Full Text Available Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC.

  4. Osteosarcomas and chondrosarcomas of the jaws: immunohistochemical correlations.

    Science.gov (United States)

    Regezi, J A; Zarbo, R J; McClatchey, K D; Courtney, R M; Crissman, J D

    1987-09-01

    Clinical, microscopic, and immunohistochemical characteristics of 17 jaw sarcomas are reported. Histologic subtypes included chondroblastic (five), fibroblastic (five), osteoblastic (three), telangiectatic (one), parosteal (two), and chondrosarcoma (one). Reactivity for all antigenic markers in decalcified tissue was judged to be comparable to nondecalcified tissue. All neoplasms were nonreactive for muramidase and leukocyte common antigen. alpha-1 Antichymotrypsin and HLA-DR immunoreactivity was found focally. Positive S-100 staining was found predominantly in chondrocytes. All tumors were positive for vimentin. Cells in focal zones of cartilage were positive for keratin. No distinctive pattern emerged relative to clinical recurrence and histologic subtype or immunotype. Leukocyte common antigen determinations were useful because they distinguished between neoplastic and inflammatory cells. S-100 protein stains helped in the subclassification of chondroblastic osteosarcoma, and vimentin stains confirmed mesenchymal origin. Cross-reactive staining of cartilage with keratin antibodies was regarded as a possible diagnostic pitfall.

  5. Extraskeletal osteosarcoma of the thorax in a goat: case report

    Directory of Open Access Journals (Sweden)

    Becker-Birck Mareike

    2011-09-01

    Full Text Available Abstract Background This report describes the results of clinical, ultrasonographic and computed tomographic examination of a 16-year-old goat with extraskeletal osteosarcoma of the thorax. Case presentation The lead clinical signs were abnormal condition and demeanour, fever, tachycardia, tachypnoea, dyspnoea and dilated jugular veins. Ultrasonographic examination of the thorax revealed a precardial mass, measuring 16.4 by 11.4 by 14.2 cm. Computed tomographic examination showed dorsocaudal displacement of the trachea, heart and lungs to the right. A tentative diagnosis of mediastinal or pleural neoplasia was made, and the goat was euthanased and necropsied. A definitive diagnosis was based on histological examination of the mass. Conclusions To our knowledge, this case report is the first description of extraskeletal osteosarcoma of the thorax in goats and serves to broaden the diagnostic spectrum of thoracic diseases in this species. Extraskeletal osteosarcoma should be part of the differential diagnosis in goats with thoracic tumours.

  6. Primary mesenteric extraskeletal osteosarcoma in the pelvic cavity

    Energy Technology Data Exchange (ETDEWEB)

    Choudur, H.N.; Munk, P.L.; Ryan, A.G.M.J. [Vancouver General Hospital, Department of Radiology, Vancouver, BC (Canada); Nielson, T.O. [Vancouver General Hospital, Department of Pathology, Vancouver, BC (Canada)

    2005-10-01

    A middle-aged man was being investigated for constipation. Abdominal radiographs incidentally revealed a large, densely calcified, rounded mass within the pelvic cavity. A CT scan was performed followed by surgical excision with a differential diagnosis of calcified hematoma and an enlarged calcified lymph nodal mass. Histopathological investigation revealed a primary mesenteric extraskeletal osteosarcoma. To the best of our knowledge, a primary extraskeletal osteosarcoma arising from the mesentery has not been described previously in the English literature. The radiological features and differential diagnosis are discussed. (orig.)

  7. Nasal Osteogenic Chondrosarcoma: A Case Report | Adeniji | West ...

    African Journals Online (AJOL)

    At emergency tracheostomy, examination under anaesthesia, meticulous nasal and nasopharyngeal tumour clearance was done. Histopathological examination of the mass revealed osteogenic chondrosarcoma. CONCLUSION: Though rare, osteogenic chondrosarcoma affects nasal bones. Clinically the tumour mimicks ...

  8. Primary chondrosarcoma of breast - cytology with histopathological correlation: A rare case report with review of literature

    Directory of Open Access Journals (Sweden)

    Sankappa P. Sinhasan

    2014-01-01

    Full Text Available Malignant mesenchymal tumors of the breast other than angiosarcoma are extremely rare and comprise <0.5% of breast tumors. Primary chondrosarcoma of the breast is an extremely rare entity and only 10 cases are reported as single case reports in literature until date. A diagnosis of primary mammary sarcoma can be established only after excluding metaplastic carcinomas and malignant phyllodes by extensive sampling for evidence of in situ or invasive carcinoma. Here, we report a primary chondrosarcoma of breast in a 55-year-old lady diagnosed precisely on fine-needle aspiration cytology and confirmed by histopatholigcal examination after total mastectomy. We emphasize on diagnostic difficulties encountered in cytology smears and discuss differential diagnoses.

  9. Extraskeletal Osteosarcoma: Analysis of Outcome of a Rare Neoplasm

    Directory of Open Access Journals (Sweden)

    Martin D. McCarter

    2000-01-01

    Full Text Available Purpose. Extraskeletal osteosarcoma represents an unusual soft-tissue sarcoma that historically is reported to carry an exceptionally poor prognosis.The objectives of this study were to use a prospectively gathered sarcoma database to test the prevailing clinical bias and more accurately describe the natural history, characterize the prognostic features, estimate survival and evaluate treatment strategies for this unusual sarcoma.

  10. Primary Spinal Chondrosarcoma: Radiologic Findings with Pathologic Correlation

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    Lloret, I.; Server, A. [The Norwegian Radium Hospital, Oslo (Norway). Depts. of Radiology and Pathology; Bjerkehagen, B. [Ullevaal Univ. Hospital, Oslo (Norway). Dept. of Neuroradiology

    2006-02-15

    Purpose: To describe the radiologic appearance of the four types of primary spinal chondrosarcoma (CHS) (conventional intramedullary, juxtacortical, clear cell, and mesenchymal) and to correlate with histopathologic findings. Material and Methods: A retrospective review was carried out of 5 patients with histopathologically confirmed primary spinal CHS; 3 F and 2 M ranging in age between 27 and 66 years (mean 40.2; median 39). Charts, conventional radiographs, computed tomography scans, and magnetic resonance images were reviewed. All the patients underwent surgical excision, followed by postoperative chemotherapy (1 patient) and radiotherapy (3 patients). Follow-up was available for all patients but one. The mean follow-up was 42 months (14-120 months). Histopathological specimens for all patients were available for review. Results: Vertebral column distribution was 3 thoracic (60%), 1 cervical (20%), and 1 lumbar (20%). Neurological deficits were present in 3 (60%) cases. The radiological appearance of the four types of primary spinal CHS varies with specific lesion type. Imaging findings suggest diagnosis of the conventional intramedullary and juxtacortical types. While the clear cell and mesenchymal types show some distinctive features, these do not allow confident radiologic diagnosis. Conclusion: The radiologist must be aware of imaging features of these tumors in order to improve diagnostic accuracy, treatment planning, and prognosis.

  11. Primary Spinal Chondrosarcoma: Radiologic Findings with Pathologic Correlation

    International Nuclear Information System (INIS)

    Lloret, I.; Server, A.; Bjerkehagen, B.

    2006-01-01

    Purpose: To describe the radiologic appearance of the four types of primary spinal chondrosarcoma (CHS) (conventional intramedullary, juxtacortical, clear cell, and mesenchymal) and to correlate with histopathologic findings. Material and Methods: A retrospective review was carried out of 5 patients with histopathologically confirmed primary spinal CHS; 3 F and 2 M ranging in age between 27 and 66 years (mean 40.2; median 39). Charts, conventional radiographs, computed tomography scans, and magnetic resonance images were reviewed. All the patients underwent surgical excision, followed by postoperative chemotherapy (1 patient) and radiotherapy (3 patients). Follow-up was available for all patients but one. The mean follow-up was 42 months (14-120 months). Histopathological specimens for all patients were available for review. Results: Vertebral column distribution was 3 thoracic (60%), 1 cervical (20%), and 1 lumbar (20%). Neurological deficits were present in 3 (60%) cases. The radiological appearance of the four types of primary spinal CHS varies with specific lesion type. Imaging findings suggest diagnosis of the conventional intramedullary and juxtacortical types. While the clear cell and mesenchymal types show some distinctive features, these do not allow confident radiologic diagnosis. Conclusion: The radiologist must be aware of imaging features of these tumors in order to improve diagnostic accuracy, treatment planning, and prognosis

  12. Congenital extraskeletal Ewing's sarcoma of chest wall--a rare case report.

    Science.gov (United States)

    Atla, Bhagyalakshmi; Prasad, B Satya Vara; Sri, K Satya; Vandana, Geeta

    2011-01-01

    Congenital extraskeletal Ewing's sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing's sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing's sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing's sarcoma in neonates are reported in the literature.

  13. An orthotopic mouse model for chondrosarcoma of bone provides an in vivo tool for drug testing

    NARCIS (Netherlands)

    van Oosterwijk, Jolieke G.; Plass, Jacqueline Regina Maria; Meijer, Danielle; Que, Ivo; Karperien, Hermanus Bernardus Johannes; Bovée, Judith V.M.G.

    2015-01-01

    Chondrosarcoma is a malignant cartilaginous tumor of the bone. Recently, mutations in isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) were identified in central chondrosarcomas. As chondrosarcomas are notoriously resistant to conventional treatment modalities, the need for

  14. The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro

    International Nuclear Information System (INIS)

    Lechler, Philipp; Renkawitz, Tobias; Campean, Valentina; Balakrishnan, Sanjeevi; Tingart, Markus; Grifka, Joachim; Schaumburger, Jens

    2011-01-01

    Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro. Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed. Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G 2 /M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment. These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma

  15. Mesenchymal Chondrosarcoma of Posterior Maxilla: Report of a ...

    African Journals Online (AJOL)

    Histologically, the lesion must be differentiated from similar other lesions like hemangiopericytoma, Ewing sarcoma, leukemia/lymphoma, rhabdomyosarcoma, malignant melanoma and small cell osteosarcoma.[8]. The detection of type II collagen in the matrix component of MC was a sensitive marker for the identification of.

  16. Extraskeletal Osteosarcoma of the Thigh: An Autopsy Case Report

    Directory of Open Access Journals (Sweden)

    Akihito Nagano

    2009-01-01

    Full Text Available We report a case of extraskeletal osteosarcoma (ESOS and autopsy findings. A 35-year-old man presented with an ossified tumor in the right thigh and lung metastasis. The lung tumors continued to develop despite multiagent chemotherapy and caused death within 8 months. Autopsy revealed many secondary lesions in the lungs, especially in the left lung. Histopathologically, the primary tumor and one of the secondary tumors showed proliferation of spindle-shaped tumor cells focally forming lace-like osteoid material. Therefore, we made a definite diagnosis of ESOS.

  17. On radiation-induced extraskeletal osteosarcoma: report of a case.

    Science.gov (United States)

    Ascenzi, A; Casagrande, A; Ribotta, G

    1980-04-30

    A case of extraskeletal osteogenic sarcoma arising in the soft tissues of the lower portion of the anterior abdominal wall (subumbelical region) is reported. The tumor developed in an area that had received telecobaltherapy 2 years 8 months previously (total skin dose of 9,000 rads delivered in 45 exposures over two separate periods of 106 and 141 days), after surgical treatment for a Stage I carcinoma of the uterine cervix. The clinical description and histopathology of this unusual neoplasm are presented, and the literature is reviewed.

  18. Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun [Catholic University St. Vincent' s Hospital, Suwon (Korea, Republic of)

    2010-01-15

    Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging.

  19. Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

    International Nuclear Information System (INIS)

    An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun

    2010-01-01

    Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging

  20. Chondrosarcoma of the temporal bone: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Man Soo; Lee, Sang Youl; Chung, Jae Gul; Lee, Deok Hee; Jung, Seung Mun; Ryu, Dae Sik [Kang Nung Hospital, Ulsan Univ. Kangnung (Korea, Republic of)

    2001-07-01

    Chondrosarcoma of the temporal bone is a rare lesion. Clinically it has been confused with chordoma, glomus jugulare tumor and meningioma, among other conditions, and due to its anatomic location, cranial nerve palsy is frequently observed. We report a case involving a 50-year-old woman with chondrosarcoma of the temporal bone.

  1. Unusual metastatic chondrosarcoma detected with a bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Abello, R.; Lomena, F.; Garcia, A.; Herranz, R.; Setoain, J.; Fernandez Sola, J.; Plaza, V.; Sole, M.

    1986-09-01

    A case is presented of a scapular chondrosarcoma which showed intense uptake of Tc-99m MPD in the primary tumour and in the pleural and osseous metastases. Additionally, there was intense visualization of the malignant pleural effusion. The bone scintigraphy correctly diagnosed the extent of the involvement. This finding is unusual because chondrosarcomas in such a disseminated state are relatively rare.

  2. Primary intraocular chondrosarcoma in a dog

    Directory of Open Access Journals (Sweden)

    E. Perlmann

    2013-12-01

    Full Text Available A five-year-old male Cocker Spaniel was presented for evaluation of the right eye due to discomfort, abundant purulent discharge and progressive enlargement of the eyeball. The owner revealed that the right eye has appeared to be inflamed and smaller then the left eye for years. Ophthalmic examination revealed corneal perforation, buphthalmia and conjuctival hyperemia. Enucleating was performed due to signs of endophthalmitis and ocular discomfort. Histopathology revealed a multilobulated proliferation of chondrocytes producing hyaline cartilage with occasional pleomorphism and binucleate cells. A diagnosis of primary intraocular chondrosarcoma was done.

  3. Congenital extraskeletal Ewing′s sarcoma of chest wall - A rare case report

    Directory of Open Access Journals (Sweden)

    Bhagyalakshmi Atla

    2011-01-01

    Full Text Available Congenital extraskeletal Ewing′s sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing′s sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing′s sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing′s sarcoma in neonates are reported in the literature.

  4. Osteosarcoma and chondrosarcoma: radiographic differentiation by means of computed tomography

    International Nuclear Information System (INIS)

    Tossato, Patricia dos Santos; Pereira, Amanda Caceres; Cavalcanti, Marcelo Gusmao Paraiso

    2002-01-01

    The purpose of this paper was to associate and compare the radiographic patterns of osteosarcoma and those of chondrosarcoma by means of computed tomography (CT). Computed tomographs of five cases of osteosarcoma and five cases of chondrosarcoma of the head and neck region were analyzed. The sensitivity of CT was calculated based on the results of histopathological examinations. We concluded that CT can facilitate the establishment of the final diagnosis since it is possible to distinguish the individual characteristics of osteosarcomas and chondrosarcomas in that exam. (author)

  5. Juxtacortical Mandibular Chondrosarcoma during pregnancy: A case report

    OpenAIRE

    Cariati, Paolo; Cabello-Serrano, Almudena; Monsalve-Iglesias, Fernando; Perez-de Perceval-Tara, Miguel; Martinez-Lara, Ildefonso

    2017-01-01

    Chondrosarcoma is one of the most common malignant bone tumors in adults. It use to affect upper arm, pelvis and thigh bone. A wide surgical extirpation represent the gold standard to treat this disorder. In fact, radiotherapy and chemotherapy are no useful. Interestingly, chondrosarcoma is rare in head and neck (HNCS) and extremely uncommon during pregnancy. Thus, there is a lack of evidence about the proper treatment in these cases. A wide surgical extirpation is also considered the most ef...

  6. Conservative cricoid surgery for chondrosarcoma: a case report.

    Science.gov (United States)

    Gaio, Elena; Maggiore, Giandomenico; Canesso, Alessandra; Artico, Riccardo

    2014-02-01

    We present the case of a 39-year-old man who presented with hoarseness and progressively worsening dyspnea. Findings on laryngoscopy and computed tomography strongly suggested the presence of a chondrosarcoma. The patient underwent open surgery for removal of the lesion with wide margins. Reconstruction was carried out with two segments of costal cartilage. Laryngeal chondrosarcomas are rare, malignant, usually well-differentiated neoplasms that should be treated with conservative surgery. Recurrences should be treated more aggressively.

  7. Chondrosarcoma occurring in a patient with polyostotic fibrous dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    De Smet, A.A.; Travers, H.; Neff, J.R.

    1981-12-01

    A 36-year-old white man with polyostotic fibrous dysplasia was found to have a high-grade chondrosarcoma arising from the left ilium. Although a left hemipelvectomy was performed, the patient subsequently developed sacral and pulmonary metastases and succumbed to his disease. This patient represents the first documented example of an unequivocally high-grade chondrosarcoma arising in an area of fibrous dysplasia without prior irradiation.

  8. [Chondrosarcoma of the jaw. A case localized to the mandible].

    Science.gov (United States)

    Oujilal, A; el Alami, M N; Lazrak, A; Jazouli, N; Kzadri, M

    2001-04-01

    Chondrosarcoma is a malignant cartilaginous tumor rarely found in the jaw bone. Tumor progression is slow with strong propensity to local recurrence after surgical removal. The prognosis is poor and depends on the degree of differentiation and the quality of the resection. We report a case of mandibular chondrosarcoma that exhibited particularly massive extension to soft tissue. We discuss the epidemiology, diagnosis, treatment and follow-up of these tumors.

  9. NY-ESO-1 is a sensitive and specific immunohistochemical marker for myxoid and round cell liposarcomas among related mesenchymal myxoid neoplasms.

    Science.gov (United States)

    Hemminger, Jessica A; Iwenofu, O Hans

    2013-09-01

    Myxoid and round cell liposarcomas constitute approximately one-third of all liposarcomas, a relatively common group of fat-derived soft tissue sarcomas. The histomorphology is a continuum between highly differentiated myxoid and poorly differentiated round cell components. The gold standard of diagnosis is dependent on histomorphology and/or identification of t(12;16)(q13;p11) translocation by cytogenetics or demonstration of DDIT3 rearrangements by fluorescence in situ hybridization. There are currently no diagnostic immunohistochemical stains available. The broad range of myxoid neoplasms in the differential diagnosis includes a variety of sarcomas. Given the notable differences in disease biology among myxoid neoplasms, which range from benign to aggressive, an accurate diagnosis is imperative for proper treatment and prognostication. Prompted by our recent study showing frequent expression of the cancer testis antigen NY-ESO-1 in myxoid and round cell liposarcomas, we sought to evaluate the utility of NY-ESO-1 as an immunohistochemical marker for myxoid and round cell liposarcoma among mesenchymal myxoid neoplasms within the differential diagnosis. Formalin-fixed, paraffin-embedded blocks were obtained for the following mesenchymal myxoid neoplasms (n=138): myxoid and round cell liposarcoma (n=38); well-differentiated liposarcoma (n=12); lipoma (n=20; 4 with myxoid change); extra-cardiac soft tissue myxoma (n=39); extraskeletal myxoid chondrosarcoma (n=12); myxofibrosarcoma (n=10: 5 low grade, 2 intermediate grade, 3 high grade); and low-grade fibromyxoid sarcoma (n=7). Utilizing standard immunohistochemistry protocols, full sections were stained with NY-ESO-1 (clone E978), and staining was assessed for intensity (1-2+), percentage of tumor positivity, and location. In all, 36/38 (95%) of the myxoid and round cell liposarcomas demonstrated NY-ESO-1 immunoreactivity. The majority of the positive cases (34/36; 94%) showed strong, homogenous staining (>50% tumor

  10. Laryngeal chondrosarcoma - Ten years of experience

    Directory of Open Access Journals (Sweden)

    José Fernando dos Santos Oliveira

    2014-07-01

    Full Text Available INTRODUCTION: Laryngeal involvement by cartilaginous tumors is rare. However, although accounting for only 1% of laryngeal tumor pathology, they are the most frequently occurring non-epithelial neoplasms. The most probable location is the endolaryngeal surface of the cricoid cartilage. Their symptoms are variable, depending on the size and location, and may include hoarseness, stridor, and dyspnea. Treatment is based on surgical excision. Some centers take into account the degree of differentiation and whether it is a case of relapse when deciding to perform a radical resection. AIM: To evaluate this disease in a sample of the Portuguese population. METHODS: A review of the medical records from 2002 to 2012 by assessment of clinical processes was performed. Data on demographics, clinical treatments, and outcomes were collected. RESULTS: Six patients were included in the study. Five of them underwent total laryngectomy, and in one case, partial excision of the thyroid cartilage was performed. None of the patients had either metastases or tumor-related death. CONCLUSION: Laryngeal chondrosarcomas remain a rare disease of unknown etiology, with slow and insidious symptoms. The treatment is surgical, with favorable prognosis, and metastases rarely occur. The main concern regards their propensity to relapse.

  11. A case of extraskeletal osteosarcoma that developed 28 years after radiation therapy

    International Nuclear Information System (INIS)

    Nishizuka, Satoshi; Tamura, Gen; Maesawa, Chihaya; Shiraishi, Hideo; Satodate, Ryoichi; Yanagisawa, Tohru

    1996-01-01

    We report a case of extraskeletal osteosarcoma that developed in a 63-year-old woman who had received radiation therapy with 60 Coγ-ray 30 Gy each to the left axillary region, spraclavicular pauch and chest wall after left mastectomy for breast cancer. Twenty-eight years after radiation therapy, a tumor appeared in the irradiated field of the chest wall. Histologic examination revealed proliferation of atypical osteoblasts with bone formation; therefore, the tumor was diagnosed as extraskeletal osteosarcoma. Conservative treatment with radiation therapy is an established practice for breast cancer; therefore, long-term follow-up is required for such cases. (author)

  12. Giant Sacral Chondrosarcoma in an Elderly Male : A Case Report

    Directory of Open Access Journals (Sweden)

    HZ Chan

    2014-03-01

    Full Text Available Primary sacral tumours are rare, therefore experience of managing their associated complications are very limited. Effective surgical treatment of pelvic chondrosarcoma remains a major challenge for orthopaedic surgeons, due to the complex anatomic structure of the pelvis, the lack of defined compartment borders, the close vicinity to vital structures, and the risk of jeopardizing pelvic structural stability. We report a rare case of a giant sacral chondrosarcoma (100cm x 80cm in an elderly male who successfully underwent tumour resection with good functional outcome and recovery. Long term follow up is essential in view of the possibility of local tumour recurrence.

  13. Chondrosarcoma of the hyoid bone: computed tomography findings

    International Nuclear Information System (INIS)

    Saez, J.; Gallego, J. a.; Fuster, M. J.

    2001-01-01

    Chondrosarcoma of the hyoid bone is a rare entity, only 10 cases of which have been reported in the literature to date. the case we present involved a 24-year-old man who complained of progressive adynophagia and a mass in anterior neck. Computed tomography revealed a low-attenuation mas attached to the left horn of the hyoid bone. The lesion was excised and was diagnosed as a grade II chondrosarcoma. The patient remains asymptomatic 10 years after the operation. (Author) 11 refs

  14. A chondrosarcoma in the anterior mediastinum mimicking a thymoma

    DEFF Research Database (Denmark)

    Østergaard, Mia L.; Petersen, Rene H; Kalhauge, Anna

    2015-01-01

    A chondrosarcoma in the anterior mediastinum is a rare finding with a relatively good prognosis. We describe a case of a 75-year-old man with a 2-year history of neck discomfort and weight loss. Imaging showed a homogenous tumor with a minor compression on the anterior part of the heart. It had c...... close relation to the ribs, no surrounding fat, and a thymoma was suspected. Biopsy prior to surgery was impossible due to the location of the tumor. Unfortunately, final pathology from the surgical specimen revealed a chondrosarcoma....

  15. The role of imaging in the evaluation of extraskeletal Ewing's sarcoma

    African Journals Online (AJOL)

    Primary bone tumours account for 5% of all adolescent and child cancers. When Ewing's sarcoma arises in soft tissue rather than bone, it is referred to as extraskeletal Ewing's sarcoma (ESS). Computed tomography (CT) scanning and magnetic resonance imaging (MRI) features of Ewing's sarcoma are non-specific, and a ...

  16. CASE SERIES The role of imaging in the evaluation of extraskeletal ...

    African Journals Online (AJOL)

    muscle group and extended to insinuate into the spinal canal, displacing and compressing the thecal sac to the left (Fig. 3). The role of imaging in the evaluation of extraskeletal Ewing's sarcoma. P Barnardt, F Roux. Division of Clinical Oncology, Department of Medical Imaging and Clinical Oncology, Stellenbosch University.

  17. Renal bone disease and extraskeletal calcification during dialysis and after transplantation

    International Nuclear Information System (INIS)

    Graaf, P. de.

    1980-01-01

    The author reports 10 studies concerning the diagnosis of renal osteodystrophy and extraskeletal calcification in patients on maintenance hemodialysis as well as some aspects of persistent hyperparathyroidism after renal transplantation. The majority of the studies focus on the value of bone scintigraphy with Tc-99m HEDP in the diagnosis of these disorders. (Auth.)

  18. Hyoid bone chondrosarcoma with cervical nodal metastasis: A case ...

    African Journals Online (AJOL)

    Hisham Mostafa Abdel-Fattah

    2015-11-18

    Nov 18, 2015 ... CT scan features include enchondroma and osteoblastoma, but they are very rare in the head and neck.13. MRI gives a better idea regarding the surrounding soft tis- sue involvement. Chondrosarcoma appears heterogeneously hypointense in T1 weighted images, with strong peripheral enhancement.

  19. Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Thomas Kalinski

    Full Text Available Interleukin (IL-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

  20. Chondrosarcoma in a wild great white heron from southern Florida.

    Science.gov (United States)

    Spalding, M G; Woodard, J C

    1992-01-01

    A typical chondrosarcoma is reported from the nictitating membrane of a great white heron (Ardea herodius occidentalis). This is the first report of a neoplasm in a free flying ciconiiform, and was the only one found in a survey of 957 carcasses from Florida.

  1. Retrobulbar chondrosarcoma in a dog | Ralić | Open Veterinary ...

    African Journals Online (AJOL)

    This paper presents a review of a dog, with a retrobulbar chondrosarcoma, which was admitted for surgery for visible changes in his eye during inspection. Orbital neoplasia in dogs may be primary and secondary. Sixty percent of orbital neoplasia in dogs are primary, ninety percent of which are malignant. Retrobulbar ...

  2. Tissue microarrays analysis in chondrosarcomas: light microscopy, immunohistochemistry and xenograft study.

    Science.gov (United States)

    Machado, Isidro; Giner, Francisco; Mayordomo, Empar; Carda, Carmen; Navarro, Samuel; Llombart-Bosch, Antonio

    2008-07-15

    Chondrosarcoma (Chs) is the third most frequent primary malignant tumour of bone and can be primary or secondary, the latter results mainly from the malignant transformation of a benign pre-existing tumour. All the cases diagnosed as Chs (primary tumours, recurrences and/or metastasis and xenotransplanted Chs) from the files of our Department were collected. Only cases with paraffin blocks available were selected (Total 32 cases). Six Tissue Microarrays (TMAs) were performed and all the cases and biopsies were distributed into the following groups: a) only paraffin block available from primary and/or metastatic tumours (3 TMAs), b) paraffin block available from primary and/or metastatic tumours as well as from the corresponding Nude mice xenotransplant (2 TMAs), c) only paraffin block available from xenotransplanted Chs (1 TMA). A reclassification of all the cases was performed; in addition, conventional hematoxylin-eosin as well as immunohistochemistry staining (S100, SOX-9, Ki-67, BCL-2, p53, p16, CK, CD99, Survivin and Caveolin) was analyzed in all the TMA. The distribution of the cases according to the histopathological pattern and the location of tumours were as follows: fourteen Grade I Chs (all primaries), two primary Grade II Chs, ten Grade III Chs (all primaries), five dedifferentiated Chs (four primaries and one primary with metastasis), and two Chs from cell cultures (Ch grade III). One recurrent extraskeletal myxoid Chs was included as a control in the TMA. Although there was heterogeneity in immunohistochemistry results of the different material analyzed, S100, SOX-9, Caveolin and Survivin were more expressed. The number of passages in xenotransplants fluctuated between 1 and 13. Curiously, in Grade I Chs, these implanted tumours hardly grew, and the number of passages did not exceed one. The study of Chs by means of TMA techniques is very important because it will improve the assessment of different antibodies applied in the immunohistochemical assays

  3. Chondrosarcoma in the mental foramen region of the mandible: A case report.

    Science.gov (United States)

    Liu, Hongwei; Chen, Xiuhong; Wan, Teng; Li, Ren

    2016-09-01

    Chondrosarcoma is a malignant tumor that is characterized by the formation of cartilage by tumor cells. The tumor is commonly observed in regions where cartilage is already present. In total, 5-12% of chondrosarcomas occur in the head and neck region. However, the occurrence of chondrosarcoma in the mental foramen region is extremely rare. The aim of the present study was to report a case of chondrosarcoma in the mental foramen region. An 18-year-old man presented with a 3-month history of a painless mass over the labial aspect of the right mandible, which was associated with the patient feeling unwell and the loosening of the lower anterior teeth. The patient underwent segmental mandibulectomy and the final pathological diagnosis was chondrosarcoma. Following mandibulectomy, the patient continued to receive routine follow-up. In addition, the present study reviewed the literature concerning chondrosarcomas in the head and neck region.

  4. What are the differentiating clinical and MRI-features of enchondromas from low-grade chondrosarcomas?

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan [Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); University Hospital Birmingham, Department of Radiology, Birmingham (United Kingdom); Parry, M. [Royal Orthopaedic Hospital, Department of Orthopaedic Oncology, Birmingham (United Kingdom); Vaiyapuri, S. [Royal Orthopaedic Hospital, Department of Musculoskeletal Pathology, Birmingham (United Kingdom); Davies, A.M. [Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom)

    2018-01-15

    To evaluate the role of clinical assessment, conventional and dynamic contrast-enhanced MRI in differentiating enchondromas from chondrosarcomas of long bone. The following clinical and MRI findings were assessed: age, gender, pain, pain attributable to lesion, tumour location, tumour length, presence, depth of endosteal scalloping, bone marrow oedema, soft tissue oedema, cortical destruction, periosteal reaction, bone expansion, macroscopic fat, calcification, soft tissue mass, haemorrhage, dynamic contrast-enhanced MRI. Clinical and MRI findings were compared with histopathological grading. Sixty patients with central chondroid tumours were included (27 enchondromas, 10 cartilaginous lesions of unknown malignant potential, 15 grade 1 chondrosarcomas, 8 high-grade chondrosarcomas). Pain attributed to lesion, tumour length, endosteal scalloping > 2/3, cortical destruction, bone expansion and soft tissue mass were differentiating features between enchondromas and grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI could not differentiate enchondromas from grade 1 chondrosarcomas. Previously reported imaging signs of chondrosarcomas are useful in the diagnosis of grade 1 lesions but have lower sensitivity than in higher grade lesions. Deep endosteal scalloping is the most sensitive imaging sign of grade 1 chondrosarcomas. Pain due to the lesion is an important clinical sign of grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI is not useful in differentiating enchondromas from grade 1 chondrosarcomas. (orig.)

  5. Laryngeal Chondrosarcoma: A rare cause of critical upper airway obstruction.

    LENUS (Irish Health Repository)

    Tuite, K

    2018-01-01

    Laryngeal cancers are rare, encompassing around one percent of all cancers. Suspicion should be raised if a patient presents with classical signs and symptoms; i.e. dysphonia, inspiratory stridor, dysphagia, odynophagia, neck mass, or persistent cough. Laryngeal chondrosarcoma is a rare form of laryngeal cancer, the diagnosis of which can be difficult. The case in question describes an unusual presentation of one such case, and its subsequent investigation, management and outcome.

  6. Extraskeletal aneurysmal bone cyst: Report of a case and review of the literature.

    Science.gov (United States)

    Lopez, Liurka V; Rodriguez, Michael G; Siegal, Gene P; Wei, Shi

    2017-11-01

    Aneurysmal bone cyst (ABC) is an expansile cystic lesion that may affect any bone of the skeleton. Although exceedingly rare, lesions with histomorphologic characteristics of an ABC have reportedly originated within soft tissue. Extraskeletal ABC may mimic a variety of benign and malignant lesions and can be confused with other more common or rare giant cell-rich tumors of soft tissue, especially myositis ossificans. Clinical, radiological and histologic correlation is crucial in reaching the correct diagnosis. Cytogenetic and/or molecular genetic analysis is a useful adjunct in diagnosing these exquisitely rare lesions. Here we report a case of an ABC arising in an extraskeletal site and provide a comprehensive review of literature on this rare entity. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Canine spirocercosis-associated extraskeletal osteosarcoma with central nervous system metastasis

    Directory of Open Access Journals (Sweden)

    Paolo Pazzi

    2013-04-01

    Full Text Available A five-year-old male Boerboel presented for examination, collapsed for an unknown period of time. On clinical examination, multifocal subcutaneous masses and enlarged prescapular lymph nodes as well as neurological deficits that suggested a multifocal neurological syndrome were found. Fine needle aspirates of the prescapular lymph nodes revealed cells suggestive of osteosarcoma. Radiographs showed foci of mineralisation within the soft tissue masses as well as diffuse pulmonary metastasis and a caudodorsal mediastinal mass believed to be a Spirocerca lupi nodule. Computed tomography imaging, necropsy and histopathology confirmed S. lupi oesophageal neoplastic transformation (extraskeletal osteosarcoma, believed to be the primary lesion, and the majority of secondary metastasis to the brain, spine, heart, multiple muscular groups and abdominal organs. This is the first known report of extraskeletal osteosarcoma metastasis to the brain and spinal cord in a dog.

  8. ADAMTS13 expression in human chondrosarcoma cells induced by insulin

    Directory of Open Access Journals (Sweden)

    Rıdvan Fırat

    2014-06-01

    Full Text Available Objectives: A Disintegrin-like Metalloproteinase with Thrombospondin Motifs (ADAMTS proteins is a proteinase enzyme group that primarily located in the extracellular matrix (ECM. Insulin has been known to stimulate proteoglycan biosynthesis in chondrosarcoma chondrocytes and thereby the levels of ADAMTS proteins. The aim of this study is to evaluate the time-dependent effects of insulin on the ADAMTS13 expression in OUMS-27 human chondrosarcoma cell line to test the hypothesis that insulin diminishes ADAMTS13 expression because of its anabolic effects. Methods: To test this hypothesis OUMS-27 cells were cultured in Dulbecco’s modified Eagle’ medium (DMEM containing 10μg/mL insulin. The medium containing insulin was changed every other day up to 11th day. Cells were harvested at 1, 3, 7, and 11th days and protein and RNA isolations were performed at the proper times. The levels of RNA expression of ADAMTS13 was quantified by qRT-PCR using appropriate primers while protein levels was detected by Western blot technique using anti-ADAMTS13 antibody. Results: Although there was a decrease in both RNA and protein levels in insulin-applied groups compared to the control cells, it was not statistically significant. Conclusion: Under the light of our findings, it is suggested that insulin does not participate in regulation of ADAMTS13 in OUMS-27 chondrosarcoma cells. J Clin Exp Invest 2014; 5 (2: 226-232

  9. Laryngeal chondrosarcoma diagnosed by core-needle biopsy.

    Science.gov (United States)

    Miyamaru, Satoru; Haba, Koichi

    2014-01-01

    We report a case of chondrosarcoma of the larynx, diagnosed by a percutaneous core-needle biopsy (CNB). Cartilaginous tumors of the larynx are usually diagnosed by biopsy with direct laryngomicroscopy under general anesthesia. However, patients find it difficult to undergo a biopsy under general anesthesia, for physical, economic, and social reasons. Instead, we can readily detect and sample tumors of the larynx using ultrasound under local anesthesia with reduced stress. Concerning needle-puncture biopsies, including fine-needle aspiration cytology (FNAC) and CNB, some studies have reported needle track dissemination, a possible complication in patients with malignant tumors. Thus, in the head and neck region, we generally use FNAC for biopsies, not CNB. However, it can be difficult to diagnose bone tumors by cytology alone. Regarding primary bone tumors, only one study has reported needle track dissemination by CNB, in osteosarcoma of the femur. Additionally, this complication has not been reported before with chondrosarcoma anywhere in the body. To our knowledge, this is the first report concerning chondrosarcoma of the larynx diagnosed by percutaneous CNB. We recommend CNB as a useful and safe diagnostic technique for primary bone tumors in the head and neck region. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Primary Extraskeletal Ewing Sarcoma Originating From Chest Wall in a Child

    OpenAIRE

    Avcu, Serhat; Akdeniz, Hüseyin; Bora, Aydın; Arslan, Harun; Ünal, Özkan

    2015-01-01

    We report the ultrasonography (US) and computed tomography (CT) findings of a rare case of extraskeletal Ewing sarcoma involving the left chest wall with a diameter of 4cm in a 5 years old girl. The lesion was heterogenously hypoechoic on sonography with a lobulated smooth contour. On CT, the lesion had central necrotic areas and was enhancing heterogeneously. With these US and CT findings surgical excision of the tumor was performed. Histopathologically the mass was evaluated as round cell m...

  11. Recurrent primary lumbar vertebra chondrosarcoma: Marginal resection and Iodine-125 seed therapy

    Directory of Open Access Journals (Sweden)

    Chunpeng Ren

    2014-01-01

    Full Text Available Chondrosarcomas are uncommon in the spinal column. En bloc excisions with wide margins are of critical importance but not always feasible in spine. We report the outcome in a case of recurrent lumbar vertebral chondrosarcoma treated with marginal resection and iodine-125 seeds placed in the resected tumor bed.

  12. Hedgehog pathway inhibition in chondrosarcoma using the smoothened inhibitor IPI-926 directly inhibits sarcoma cell growth.

    Science.gov (United States)

    Campbell, Veronica T; Nadesan, Puviindran; Ali, S Amanda; Wang, Chang Ye Yale; Whetstone, Heather; Poon, Raymond; Wei, Qingxia; Keilty, John; Proctor, Jennifer; Wang, Lauren W; Apte, Suneel S; McGovern, Karen; Alman, Benjamin A; Wunder, Jay S

    2014-05-01

    Hedgehog (Hh) pathway inhibition in cancer has been evaluated in both the ligand-independent and ligand-dependent settings, where Hh signaling occurs either directly within the cancer cells or within the nonmalignant cells of the tumor microenvironment. Chondrosarcoma is a malignant tumor of cartilage in which there is ligand-dependent activation of Hh signaling. IPI-926 is a potent, orally delivered small molecule that inhibits Hh pathway signaling by binding to Smoothened (SMO). Here, the impact of Hh pathway inhibition on primary chondrosarcoma xenografts was assessed. Mice bearing primary human chondrosarcoma xenografts were treated with IPI-926. The expression levels of known Hh pathway genes, in both the tumor and stroma, and endpoint tumor volumes were measured. Gene expression profiling of tumors from IPI-926-treated mice was conducted to identify potential novel Hh target genes. Hh target genes were studied to determine their contribution to the chondrosarcoma neoplastic phenotype. IPI-926 administration results in downmodulation of the Hh pathway in primary chondrosarcoma xenografts, as demonstrated by evaluation of the Hh target genes GLI1 and PTCH1, as well as inhibition of tumor growth. Chondrosarcomas exhibited autocrine and paracrine Hh signaling, and both were affected by IPI-926. Decreased tumor growth is accompanied by histopathologic changes, including calcification and loss of tumor cells. Gene profiling studies identified genes differentially expressed in chondrosarcomas following IPI-926 treatment, one of which, ADAMTSL1, regulates chondrosarcoma cell proliferation. These studies provide further insight into the role of the Hh pathway in chondrosarcoma and provide a scientific rationale for targeting the Hh pathway in chondrosarcoma.

  13. Desmoid tumor of bone with enchondromatous nodules, mistaken for chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Won-Jong [Musculoskeletal Oncology Study Group, Catholic University of Korea (Korea); Department of Orthopaedic Surgery, Uijongbu St. Mary' s Hospital, 65-1 Geumohdong, Uijongbu, Gyunggido, 480-130 (Korea); Kang, Yong-Koo; Lee, An-Hee [Musculoskeletal Oncology Study Group, Catholic University of Korea (Korea); Mirra, Joseph M. [Orthpaedic Oncology, Orthopaedic Hospital, Los Angeles, CA (United States)

    2003-04-01

    Desmoid tumor of bone, also termed desmoplastic fibroma or aggressive fibromatosis, is a rare, locally aggressive fibroblastic tumor. We present a 16-year-old male with a huge desmoid tumor involving the iliac wing. It was associated with enchondromatous nodules mimicking malignancy. The tumor in this patient was mistaken for chondrosarcoma and hemipelvectomy was performed. To our knowledge, such a case has not previously been documented fully in the English literature. The radiographic and pathologic findings and a possible mechanism of enchondromatous nodule formation in fibrous bone tumors are discussed. (orig.)

  14. Laryngeal Chondrosarcoma as a Rare Cause of Subglottic Stenosis

    Directory of Open Access Journals (Sweden)

    Kerem Kökoğlu

    2014-01-01

    Full Text Available Laryngeal chondrosarcoma (CS is a very rare entity. It is usually seen in 50–80-year olds. It is developed from cricoid cartilage largely. Patients have laryngeal CS complaint of respiratuvar distress, dysphonia, and dysphagia generally. A submucous mass is usually seen in physical examination with an intact mucosa. Distant metastasis is rare in CSs. Main treatment is surgical excision. An 82-year-old patient who has respiratuvar distress is presented in this paper and laryngeal CS is reviewed in the light of the literature.

  15. High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123 for Extraskeletal Ewing's Sarcoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Tomoya Sakabe

    2011-01-01

    Full Text Available Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123 contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment.

  16. Chondrosarcoma of the Proximal Phalanx of the Fourth Digit: A Rare Location

    Directory of Open Access Journals (Sweden)

    Thivi Vasilakaki

    2012-10-01

    Full Text Available Introduction: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. The small bones of the hands and feet are rarely involved by primary chondrosarcoma. Proximal phalanges are the most common sites in the hands, but the fourth digit is the least common site. Case Presentation: We report a case of a 76-year-old Greek female who presented to our hospital with a painful swollen mass measuring 4.5 × 2.6 cm on the fourth digit of the left hand. The radiograph showed a destructive, permeative lytic tumor of the proximal phalanx with extension into soft tissue. The patient underwent curettage, and the microscopic examination of the specimen revealed grade 2 chondrosarcoma. Conclusion: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. Primary chondrosarcoma is the third most common malignancy of bone after myeloma and osteosarcoma, but the small bones of the hands and feet are very rarely involved by chondrosarcoma (1% of all chondrosarcoma. However, in these cases differentiation between a benign lesion and chondrosarcoma may be difficult. Occasionally chondrosarcoma of the hands and feet is associated with multiple recurrences or distal metastasis.

  17. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Su, Chen-Ming [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Wang, Shih-Wei [Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China); Lee, Tzong-Huei [Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China); Tzeng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China); Hsiao, Che-Jen [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Liu, Shih-Chia [Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2013-10-15

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

  18. Extraskeletal ewing's sarcoma family of tumors in adults. Prognostic factors and clinical outcome

    International Nuclear Information System (INIS)

    Tural, D.; Molinas Mandel, N.; Dervisoglu, S.

    2012-01-01

    The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewing's sarcoma. Data of patients with extraskeletal Ewing's sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewing's sarcoma. (author)

  19. The impact of vitamin D in pregnancy on extraskeletal health in children

    DEFF Research Database (Denmark)

    Christesen, Henrik T; Elvander, Claes; Lamont, Ronald F

    2012-01-01

    The impact of maternal vitamin D status in pregnancy on the extraskeletal health of the offspring has become a "hot topic" with a potential for cost-beneficial prevention. The objective of this study was to systematically review the level I and II evidence. PubMed, Embase and Cochrane databases...... were searched using the MeSH terms "vitamin D" AND "pregnancy" until 1 January 2012. The search was limited to randomized controlled trials (evidence level I) and observational studies (evidence level II) in humans and in the English language. Papers reporting on vitamin D supplementation...

  20. Is bone scintigraphy necessary in the initial surgical staging of chondrosarcoma of bone?

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan; James, Steven L.; Davies, Mark A. [Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); Grimer, Robert J. [Royal Orthopaedic Hospital, Department of Orthopaedic Oncology, Birmingham (United Kingdom)

    2012-04-15

    To assess the value of whole-body bone scintigraphy in the initial surgical staging of chondrosarcoma of bone. A retrospective review was conducted of the bone scintigraphy reports of a large series of patients with peripheral or central chondrosarcoma of bone treated in a specialist orthopaedic oncology unit over a 13-year period. Abnormal findings were correlated against other imaging, histological grade and the impact on surgical staging. A total of 195 chondrosarcomas were identified in 188 patients. In 120 (63.8%) patients the reports of bone scintigraphy noted increased activity at the site of one or more chondrosarcomas. In one patient the tumour was outside the field-of-view of the scan, and in the remaining 67 (35.6%) cases, there was increased activity at the site of the chondrosarcoma and further abnormal activity in other areas of the skeleton. Causes of these additional areas of activity included degenerative joint disease, Paget's disease and in one case a previously undiagnosed melanoma metastasis. No cases of skeletal metastases from the chondrosarcoma were found in this series. Multifocal chondrosarcomas were identified in three cases. In two it was considered that all the tumours would have been adequately revealed on the initial MR imaging staging studies. In only the third multifocal case was an unsuspected, further presumed low-grade, central chondrosarcoma identified in the opposite asymptomatic femur. Although this case revealed an unexpected finding the impact on surgical staging was limited as it was decided to employ a watch-and-wait policy for this tumour. There is little role for the routine use of whole-body bone scintigraphy in the initial surgical staging in patients with chondrosarcoma of bone irrespective of the histological grade. (orig.)

  1. Radiographic differentiation of enchondroma from low-grade chondrosarcoma in the fibula

    International Nuclear Information System (INIS)

    Kendell, Scott D.; Collins, Mark S.; Adkins, Mark C.; Sundaram, Murali; Unni, Krishnan K.

    2004-01-01

    To evaluate demographic and radiographic features that may differentiate between enchondroma and low-grade chondrosarcoma of the fibula. The radiographs of ninety-three histologically-confirmed cartilaginous tumors of the fibula were retrospectively reviewed along with demographic information as to patient age and gender. Fifty-four enchondromas and thirty-nine low-grade chondrosarcomas were included in the study. Multiple previously-established radiographic features distinguishing enchondroma from chondrosarcoma were evaluated in each fibular tumor in a consensus manner by two experienced, board-certified and fellowship-trained musculoskeletal radiologists. Five radiographic features were shown to statistically favor chondrosarcoma over enchondroma in the fibula. These were soft-tissue mass (p<0.0001), periosteal reaction (p=0.008), cortical disruption in the juxta-articular fibula (p=0.0133), cortical thickening (p=0.032), and tumor size greater than 4 cm (p=0.0046). No statistically-significant demographic differences were found between patients with enchondroma and chondrosarcoma of the fibula. When two or more of the identified features of malignancy are identified in the same patient, chondrosarcoma is 2.4 times more likely than in those patients exhibiting none of the features of malignancy. Soft-tissue mass, periosteal reaction, cortical disruption in the juxta-articular fibula, cortical thickening, and tumor size greater than 4 cm indicate chondrosarcoma over enchondroma of the fibula. Radiographs demonstrating more than one of the identified malignant features are more likely to be due to chondrosarcoma than radiographs demonstrating none or only one of the identified features. No unique malignant features of chondrosarcoma in the fibula were observed when compared to previous descriptions of these tumors in the long and short tubular bones of the appendicular skeleton. (orig.)

  2. Recurrence of Pelvic Chondrosarcoma through Fascial Defect into Abdominal Cavity

    Directory of Open Access Journals (Sweden)

    Kemal Gökkuş

    2014-01-01

    Full Text Available Our patient was a 76-year-old female who has been operated on 2 times in 8 years for pelvic chondrosarcoma. The patient came to our clinic with a large mass in left iliac region which extended into the paravertebral area. Physical examination and preoperative imagining studies revealed a mass at the left iliac area that infiltrated sciatic notch and extended from posterior iliac region towards the anterior side of iliac bone through the sciatic notch and an incisional hernia including descending colon. The mass was also penetrating the abdominal cavity through the hernia. Surgical intervention was planned. Since the tumor infiltrated the sciatic nerve, hemipelvectomy was indicated. Patient refused hemipelvectomy. Therefore, palliative debulking surgery was considered. We treated the case with marginal excision and abdominal wall reconstruction employing prolene and vicryl suture materials in order to prevent a postoperative visceral herniation and local invasion. At the latest follow-up appointment in 2 years, the patient still had no signs of tumor recurrence. This case showed us that an incisional hernia can serve as a pathway for the recurrence invasion of the chondrosarcoma.

  3. McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

    Directory of Open Access Journals (Sweden)

    Collins Michael T

    2012-05-01

    Full Text Available Abstract Fibrous dysplasia (FD is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS. The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues. The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.

  4. Dedifferentiated chondrosarcoma in patients with multiple osteochondromatosis: report of a case and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kilpatrick, S.E. [Department of Pathology, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States); Pike, E.J. [Department of Radiology, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States); Ward, W.G. [Department of Orthopaedics, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States); Pope, T.L. [Department of Radiology, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States)

    1997-06-01

    Multiple osteochondromatosis (MOS) is a familial disorder of autosomal dominant transmission characterized by the development of multiple exostoses and often derangements of epiphyseal cartilage, sometimes resulting in long bone growth retardation. Patients with the disorder appear to be at increased risk for developing secondary chondrosarcomas. Rarely, dedifferentiated chondrosarcomas may also occur. We report a single case of a 27-year-old man with multiple osteochondromatosis who developed a fatal dedifferentiated chondrosarcoma. Radiographically, the neoplasm arose from the pelvis completely destroying the left pubic ramus. Subsequently, the patient underwent preoperative chemotherapy followed by a left external hemipelvectomy. On pathologic examination, the tumor was characterized by high-grade pleomorphic sarcoma sharply juxtaposed to a low-grade chondrosarcoma. The patient ultimately died of widespread metastatic sarcoma. (orig.). With 7 figs.

  5. Chondroblastoma and clear cell chondrosarcoma: radiological and MRI characteristics with histopathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kaim, Achim H.; Huegli, Rolf [Institute of Diagnostic Radiology, University Hospital Basle (Switzerland); Bonel, Harald M. [Institute of Clinical Radiology, University Hospital, Munich-Grosshadern (Germany); Jundt, Gernot [Institute of Pathology, University Hospital Basle (Switzerland)

    2002-02-01

    Objective: To analyze and compare the radiological and magnetic resonance imaging (MRI) appearances of chondroblastoma and clear cell chondrosarcoma with histopathological correlation. Design and patients: Twelve patients with histologically proven chondroblastoma and of another four patients with clear cell chondrosarcoma were investigated by radiographs and MRI (T1-, T2-weighted sequences, intravenous gadolinium application). Additionally, the clinical and radiologic data of seven cases of clear cell chondrosarcoma without available MRI were considered. The localization, calcification of tumor matrix, periosteal reaction, cortical bone and patterns of bone destruction were analyzed according to the Lodwick radiological grading system (LRGS). The signal intensity on T1- and T2-weighted sequences, characteristics of contrast enhancement, associated bone marrow edema, soft tissue reaction and joint involvement were evaluated. Histopathological specimens were available in all cases. Results: The age of patients with chondroblastoma (range 15-59 years, mean 22.3 years) was lower than that of those with clear cell chondrosarcoma (range 19-61 years, mean 36.6 years), and the lesions were smaller in the chondroblastoma group (range 1-4 cm, mean 2.3 cm) than in patients with clear cell chondrosarcoma (range 3-7.5 cm, mean 5.2 cm). The chondroblastomas were more confined to the epiphysis (10/12) than the clear cell chondrosarcomas. All chondroblastomas and clear cell chondrosarcomas except one were classified as grade 1A or 1B according to the LRGS; one clear cell chondrosarcoma was judged as grade 2. Signal intensity of the tumors on MRI was very heterogeneous in both groups. High signal intensity on T2-weighted MR images in chondroblastoma mostly corresponded to areas with aneurysmal bone cyst components and in clear cell chondrosarcoma to islands of hyaline cartilage. Contrast enhancement occurred in all tumors and tended to be more intense with clear cell

  6. NY-ESO-1 (CTAG1B) expression in mesenchymal tumors.

    Science.gov (United States)

    Endo, Makoto; de Graaff, Marieke A; Ingram, Davis R; Lim, Simin; Lev, Dina C; Briaire-de Bruijn, Inge H; Somaiah, Neeta; Bovée, Judith V M G; Lazar, Alexander J; Nielsen, Torsten O

    2015-04-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1, CTAG1B) is a cancer-testis antigen and currently a focus of several targeted immunotherapeutic strategies. We performed a large-scale immunohistochemical expression study of NY-ESO-1 using tissue microarrays of mesenchymal tumors from three institutions in an international collaboration. A total of 1132 intermediate and malignant and 175 benign mesenchymal lesions were enrolled in this study. Immunohistochemical staining was performed on tissue microarrays using a monoclonal antibody for NY-ESO-1. Among mesenchymal tumors, myxoid liposarcomas showed the highest positivity for NY-ESO-1 (88%), followed by synovial sarcomas (49%), myxofibrosarcomas (35%), and conventional chondrosarcomas (28%). Positivity of NY-ESO-1 in the remaining mesenchymal tumors was consistently low, and no immunoreactivity was observed in benign mesenchymal lesions. On the basis of these findings, nearly 90% of myxoid liposarcomas, as well as a significant proportion of synovial sarcomas, myxofibrosarcomas, and conventional chondrosarcomas are good candidates for immunotherapy targeting NY-ESO-1.

  7. Myxoid Chondrosarcoma of Maxilla in a Pediatric Patient: A Rare Case Report

    OpenAIRE

    Nimonkar, Pranali; Bhola, Nitin; Jadhav, Anendd; Jain, Anuj; Borle, Rajiv; Ranka, Rajul; Chaudhary, Minal

    2016-01-01

    Myxoid variant of chondrosarcoma is an uncommon potentially lethal malignant tumor which is even rare in pediatric age group. In the present paper, we report one such case of intermediate grade myxoid chondrosarcoma of left side of maxilla in a 12-year-old girl. The present case had a firm, painless, and lobulated growth in premolar-molar region which was associated with bicortical expansion. Maxillofacial imaging showed ill-defined radiolucency with displaced maxillary molars. Osteolytic cha...

  8. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    Directory of Open Access Journals (Sweden)

    Hamm Christopher A

    2010-09-01

    Full Text Available Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that

  9. Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis.

    Science.gov (United States)

    Zhang, Huan-Tian; Yang, Jie; Liang, Gui-Hong; Gao, Xue-Juan; Sang, Yuan; Gui, Tao; Liang, Zu-Jian; Tam, Man-Seng; Zha, Zhen-Gang

    2017-12-01

    Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of β-catenin were not altered upon the treatment of Andro, suggesting that β-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    International Nuclear Information System (INIS)

    Hamm, Christopher A; Wang, Deli; Malchenko, Sergey; Fatima Bonaldo, Maria de; Casavant, Thomas L; Hendrix, Mary JC; Soares, Marcelo B; Stevens, Jeff W; Xie, Hehuang; Vanin, Elio F; Morcuende, Jose A; Abdulkawy, Hakeem; Seftor, Elisabeth A; Sredni, Simone T; Bischof, Jared M

    2010-01-01

    Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis

  11. Enchondroma vs. chondrosarcoma: A simple, easy-to-use, new magnetic resonance sign

    Energy Technology Data Exchange (ETDEWEB)

    Vanel, Daniel, E-mail: daniel.vanel@ior.it [Department of Research, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Kreshak, Jennifer [Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Larousserie, Frédérique [Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Alberghini, Marco; Mirra, Joe [Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); De Paolis, Massimiliano [Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Picci, Piero [Department of Research, Istituto Ortopedico Rizzoli, Bologna (Italy)

    2013-12-01

    Introduction: There is no clear radiologic or pathologic agreement on the differences between enchondroma and conventional chondrosarcoma, which has huge therapeutic consequences. Microscopically, an enchondroma is composed of “islands of intramedullary hyaline cartilage surrounded by marrow fat”, and a chondrosarcoma a “diffuse cartilaginous replacement (invasion) of the marrow which leads to complete ‘trapping’ of host lamellar bone trabeculae.” The marrow around islands of cartilage should be detectable on magnetic resonance imaging (MR). Enchondroma may be the precursor of chondrosarcoma; benign cartilaginous islands are often seen microscopically at the periphery of chondrosarcoma. We attempted to detect these islands at the periphery of chondrosarcomas on MR and correlate them microscopically. Materials and methods: We examined our database for all patients with a chondrosarcoma of the long and flat bones between 1990 and 2007. Only those with a preoperative MR who underwent an en bloc resection were included, yielding 32 patients. We looked for low-signal islands surrounded by high (fat) signal on T1-weighted images, and high-signal islands surrounded by low signal on T2-weighted fat saturated images at the periphery of the main tumour mass. Microscopic correlation was performed in all cases. Results: On microscopy, there were 23 conventional chondrosarcomas, nine dedifferentiated. Peripheral islands surrounded by fat were detected on MR in 19 cases, corresponding to benign cartilage in 18 cases and to the benign scar of a needle biopsy tract in one. There were no peripheral islands detected radiographically or microscopically in 13 cases. Conclusion: Cartilaginous islands microscopically detected at the periphery of some chondrosarcomas are easily and reliably diagnosed on MR.

  12. Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma.

    Directory of Open Access Journals (Sweden)

    Linda Olsson

    Full Text Available Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events.

  13. Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature patient

    International Nuclear Information System (INIS)

    Cannon, Christopher P.; Nelson, Scott D.; Seeger, Leanne L.; Eckardt, Jeffrey J.

    2002-01-01

    We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral head of a 14-year-old skeletally immature boy. Radiographic examination revealed a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the patient's age and the radiographic appearance of the lesion, chondroblastoma was high on the differential diagnosis. A frozen section was performed at the time of open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS in a skeletally immature patient was felt to be unlikely, so curettage and bone grafting was performed. Final pathology review, however, confirmed the diagnosis of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection and hemiarthroplasty. (orig.)

  14. Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature patient

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Christopher P. [Department of Orthopaedic Surgery, Madigan Army Medical Center, Ft. Lewis, WA (United States); Nelson, Scott D. [Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine, CA (United States); Seeger, Leanne L. [Department of Radiological Sciences, University of California, CA (United States); Eckardt, Jeffrey J. [Department of Orthopaedic Surgery, University of California, Los Angeles School of Medicine, CA (United States)

    2002-06-01

    We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral head of a 14-year-old skeletally immature boy. Radiographic examination revealed a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the patient's age and the radiographic appearance of the lesion, chondroblastoma was high on the differential diagnosis. A frozen section was performed at the time of open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS in a skeletally immature patient was felt to be unlikely, so curettage and bone grafting was performed. Final pathology review, however, confirmed the diagnosis of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection and hemiarthroplasty. (orig.)

  15. Review of Extraskeletal Activity on Tc-99m Methylene Diphosphonate Bone Scintigraphy and Value of Cross-Sectional and SPECT-CT Imaging Correlation.

    Science.gov (United States)

    Bermo, Mohammed; Behnia, Sanaz; Fair, Joanna; Miyaoka, Robert S; Elojeimy, Saeed

    2017-07-31

    Recognizing the different mechanisms and imaging appearance of extraskeletal Tc-99m methylene diphosphonate uptake enhances the diagnostic value of bone scan interpretation. In this article, we present a pictorial review of the different mechanisms of extraskeletal Tc-99m methylene diphosphonate uptake on bone scintigraphy including neoplastic, inflammatory, ischemic, traumatic, excretory, and iatrogenic. We also illustrate through case examples the added value of correlation with cross-sectional and single photon emission computed tomography and computed tomography imaging in localizing and characterizing challenging cases of extraskeletal uptake. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

    International Nuclear Information System (INIS)

    Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

    1982-01-01

    Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

  17. Intraosseous atypical chondroid tumor or chondrosarcoma grade 1 in patients with multiple osteochondromas.

    Science.gov (United States)

    Goud, Annemarie L; Wuyts, Wim; Bessems, Johannes; Bramer, Jos; van der Woude, Henk Jan; Ham, John

    2015-01-07

    The autosomal dominant condition multiple osteochondromas, formerly called multiple hereditary exostoses, is associated with a risk of malignant progression of osteochondroma into secondary peripheral chondrosarcoma. Most patients with multiple osteochondromas have exostosin-1 or exostosin-2 gene mutations. To our knowledge, it has not been previously reported that patients may also harbor intraosseous (central) chondroid neoplasms, enchondromas, or atypical chondroid tumors or central chondrosarcomas. The combination of osteochondroma and enchondromas also exists in patients with metachondromatosis, a disorder associated with a protein tyrosine phosphatase non-receptor type 11 gene mutation. This study aims to establish any correlation between multiple osteochondromas and intraosseous cartilaginous neoplasms. We retrospectively reviewed all histologically proven intraosseous atypical chondroid tumors or chondrosarcomas in our prospective nationwide Dutch tertiary referral multiple osteochondromas database. Demographic, clinical, radiographic, histological, and genetic data were recorded. The institutional medical ethics review board approved the study. From 195 adult patients, seven (3.6%) were identified with intraosseous atypical chondroid tumor or chondrosarcoma World Health Organization grade 1 and had a mean age of forty-two years; five of these patients were male. In all cases, radiographic and genetic findings were consistent with multiple osteochondromas, not metachondromatosis; three patients had an exostosin-1 mutation, four patients had an exostosin-2 mutation, and no patients had a protein tyrosine phosphatase, non-receptor type 11 mutation. Six patients underwent successful operative treatment without complications or recurrences after a mean follow-up duration of forty-eight months (range, twelve to 144 months). One patient was scheduled for surgery after biopsy and histologic confirmation. Of the seven patients, five (71%) also developed a

  18. Dedifferentiated chondrosarcoma with leukocytosis and elevation of serum G-CSF. A case report

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    Oda Yoshinao

    2006-07-01

    Full Text Available Abstract Background G-CSF is known to function as a hematopoietic growth factor and it is known to be responsible for leukocytosis. G-CSF-producing tumors associated with leukocytosis include various types of malignancies. Case presentation We report the case of a 72-year-old man with dedifferentiated chondrosarcoma characterized by dedifferentiated components of malignant fibrous histiocytoma- or osteosarcoma-like features in addition to conventional chondrosarcoma, arising from his pelvic bone. After hemipelvectomy, when local recurrence and metastasis were identified, leukocytosis appeared and an elevated level of serum granulocyte-colony-stimulating factor (G-CSF was also recognized. The patient died of multiple organ failure 2 months after surgery. Autopsy specimens showed that the histological specimens of the recurrence and metastasis were dedifferentiated components, without any conventional chondrosarcoma components. G-CSF was expressed only in the dedifferentiated components, not in the chondrosarcoma components, immunohistochemically. Conclusion This is the first report of chondrosarcoma, or any other primary bone tumor, with leukocytosis, probably stimulated by tumor-produced G-CSF from the dedifferentiated components.

  19. Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-Ray, Proton, Iron Ion and Carbon Ion Exposures

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    Wakatsuki, Masaru, E-mail: wa@mbe.nifty.com [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States); Magpayo, Nicole; Kawamura, Hidemasa; Held, Kathryn D. [Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States)

    2012-09-01

    Purpose: Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Methods and Materials: Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. Results: In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. Conclusions: We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.

  20. Myxoid Chondrosarcoma of Maxilla in a Pediatric Patient: A Rare Case Report

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    Pranali Nimonkar

    2016-01-01

    Full Text Available Myxoid variant of chondrosarcoma is an uncommon potentially lethal malignant tumor which is even rare in pediatric age group. In the present paper, we report one such case of intermediate grade myxoid chondrosarcoma of left side of maxilla in a 12-year-old girl. The present case had a firm, painless, and lobulated growth in premolar-molar region which was associated with bicortical expansion. Maxillofacial imaging showed ill-defined radiolucency with displaced maxillary molars. Osteolytic changes were evident with the alveolus and walls of maxillary sinus. Owing to the age of the patient, surgical excision was selected as the modality of management followed by postoperative radiotherapy. This report encompasses the entire gamut of clinicopathological, radiological, and treatment modalities employed for chondrosarcoma.

  1. Suppression of hyaluronan synthesis attenuates the tumorigenicity of low-grade chondrosarcoma.

    Science.gov (United States)

    Hamada, Shunsuke; Nishida, Yoshihiro; Zhuo, Lisheng; Shinomura, Tamayuki; Ikuta, Kunihiro; Arai, Eisuke; Koike, Hiroshi; Kimata, Koji; Ushida, Takahiro; Ishiguro, Naoki

    2017-11-01

    Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of an HA synthesis inhibitor, 4-methylumbelliferone (MU), on ECM formation as well as antitumor effects in chondrosarcoma. We investigated the effects of MU on rat chondrosarcoma (RCS) cells with a grade I histological malignancy in vitro and in vivo grafted model. HA binding protein (HABP) stainability on and around the RCS cells was effectively reduced with treatment of MU. ECM formation was markedly suppressed by MU at a dose of 1.0 mM. Cell proliferation was significantly reduced by MU at 24 h. Cell motility and invasion were suppressed in a dose-dependent manner by MU. No significant changes in mRNA expression of Has1-3 were observed. Furthermore, MU inhibited the growth of grafted tumors in vivo. Histologically, chondrosarcoma cells of control tumors showed a cell-clustering structure. HABP stainability was markedly decreased in the MU-treated group. These results suggest that MU exhibits antitumor effects on low-grade chondrosarcoma, via inhibition of HA accumulation and ECM formation. MU, which is an approved drug in bile therapy, could be a new off-label medication for chondrosarcomas. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  2. Chondrosarcoma of the hyoid bone: computed tomography findings; Condrosarcoma de hioides: hallazgos en tomografia computarizada

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    Saez, J.; Gallego, J. a.; Fuster, M. J. [Hospital General Universitario de Elche. Alicante (Spain)

    2001-07-01

    Chondrosarcoma of the hyoid bone is a rare entity, only 10 cases of which have been reported in the literature to date. the case we present involved a 24-year-old man who complained of progressive adynophagia and a mass in anterior neck. Computed tomography revealed a low-attenuation mas attached to the left horn of the hyoid bone. The lesion was excised and was diagnosed as a grade II chondrosarcoma. The patient remains asymptomatic 10 years after the operation. (Author) 11 refs.

  3. Reconstruction of Anterior Chest Wall with Polypropylene Mesh: Two Primary Sternal Chondrosarcoma Cases.

    Science.gov (United States)

    Kawana, Shinichi; Yamamoto, Hiromasa; Maki, Yuho; Sugimoto, Seiichiro; Toyooka, Shinichi; Miyoshi, Shinichiro

    2017-06-01

     Primary sternal chondrosarcoma is a rare malignant tumor that is refractory to chemotherapy and radiation. Effective therapy is radical resection of the tumor. We present two patients with primary sternal chondrosarcoma who underwent a radical resection of the lower half of the sternum and bilateral ribs, followed by reconstruction with 2 sheets of polypropylene mesh layered orthogonally. The patients have maintained almost the same pulmonary function as preoperative values, with stability of the chest wall. Although there are various ways to reconstruct the anterior chest wall, reconstruction with polypropylene mesh layered orthogonally is an easy-to-use and sufficient method.

  4. Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo

    International Nuclear Information System (INIS)

    Klenke, Frank M; Abdollahi, Amir; Bertl, Elisabeth; Gebhard, Martha-Maria; Ewerbeck, Volker; Huber, Peter E; Sckell, Axel

    2007-01-01

    As chondrosarcomas are resistant to chemotherapy and ionizing radiation, therapeutic options are limited. Radical surgery often cannot be performed. Therefore, additional therapies such as antiangiogenesis represent a promising strategy for overcoming limitations in chondrosarcoma therapy. There is strong experimental evidence that SU6668, an inhibitor of the angiogenic tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1 can induce growth inhibition of various primary tumors. However, the effectiveness of SU6668 on malignant primary bone tumors such as chondrosarcomas has been rarely investigated. Therefore, the aim of this study was to investigate the effects of SU6668 on chondrosarcoma growth, angiogenesis and microcirculation in vivo. In 10 male severe combined immunodeficient (SCID) mice, pieces of SW1353 chondrosarcomas were implanted into a cranial window preparation where the calvaria serves as the site for the orthotopic implantation of bone tumors. From day 7 after tumor implantation, five animals were treated with SU6668 (250 mg/kg body weight, s.c.) at intervals of 48 hours (SU6668), and five animals with the equivalent amount of the CMC-based vehicle (Control). Angiogenesis, microcirculation, and growth of SW 1353 tumors were analyzed by means of intravital microscopy. SU6668 induced a growth arrest of chondrosarcomas within 7 days after the initiation of the treatment. Compared to Controls, SU6668 decreased functional vessel density and tumor size, respectively, by 37% and 53% on day 28 after tumor implantation. The time course of the experiments demonstrated that the impact on angiogenesis preceded the anti-tumor effect. Histological and immunohistochemical results confirmed the intravital microscopy findings. SU6668 is a potent inhibitor of chondrosarcoma tumor growth in vivo. This effect appears to be induced by the antiangiogenic effects of SU6668, which are mediated by the inhibition of the key angiogenic receptor tyrosine kinases Flk-1/KDR, PDGFRbeta

  5. Long non-coding RNA BCAR4 promotes chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway.

    Science.gov (United States)

    Shui, Xiaolong; Zhou, Chengwei; Lin, Wei; Yu, Yang; Feng, Yongzeng; Kong, Jianzhong

    2017-05-01

    Chondrosarcoma is one of the common malignant histologic tumors, very difficult to treat, but the concrete cause and mechanism have not yet been elucidated. The present study aimed to investigate the functional involvement of BCAR4 in chondrosarcoma and its potentially underlying mechanism. QRT-PCR and western blot were used to determine the expression of BCAR4 and mTOR signaling pathway proteins both in chondrosarcoma tissues and cells. Chondrosarcoma cell proliferation and migration were assessed by MTT assay and transwell migration assay, respectively. The expression vectors were constructed and used to modulate the expression of BCAR4 and mTOR. Chondrosarcoma xenograft mouse model was established by subcutaneous injection with chondrosarcoma cell lines. The tumor volume was monitored to evaluate the effect of BCAR4 on chondrosarcoma cell tumorigenicity. The expressions of BCAR4, p-mTOR and p-P70S6K were up-regulated in chondrosarcoma tissues and cell lines. Moreover, BCAR4 overexpression had significant promoting effect on cell proliferation and migration in chondrosarcoma cells. Furthermore, mTOR signaling pathway was epigenetically activated by BCAR4-induced hyperacetylation of histone H3. We also found that mTOR overexpression abolished the decrease of chondrosarcoma cell proliferation and migration induced by BCAR4 knockdown. In vivo experiments confirmed that BCAR4 overexpression significantly accelerated tumor growth, while the knockdown of BCAR4 significantly inhibited tumor growth. BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression. Impact statement LncRNA BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression.

  6. Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature

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    Chetaille Bruno

    2010-11-01

    Full Text Available Abstract Background Low-grade extraskeletal osteosarcomas (ESOS are extremely rare. Case presentation We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of MDM2 and CDK4 oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms. Conclusion We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases.

  7. Osteosarcoma and chondrosarcoma: radiographic differentiation by means of computed tomography; Osteossarcoma e condrossarcoma - diferenciacao radiografica por meio da tomografia computadorizada

    Energy Technology Data Exchange (ETDEWEB)

    Tossato, Patricia dos Santos; Pereira, Amanda Caceres; Cavalcanti, Marcelo Gusmao Paraiso [Sao Paulo Univ., SP (Brazil). Faculdade de Odontologia. Dept. de Estomatologia

    2002-03-01

    The purpose of this paper was to associate and compare the radiographic patterns of osteosarcoma and those of chondrosarcoma by means of computed tomography (CT). Computed tomographs of five cases of osteosarcoma and five cases of chondrosarcoma of the head and neck region were analyzed. The sensitivity of CT was calculated based on the results of histopathological examinations. We concluded that CT can facilitate the establishment of the final diagnosis since it is possible to distinguish the individual characteristics of osteosarcomas and chondrosarcomas in that exam. (author)

  8. Primary bone carcinosarcoma of the fibula with chondrosarcoma and squamous cell carcinoma components.

    Science.gov (United States)

    Ishida, Mitsuaki; Kodama, Narihito; Takemura, Yoshinori; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Matsusue, Yoshitaka; Okabe, Hidetoshi

    2013-01-01

    Carcinosarcoma is defined as a malignant neoplasm that is composed of both carcinomatous and sarcomatous components. The occurrence of carcinosarcoma in the bone is extremely rare. In this report, we describe the third documented de novo case of carcinosarcoma of the bone. A 59-year-old Japanese female presented with a painful tumor in her right lower leg. Plane radiography revealed an osteolytic destructive lesion with periosteal reaction and mineralization in the right fibula. Resection of the fibula tumor was performed under a clinical diagnosis of chondrosarcoma. Histopathological study revealed that the tumor was comprised of three components. The main component was proliferation of small round to short spindle cells (approximately 50%), and the remaining components were chondrosarcoma (30%) and squamous cell carcinoma (20%). Immunohistochemically, SOX9 was expressed in the small round to spindle cells and chondrosarcoma component, and p63 and p40 were expressed in all three components. Accordingly, an ultimate diagnosis of carcinosarcoma of the bone was made. The clinicopathological analysis of carcinosarcoma of the bone revealed that this type of tumor affects the middle-aged to elderly persons and occurs in the long bone. All three de novo cases had chondrosarcoma and squamous cell carcinoma components. One of the 3 patients died of the disease. The histogenesis of carcinosarcoma of the bone remains a matter of controversy, although a multpotential stem cell theory has been proposed. Additional studies are required to clarify the clinical behavior and histogenesis of carcinosarcoma of the bone.

  9. Development and characterization of a human three-dimensional chondrosarcoma culture for in vitro drug testing.

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    Aurélien Voissiere

    Full Text Available It has been suggested that chemoresistance of chondrosarcoma (CHS, the cartilage tumor, is caused by the phenotypic microenvironmental features of the tumor tissue, mainly the chondrogenic extracellular matrix (ECM, and hypoxia. We developed and characterized a multicellular tumor spheroid (MCTS of human chondrosarcoma HEMC-SS cells to gain insight into tumor cell biology and drug response. At Day 7, HEMC-SS spheroids exhibited a homogeneous distribution of proliferative Ki-67 positive cells, whereas in larger spheroids (Day 14 and Day 20, proliferation was mainly localized in the periphery. In the core of larger spheroids, apoptotic cells were evidenced by TUNEL assay, and hypoxia by pimonidazole staining. Interestingly, VEGF excretion, evidenced by ELISA on culture media, was detectable from Day 14 spheroids, and increased as the spheroids grew in size. HEMC-SS spheroids synthesized a chondrogenic extracellular matrix rich in glycosaminoglycans and type-2 collagen. Finally, we investigated the sensitivity of Day 7 and Day 14 chondrosarcoma MCTS to hypoxia-activated prodrug TH-302 and doxorubicin compared with their 2D counterparts. As expected, TH-302 exhibited higher cytotoxic activity on larger hypoxic spheroids (Day 14 than on non-hypoxic spheroids (Day 7, with multicellular resistance index (MCRI values of 7.7 and 9.1 respectively. For doxorubicin, the larger-sized spheroids exhibited higher drug resistance (MCRI of 5.0 for Day 7 and 18.3 for Day 14 spheroids, possibly due to impeded drug penetration into the deep layer of spheroids, evidenced by its auto-fluorescence property. We have developed a model of human chondrosarcoma MCTS that combines an ECM rich in glycosaminoglycans with a high hypoxic core associated with VEGF excretion. This model could offer a more predictive in vitro chondrosarcoma system for screening drugs targeting tumor cells and their microenvironment.

  10. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

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    Dass Crispin R

    2010-06-01

    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  11. CT and Positron Emission Tomography/CT Findings of Mediastinal Extraskeletal Ewing's Sarcoma with Extensive Distant Metastasis

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    Kim, Bom Yi; Ko, Jeong Min; Park, Hyun Jin [Dept. of Radiology, St. Vincent' s Hospital, The Catholic University of Korea College of Medicine, Suwon, (Korea, Republic of)

    2012-11-15

    Extraskeletal Ewing's sarcoma (EES) is a rare aggressive malignant tumor, usually occurring in the chest wall of children and young adults. Although EES shows aggressive growth pattern, it seldom demonstrates distant metastasis at diagnosis. Herein, we present computed tomography (CT) and positron emission tomography computed tomography (PET/CT) findings of EES in anterior mediastinum in a 68-year-old man, showing multi-organ distant metastasis at diagnosis. It is another atypical case with unusual presentation in point of old age, mediastinal location and distant metastasis at diagnosis, showing PET/CT findings.

  12. CT and Positron Emission Tomography/CT Findings of Mediastinal Extraskeletal Ewing's Sarcoma with Extensive Distant Metastasis

    International Nuclear Information System (INIS)

    Kim, Bom Yi; Ko, Jeong Min; Park, Hyun Jin

    2012-01-01

    Extraskeletal Ewing's sarcoma (EES) is a rare aggressive malignant tumor, usually occurring in the chest wall of children and young adults. Although EES shows aggressive growth pattern, it seldom demonstrates distant metastasis at diagnosis. Herein, we present computed tomography (CT) and positron emission tomography computed tomography (PET/CT) findings of EES in anterior mediastinum in a 68-year-old man, showing multi-organ distant metastasis at diagnosis. It is another atypical case with unusual presentation in point of old age, mediastinal location and distant metastasis at diagnosis, showing PET/CT findings.

  13. 1-Benzyl-2-Phenylbenzimidazole (BPB, a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways

    Directory of Open Access Journals (Sweden)

    Ju-Fang Liu

    2012-12-01

    Full Text Available In this study, we investigated the anticancer effects of a new benzimidazole derivative, 1-benzyl-2-phenyl -benzimidazole (BPB, in human chondrosarcoma cells. BPB-mediated apoptosis was assessed by the MTT assay and flow cytometry analysis. The in vivo efficacy was examined in a JJ012 xenograft model. Here we found that BPB induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 but not in primary chondrocytes. BPB induced upregulation of Bax, Bad and Bak, downregulation of Bcl-2, Bid and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. In addition, BPB also promoted cytosolic releases AIF and Endo G. Furthermore, it triggered extrinsic death receptor-dependent pathway, which was characterized by activating Fas, FADD and caspase-8. Most importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 days of treatment. Thus, BPB may be a novel anticancer agent for the treatment of chondrosarcoma.

  14. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    OpenAIRE

    Ihab Shafek Atta; Fahd Nasser AlQahtani

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 7...

  15. Low-grade chondrosarcoma vs enchondroma: challenges in diagnosis and management

    International Nuclear Information System (INIS)

    Wang, X.L.; De Beuckeleer, L.H.; De Schepper, A.M.A.; Van Marck, E.

    2001-01-01

    A 28-year-old man presented with a swelling at the right thoracic wall. Computed tomography showed an aggressive process involving the cortex of the rib with concomitant soft tissue mass. However, a needle biopsy specimen revealed an enchondroma and consequently the physician decided to apply a ''wait-and-see'' strategy. After 3 years of careful follow-up by MR imaging, the patient complained of subtle enlargement of the lesion, which was later confirmed on repeated CT scan. Despite an aggressive appearance on control MR imaging, histopathological examination after incisional biopsy could not differentiate between enchondroma and low-grade chondrosarcoma. Wide excision including previous biopsy trajectory was performed. Diagnosis of a low-grade (grade I) chondrosarcoma was made on findings of the excisional specimen and seeding of cartilage tissue along the previous incisional biopsy trajectory was found. (orig.)

  16. Low-grade chondrosarcoma of the cricoid cartilage: a case report and review of the literature

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    Gao, Chuan-Ping; Liu, Ji-Hua; Xu, Wen-Jian [The Affiliated Hospital of Qingdao University, Department of Radiology, Qingdao (China); Hou, Feng [The Affiliated Hospital of Qingdao University, Department of Pathology, Qingdao (China); Liu, Hua [The Shinanqu People Hospital, Department of Radiology, Qingdao (China)

    2017-11-15

    We report the case of a 60-year-old man with a 12-day history of vomiting whenever he had a meal. Computed tomography revealed a calcified mass in the right cricoid cartilage with intraluminal and extraluminal extension. The patient underwent surgical resection of the trachea with end-to-end anastomosis. Pathological examination of the surgical specimen showed a low-grade chondrosarcoma. Eighteen months after surgery, the patient is alive and disease-free. (orig.)

  17. Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas. In vitro and in vivo correlation.

    Science.gov (United States)

    Multhaupt, H A; Alvarez, J C; Rafferty, P A; Warhol, M J; Lackman, R D

    2001-01-01

    Clinical and in vitro studies have demonstrated that fluoroquinolones are toxic to chondrocytes; however, the exact mechanism of fluoroquinolone arthropathy is unknown. We investigated the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors. Normal human cartilage, enchondroma, and chondrosarcoma explants were cultured either alone or with the addition of ciprofloxacin at 1, 10, or 20 mg/L of medium. Samples were collected up to twenty-one days after treatment and were processed for electron microscopy and conventional light microscopy. The specimens were characterized morphologically with use of conventional light microscopy, electron microscopy, and immunohistochemistry to identify extracellular matrix, cell proliferation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron microscopy revealed a large amount of glycogen in the cells; the presence of fat droplets, rough endoplasmic reticulum, and prominent Golgi apparatus; and a proteoglycan layer surrounding the cells. With prolonged ciprofloxacin treatment and with increased doses, there was an increase in dilated rough endoplasmic reticulum, the appearance of phagosomes, and disintegrated bundles of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the expression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma cultures and tissue samples showed changes in cartilage matrix composition. Ultrastructural analysis demonstrated clumped glycogen, dilation of endoplasmic reticulum, numerous abnormal lysosomes containing degeneration products, and a decreased proteoglycan deposit surrounding the tumor cells. Treated chondrosarcoma cells and tissue specimens did not proliferate, and apoptosis was induced. In contrast, the in vitro growth of other noncartilaginous malignant tumors like osteosarcoma and liposarcoma was unaffected by ciprofloxacin. Our results

  18. Rare Case of a Chondrosarcoma of the Mandible in a Child

    Directory of Open Access Journals (Sweden)

    Hendryk Vieweg

    2013-01-01

    Full Text Available Chondrosarcoma of the mandible is rare, especially in children. The available literature consists mostly of a few case reports which are partly integrated in small studies. Growing this small pool of literature is helpful in solidifying knowledge about this disease and facilitating appropriate treatment for children. Therefore, we present such a case in a 12-year-old boy, exhibit comprehensive and relevant information concerning this entity, and discuss our findings in the context of other publications.

  19. Maffucci syndrome and intracranial chondrosarcomas: a case report featuring spontaneous resolution of sixth nerve palsy.

    Science.gov (United States)

    Munro, Monique; Costello, Fiona; Burrowes, David; Yau, Ryan

    2015-03-01

    Maffucci syndrome is a rare disease process characterized by enchondromatosis with cutaneous hemangiomatosis. We report a 20-year-old woman with Maffucci syndrome with a 5-day history of diplopia. She was found to have a left sixth nerve palsy due to a parasellar chondrosarcoma. Three weeks later, the patient's diplopia spontaneously resolved. This unusual clinical course prompted us to review frequency of sixth nerve palsy with skull base neoplasms and the phenomenon of spontaneous resolution of diplopia.

  20. Diagnostic difficulties and delays with chest wall chondrosarcoma: a Swedish population based Scandinavian Sarcoma Group study of 106 patients.

    Science.gov (United States)

    Widhe, Björn; Bauer, Henrik C F

    2011-04-01

    Bone sarcomas in Sweden are generally referred to a multidisciplinary team at specialized sarcoma centers. This practice is strictly followed for sarcomas of long bones, but not for chest wall chondrosarcomas. Delay in diagnosis and treatment is often considerable for bone sarcomas. This report focuses on the symptoms and diagnostic problems of chest wall chondrosarcoma and factors related to long doctor's delay. The material included all 106 consecutive patients with chondrosarcoma of the chest wall diagnosed in Sweden 1980-2002. Pathological specimens were re-evaluated and graded by the Scandinavian Sarcoma Group pathology board. Files from the very first medical visit for symptoms related to the chondrosarcoma were traced and used to characterize the initial symptoms and calculate patient's and doctor's delay. The most prominent initial symptom for the chest wall chondrosarcomas was a palpable mass found in 69% (73/106) of the patients at the first visit. Two-thirds of the patients experienced no local chest pain. A tumor was suspected at the first visit in 83% of the patients. Patients delay was median 3 (0-118) months and doctor's delay was 4.5 (0.1-197) months. Doctor's delay was >6 months for 40% of the patients. Patients with an initial plain chest radiograph interpreted as normal (35 patients), and/or normal or inconclusive results of a fine-needle aspiration biopsy had longer doctor's delay. Fine-needle aspiration cytology done at non-specialty units resulted in only 26% correct malignant diagnoses; at sarcoma centers 94% were correctly diagnosed. Long total delay was unfavorable. Patients who died from the chondrosarcoma had longer total delay (pChest wall chondrosarcoma presents as a lump, usually painless. Plain chest radiographs and fine-needle aspiration cytology, when done at a non-specialty center, are often normal or inconclusive. Patients should be referred to sarcoma centers for diagnosis and treatment.

  1. Osteocalcin and osteonectin immunoreactivity in extraskeletal osteosarcoma: a study of 28 cases.

    Science.gov (United States)

    Fanburg-Smith, J C; Bratthauer, G L; Miettinen, M

    1999-01-01

    Extraskeletal osteosarcoma (EOSA), a rare malignant soft tissue tumor, is by definition unattached to the skeleton and composed of malignant cells of osteoblastic phenotype which produce osseous matrix (ie, neoplastic bone). Because of its location, it can mimic other soft tissue tumors, and its matrix can be mistaken for hyalinized collagen. Antiosteocalcin (OC) and antiosteonectin (ON), antibodies against two abundant human bone proteins, are explored in the diagnosis of EOSA. Twenty-eight cases coded as EOSA (n=24) or probable EOSA (n = 4) were identified from the Soft Tissue Registry of the Armed Forces Institute of Pathology (Washington DC). All cases had paraffin blocks available for immunohistochemistry. OC and ON (Biodesign International, Kennebunk, ME, clones OC1 and OST1) immunostaining for tumor cells and matrix was graded on a four-tiered grading system: 1 = focal ( or = 50%) weak staining; and 4 = diffuse strong staining. Patient ages ranged from 9 to 80 years, with a mean age of 57 years. There were 9 female patients and 19 male patients. The tumor sizes ranged from 1.5 to 15 centimeters, with a mean size of 5.8 centimeters. Locations included the lower extremity (n=14), trunk (n=9), upper extremity (n=4), and head and neck (n=1). Subtypes included 12 osteoblastic, 4 fibroblastic, 2 chondroblastic, 2 well differentiated, 1 telangiectatic, 1 small cell, and 6 giant cell rich EOSAs; the latter resembled giant cell rich malignant fibrous histiocytomas with neoplastic bone formation. All tumors had both neoplastic cells and bony tumor matrix to evaluate. OC was 82% sensitive for EOSA neoplastic cells (1 to 4+), with immunostaining of neoplastic cells away from bone in 91% of cases, and 75% for bony tumor matrix (2 to 4+). ON was 93% sensitive for EOSA neoplastic cells (2 to 4+), yet only 39% for bony tumor matrix (1 to 4+). In 100% giant cell rich EOSA, neoplastic cells were positive for OC and ON (2 to 4+). OC showed 100% specificity for osteoblasts as

  2. Laryngeal chondrosarcoma of the arytenoid cartilage presenting as bilateral vocal fold immobility: a case report and literature review.

    Science.gov (United States)

    Hu, Rong; Xu, Wen; Liu, Honggang; Chen, Xuejun

    2014-01-01

    To describe an atypical case of laryngeal chondrosarcoma of arytenoid cartilage presenting as bilateral vocal fold immobility and to avoid potential missed diagnosis. Our case study included a detail history, physical and radiological examination, laryngeal electromyography (LEMG), and surgical treatment and pathology analysis. We compared it with the previously discussed cases of chondrosarcoma of arytenoid cartilage in the literature. Chondrosarcomas of the arytenoid cartilage is rare, and to date only approximately 10 cases have been reported. We reported a case of a 51-year-old man with 1 month of persistent dyspnea presenting with bilateral vocal fold immobility without neoplasms in larynx. The LEMG showed no obvious abnormality. The cervical-enhanced computed tomography (CT) found no significant signs of a mass except for localized high-density areas in arytenoid cartilage. Right arytenoidectomy and biopsy were performed under general anesthesia with CO2 laser with the pathological diagnosis of chondroma. A total laryngectomy was performed 2 years later, and low-grade chondrosarcoma was the final diagnosis. Laryngeal chondrosarcomas of the arytenoid cartilage are rare. It is easily neglected, especially in those cases presenting with idiopathic vocal fold immobility without any obvious signs of neoplasms. The LEMG and laryngeal CT are necessary. Sometimes, a biopsy of the arytenoid cartilage is essential. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  3. Clinicopathological significance of p16, cyclin D1, Rb and MIB-1 levels in skull base chordoma and chondrosarcoma

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    Jun-qi Liu

    2015-09-01

    Full Text Available Objective: To investigate the expression of p16, cyclin D1, retinoblastoma tumor suppressor protein (Rb and MIB-1 in skull base chordoma and chondrosarcoma tissues, and to determine the clinicopathological significance of the above indexes in these diseases. Methods: A total of 100 skull base chordoma, 30 chondrosarcoma, and 20 normal cartilage tissue samples were analyzed by immunohistochemistry. The expression levels of p16, cyclinD1, Rb and MIB-1 proteins were assessed for potential correlation with the clinicopathological features. Results: As compared to normal cartilage specimen (control, there was decreased expression of p16, and increased expression of cyclin D1, Rb and MIB-1 proteins, in both skull base chordoma and chondrosarcoma specimens. MIB-1 LI levels were significantly increased in skull base chordoma specimens with negative expression of p16, and positive expression of cyclin D1 and Rb (P  0.05. However, p16 and MIB-1 levels correlated with the intradural invasion, and expression of p16, Rb and MIB-1 correlated with the number of tumor foci (P < 0.05. Further, the expression of p16 and MIB-1 appeared to correlate with the prognosis of patients with skull base chordoma. Conclusions: The abnormal expression of p16, cyclin D1 and Rb proteins might be associated with the tumorigenesis of skull base chordoma and chondrosarcoma. Keywords: p16, Cyclin D1, Rb, MIB-1, Skull base chordoma, Skull base chondrosarcoma

  4. Evaluating the Role of PTH in Promotion of Chondrosarcoma Cell Proliferation and Invasion by Inhibiting Primary Cilia Expression

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    Wei Xiang

    2014-10-01

    Full Text Available Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84, and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma.

  5. Subglottic Chondrosarcoma Presenting Only Mild Acute-Onset Dyspnea: A Case Report and Review of the Literature

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    Su-wei Tsai

    2014-01-01

    Full Text Available Chondrosarcoma is categorized as a malignant cartilaginous tumor, which occurs rarely in the craniofacial region. We report the case of a 68-year-old man with chondrosarcoma in the subglottic area. His chief symptoms were hoarseness and mild dysphagia. A computed tomography scan revealed a lesion with expansion of the cricoid cartilage and marked reduction of the airway. After biopsy, histological inspection showed that chondrocytes are multi-nucleus, their size does not differ much and mitosis is not obvious. These are all characteristics of a low-grade chondrosarcoma. We performed an organ-preserving operation by debulking the low-grade malignant tumor in order to keep a patent airway. No further metastasis or airway compromise was evident during the 1-year follow-up visit.

  6. Chondrosarcoma secondary to hereditary multiple exostosis treated by extended internal hemiplevectomy

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    Ademar Lopes

    Full Text Available The authors report on the case of a 28-year-old patient with extensive chondrosarcoma of the left ischium and pubis involving hip joint, skin, and soft tissue of the gluteal region, secondary to hereditary multiple exostosis submitted to an extended internal Enneking type II and Ill hemipelvectomy. No prosthesis or arthrodesis was used. A few years ago, patients with extensive tumors like this one were treated with interilioabdominal amputation, resulting in a loss of quality of Iife.Two years after the limb-preserving surgery, this patient was disease free, with good functional results, including bipedal ambulation with support.

  7. Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas. In vitro and in vivo correlation

    DEFF Research Database (Denmark)

    Multhaupt, H A; Alvarez, J C; Rafferty, P A

    2001-01-01

    with use of conventional light microscopy, electron microscopy, and immunohistochemistry to identify extracellular matrix, cell proliferation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron microscopy revealed a large amount of glycogen in the cells; the presence of fat...... of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the expression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma cultures and tissue samples showed changes in cartilage matrix composition...

  8. Berberine Reduces the Metastasis of Chondrosarcoma by Modulating the αvβ3 Integrin and the PKCδ, c-Src, and AP-1 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Chi-Ming Wu

    2013-01-01

    Full Text Available Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis, especially to the lungs. Patients diagnosed with chondrosarcoma have poor prognosis. Berberine, an active component of the Ranunculaceae and Papaveraceae families of plant, has been proven to induce tumor apoptosis and to prevent the metastasis of cancer cells. However, the effects of berberine in human chondrosarcoma are largely unknown. In this study, we found that berberine did not induce cell apoptosis in human primary chondrocytes and chondrosarcoma cells. However, at noncytotoxic concentrations, berberine reduced the migration and invasion of chondrosarcoma cancer cells. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. We also found that incubation of chondrosarcoma cells with berberine reduced mRNA transcription for, and cell surface expression of, the αvβ3 integrin, with additional inhibitory effects on PKCδ, c-Src, and NF-κB activation. Thus, berberine may be a novel antimetastasis agent for the treatment of metastatic chondrosarcoma.

  9. Conservative surgery for laryngeal chondrosarcoma: a review of the most recently proposed approaches.

    Science.gov (United States)

    Piazza, Cesare; Paderno, Alberto; Nicolai, Piero

    2017-04-01

    The aim of this study was to describe the most recent technical nuances for resection and reconstruction of Grade 1 and 2 laryngeal chondrosarcomas, with a special emphasis on those located at the level of the cricoid plate, which is the site of origin of the vast majority of these rare tumours. Even though inherently based on retrospective small clinical series or anecdotal case reports, a number of studies have been recently published focusing on conservative transoral and open-neck surgical procedures aimed at an oncologically sound removal of the tumour together with organ and function preservation. The open-neck conservative approaches herein reported can be roughly distinguished in those achieving a primary airway reconstruction by a tracheo-hyoido-epiglottopexy or an end-to-end crico-tracheal, thyro-crico-tracheal or thyro-tracheal anastomosis, and those requiring a single or double-staged transposition of different microvascular flaps, with or without cartilaginous graft insertion, to reconstruct a subtotal/total cricoidectomy and obtain a rigid and stable subglottic airway. No meaningful comparison in terms of oncologic and functional outcomes is still possible among the currently available conservative surgical strategies, due to the rarity of laryngeal chondrosarcomas and the heterogeneity of treatments proposed in the literature. However, a reasonable algorithm to approach this difficult clinical entity according to its site of origin and extent of cricoid circumference involved is herein presented.

  10. Enchondroma versus Low-Grade Chondrosarcoma in Appendicular Skeleton: Clinical and Radiological Criteria

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    Eugenio M. Ferrer-Santacreu

    2012-01-01

    Full Text Available Objectives. To determine the validity of clinical and radiological features of enchondroma and low grade chondrosarcoma, and contrast the biopsy results with the clinical diagnosis based on the history and imaging. Material and Method. The study included 96 patients with cartilage type lesions suggestive of an enchondroma (E or an low grade chondrosarcoma (LGC according to the clinical and imaging data. The hypotheses were contrasted with the biopsy. Results. Of the 82 patients studied completely, 56 were considered E (68.29%, 8 as LGC (8.33% and in 18 (18.75% were doubtful cases and considered as suspected LGC. Of these, the biopsy showed 4 E (25%, 10 LGC (50% and 4 were not definitive. On the other hand, of the 56 cases diagnosed as E, 15 were biopsied, 5 of these biopsies turned out to be LGC (33.3%. The 8 cases diagnosed as LGC, were also biopsied and only 4 biopsies (50% confirmed the initial diagnosis. Features analyzed in the study showed no statistically significant difference. Correlation analysis between the diagnosis issued initially and the biopsy result gave a value of 0.69 (kappa coefficient, which was considered a good correlation. Conclusion. Features analyzed did not have any statistical significance. However, there was a good correlation between initial diagnosis and biopsy's result.

  11. Internal hemipelvectomy with intraoperative and external beam radiotherapy in the limb-sparing treatment of a pelvic girdle chondrosarcoma

    NARCIS (Netherlands)

    Hoekstra, HJ; Szabo, BG

    The case of a patient with an extensive pelvic girdle chondrosarcoma treated with internal hemipelvectomy and intraoperative radiotherapy, followed by adjuvant high-dose external beam radiotherapy, with a successful attempt in achieving long-term local tumor control and limb-sparing treatment is

  12. Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity.

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    Christopher A Hamm

    Full Text Available Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells.

  13. Mast Cells Density in Fibrotic Capsule of Enchondroma and Well-Differentiated Chondrosarcoma: A Method for Histopathologic Differentiation

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    Mohammad Javad Kharazi Fard

    2012-02-01

    Full Text Available Background: An enchondroma is a benign and a well-differentiated chondrosarcoma is an invasive chondroid tumor with high recurrence potential. In spite of biologic differences, these two tumors have very similar histopathologic appearance. It has been shown that the biologic nature of the connective tissue around benign and malignant tumors varies in the number of mast cells. The aim of this study was to study the histopathologic distinction of enchondroma and well-differentiated chondrosarcoma using the density of the mast cells in fibrotic capsule. Methods: Twelve enchondroma and 15 well-differentiated chondrosarcoma were collected from Pathology department of Cancer Institute and Central Pathology department of Imam Khomeini Hospital in Tehran. 3 micron paraffin embedded tissue sections were stained by toluidine blue for mast cells counting. Mast cells were counted in fibrous capsule of all cases. Mast cells counts were accomplished in 10 high power fields .The average number of mast cells in 10HPF was determined as an index for each lesion. Mann-Whitney U test was used for statistical analysis. Results: Mean index in enchondroma and well-differentiated chondrosarcoma groups were 0.1±0.12 and 0.31±0.33 respectively, showing a significant difference between number of mast cells in the fibrotic capsule in these two lesions (p=0.028. Comparison of the corresponding points in ROC curve, showed a cut-off point = 0.15, with positive predictive value of 61%, negative predictive value 71%, specificity of 33.3% and sensitivity of 66.7%, (p=0.025. Conclusion: Average density of the mast cells in the surrounding fibrotic capsules of enchondroma and well-differentiated chondrosarcoma along with other criterions, could be a beneficial factor for histologically differentiation between these two lesions.

  14. A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine

    Energy Technology Data Exchange (ETDEWEB)

    Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Rotondo, Ronny L.; Begosh-Mayne, Dustin [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Scarborough, Mark T.; Gibbs, C. Parker [Department of Orthopedics and Rehabilitation, University of Florida College of Medicine, Gainesville, Florida (United States); Morris, Christopher G.; Mendenhall, William M. [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States)

    2016-05-01

    Purpose: To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine. Methods and Materials: Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Results: The mean follow-up time was 3.7 years (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1). Conclusion: High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by

  15. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

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    Luyuan Li

    Full Text Available Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2 were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas.

  16. An Evaluation of the Diagnostic Accuracy of the Grade of Preoperative Biopsy Compared to Surgical Excision in Chondrosarcoma of the Long Bones

    Directory of Open Access Journals (Sweden)

    Robert Jennings

    2010-01-01

    Full Text Available Chondrosarcoma is the second most common primary malignant bone tumour. Distinguishing between grades is not necessarily straightforward and may alter the disease management. We evaluated the correlation between histological grading of the preoperative image-guided needle biopsy and the resection specimen of 78 consecutive cases of chondrosarcoma of the femur, humerus, and tibia. In 11 instances, there was a discrepancy in histological grade between the biopsy and surgical specimen. Therefore, there was an 85.9% (67/78 accuracy rate for pre-operative histological grading of chondrosarcoma, based on needle biopsy. However, the accuracy of the diagnostic biopsy to distinguish low-grade from high-grade chondrosarcoma was 93.6% (73/78. We conclude that accurate image-guided biopsy is a very useful adjunct in determining histological grade of chondrosarcoma and the subsequent treatment plan. At present, a multidisciplinary approach, comprising experienced orthopaedic surgeons, radiologists, and pathologists, offers the most reliable means of accurately diagnosing and grading of chondrosarcoma of long bones.

  17. Oncological outcome after lung metastasis in patients presenting with localized chondrosarcoma at extremities: Tokai Musculoskeletal Oncology Consortium study

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    Nakamura T

    2016-07-01

    Full Text Available Tomoki Nakamura,1 Akihiko Matsumine,1 Satoshi Yamada,2 Satoshi Tsukushi,3,4 Katsuhisa Kawanami,5 Takatoshi Ohno,6 Hirohisa Katagiri,7 Hideshi Sugiura,3,8 Kenji Yamada,9 Yoshihisa Yamada,10 Akihiro Sudo,1 Yoshihiro Nishida4 1Department of Orthopaedic Surgery, Mie Graduate School of Medicine, Tsu-City, Mie, 2Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, 3Department of Orthopedic Surgery, Aichi Cancer Center Hospital, 4Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 5Department of Orthopaedic Surgery, Aichi Medical University School of Medicine, Nagakute, 6Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, 7Division of Orthopaedic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi, Shizuoka, 8Department of Physical Therapy, Nagoya University Graduate School Medicine, Nagoya, 9Department of Orthopedic Surgery, Aichi Cancer Center, Aichi Hospital, Okazaki, 10Department of Orthopedic Surgery, Nagoya Memorial Hospital, Nagoya, Aichi, Japan Abstract: The oncological outcome after lung metastasis in patients with chondrosarcoma of the extremities has not been reported. Between June 2000 and June 2013, 179 patients with chondrosarcoma in the extremities were treated at eleven hospitals. Twenty consecutive patients (11.2% developed lung metastases after initial treatment of primary chondrosarcoma in the extremities. We investigated the oncological outcome of 20 chondrosarcoma patients with lung metastasis. There were 14 males and six females with a mean age of 49 years. The mean duration between primary surgery and appearance of lung metastases was 34 months. The mean follow-up period was 48 months. We excluded patients with lung metastasis at the time of presentation from this study. At the final follow-up, four of 20 patients had no evidence of disease, four were alive with disease, and twelve had died of disease. The

  18. Extraskeletal osteosarcoma in the neck. A case report and review of the literature; Osteosarcoma extra-esqueletico na regiao cervical. Revisao de literatura e relato de caso clinico

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    Lima, Jose Jorge Gomes; Silva, Fabio Luis da [Santa Casa de Misericordia, Piracicaba, SP (Brazil). Centro de Tomografia Computadorizada; Manzi, Flavio Ricardo [Pontificia Univ. Catolica de Minas Gerais, Belo Horizonte, MG (Brazil). Radiologia Odontologica]. E-mail: flaviomanzi@hotmail.com; Baptista, Mauricio Zuccollotto [Santa Casa de Misericordia, Piracicaba, SP (Brazil). Inst. de Oncologia Clinica

    2002-10-01

    Extra skeletal osteosarcoma is a rare neoplasm characterized by the formation of a malignant osteoid. This condition is usually described in patients aged greater than expected for other intraosseous osteosarcomas, and the thigh is the most common site. We report a clinical case of a 19-year-old female patient and review the literature. The patient present with a mass in the right side of the neck and paraesthesia of the upper limbs. The mass corresponded to an extraskeletal osteosarcoma. We discuss the clinical findings, image findings (conventional radiographs, computed tomography, magnetic resonance imaging), histopathology results and differential diagnosis of this condition. (author)

  19. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    Directory of Open Access Journals (Sweden)

    Ihab Shafek Atta

    2016-01-01

    Full Text Available We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner’s, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A.

  20. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    Science.gov (United States)

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  1. A “Proteoglycan Targeting Strategy” for the Scintigraphic Imaging and Monitoring of the Swarm Rat Chondrosarcoma Orthotopic Model

    Directory of Open Access Journals (Sweden)

    Caroline Peyrode

    2011-01-01

    Full Text Available Our lab developed 99mTc-NTP 15-5 radiotracer as targeting proteoglycans (PGs for the scintigraphic imaging of joint. This paper reports preclinical results of 99mTc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC. 99mTc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume. Tumours were characterized by histology and PG assay. SRC exhibited a significant 99mTc-NTP 15-5 uptake at very early stage after implant (with tumour/muscle ratio of 1.61 ± 0.14, whereas no measurable tumour was evidenced. As tumour grew, mean tumour/muscle ratio was increased by 2.4, between the early and late stage of pathology. Bone scintigraphy failed to image chondrosarcoma, even at the later stage of study. 99mTc-NTP 15-5 imaging provided a suitable set of quantitative criteria for the in vivo characterization of chondrosarcoma behaviour in bone environment, useful for achieving a greater understanding of the pathology.

  2. Intralesional curettage and cementation for low-grade chondrosarcoma of long bones: retrospective study and literature review.

    Science.gov (United States)

    Mermerkaya, Musa Ugur; Bekmez, Senol; Karaaslan, Fatih; Danisman, Murat; Kosemehmetoglu, Kemal; Gedikoglu, Gokhan; Ayvaz, Mehmet; Tokgozoglu, Ahmet Mazhar

    2014-11-10

    Various treatment strategies for low-grade chondrosarcomas with variable outcomes have been reported in the literature. The aim of this study was to assess the oncological and functional outcomes associated with intralesional curettage followed by adjuvant therapy comprising high-speed burring, thermal cauterization, and bone cementation with polymethylmethacrylate. We performed a retrospective review of 21 consecutive patients with intramedullary low-grade chondrosarcoma of long bones treated by intralesional curettage and adjuvant therapy comprising high-speed burring, thermal cauterization, and cementation at our institution from 2007 to 2012. The average age of the patients was 48.7 (range, 18-71) years. There were 7 male and 14 female patients. The mean follow-up period was 58.4 (range, 26-85) months after surgery. The treated lesions were located in the proximal humerus (n=10), proximal tibia (n=6), and distal femur (n=5). At the average follow-up time point of 58.4 (range, 26-85) months, no patient had developed local recurrence and no distant metastases were observed. The average Musculoskeletal Tumor Society score among all 21 patients was 95% (84-100). The combination of intralesional curettage, application of high-speed burring, thermal cauterization, and cementation is an effective treatment strategy for low-grade intramedullary chondrosarcoma of long bones. Excellent oncological and functional results can be obtained.

  3. Mesenchymal breast lesions

    International Nuclear Information System (INIS)

    Schickman, R.; Leibman, A.J.; Handa, P.; Kornmehl, A.; Abadi, M.

    2015-01-01

    Mesenchymal breast lesions encompass a variety of breast diseases. Many of these lesions are rare with only a few case reports in the literature. This article reviews the imaging findings of selected mesenchymal breast lesions, their clinical presentations and method of diagnosis. Mesenchymal lesions are diverse and include haemangioma, granular cell tumour, myofibroblastoma, fibromatosis, pseudoangiomatous stromal hyperplasia, and malignant fibrous histiocytoma. It is important for radiologists to be aware of these lesions as some of them may have malignant potential or demonstrate imaging features that overlap with other malignant lesions

  4. 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.

  5. The Use of a Custom-made Prosthesis in the Treatment of Chondrosarcoma of Distal Radius.

    Science.gov (United States)

    Guzik, Grzegorz

    2016-01-01

    The most common neoplasms of the distal radius are primary tumors, of which aneurysmal bone cysts and giant cell tumors are seen almost exclusively. Chondrosarcomas are most commonly located in the pelvis, ribs and proximal segments of the extremities; they rarely occur in forearm bones. Bone defects after distal radial resection can be replaced with bone grafts, both autogenous and allogenic. There is always a risk of failure of the bones to mend or slower synostosis, which necessitates the search for new treatments. Recently, custom-made prostheses have been used with increasing frequency. In early 2015, a 25-year-old male patient was admitted to the Department of Orthopedic Oncology in Brzozów on account of a tumor involving the epiphysis and metaphysis of the right distal radius. Imaging studies confirmed that the lesion was a neoplasm and a biopsy revealed a chondrosarcoma. Radical resection of the tumor was attempted and a custom-made prosthesis was inserted in the place of the bone defect. The prosthesis was designed and manufactured over 4 weeks. No complications occurred during the surgery or in the postoperative period. After the surgery, the forearm and wrist were in a plaster splint for 6 weeks and then rehabilitation was started. The treatment outcome was good. Now, three months after the surgery, the patient has good wrist mobility and efficient grip. Surgical treatment of malignant tumors of the distal radius with extensive bone resection poses the challenge of bone replacement and recovery of fair hand function. Commonly known and practised, reconstructions with autogenous or allogenic bone grafts enable partial restoration of the radiocarpal joint surface and DRUJ. The use of large bone grafts is associated with a risk of non-union and limited hand function even if the grafts are vascularized. Arthrodesis of the radiocarpal joint is currently performed less and less frequently. Custom-made prostheses appear to be a good solution. This method makes

  6. Condrossarcoma mixóide de átrio direito Right atrium myxoid chondrosarcoma

    Directory of Open Access Journals (Sweden)

    Cláudio Ribeiro da Cunha

    2008-03-01

    Full Text Available Relatamos o caso de uma paciente de 46 anos, cor branca, hipertensa há 20 anos, com suspeita de endocardite infecciosa. Foi realizado ecocardiograma transtorácico, o qual levou à hipótese de mixoma de átrio direito. A paciente foi submetida à cirurgia, observando-se massa tumoral de aspecto muco-gelatinoso friável. A massa foi submetida a congelação para exame anatomopatológico, com laudo sugestivo de tumor maligno mesenquimal. Foi realizado exame imunohistoquímico compatível com condrossarcoma mixóide. A paciente evoluiu com remissão espontânea do quadro após ressecção completa da neoplasia. Realizou acompanhamento ambulatorial por 14 meses, sem apresentar sinais de recidiva do tumor.We report a case of a 46 years-old woman, Caucasian, with hypertension and a primary dianosis of infectious endocarditis. A transthoracic echocardiogram was performed suggesting right atrium myxoma. The patient was submitted to surgery, which found a tumor mass with a jelly-like exterior. The mass was sent to anatomo-pathological analysis which diagnosed a myxoid chondrosarcoma tumor. After surgical resection, the patient achieved complete recovery with no signs of recidivation after 14 months.

  7. Recurrent and self-remitting sixth cranial nerve palsy: pathophysiological insight from skull base chondrosarcoma.

    Science.gov (United States)

    Frassanito, Paolo; Massimi, Luca; Rigante, Mario; Tamburrini, Gianpiero; Conforti, Giulio; Di Rocco, Concezio; Caldarelli, Massimo

    2013-12-01

    Palsy of the abducens nerve is a neurological sign that has a wide range of causes due to the nerve's extreme vulnerability. Need of immediate neuroimaging is a matter of debate in the literature, despite the risks of delaying the diagnosis of a skull base tumor. The authors present 2 cases of skull base tumors in which the patients presented with recurrent and self-remitting episodes of sixth cranial nerve palsy (SCNP). In both cases the clinical history exceeded 1 year. In a 17-year-old boy the diagnosis was made because of the onset of headache when the tumor reached a very large size. In a 12-year-old boy the tumor was incidentally diagnosed when it was still small. In both patients surgery was performed and the postoperative course was uneventful. Pathological diagnosis of the tumor was consistent with that of a chondrosarcoma in both cases. Recurrent self-remitting episodes of SCNP, resembling transitory ischemic attacks, may be the presenting sign of a skull base tumor due to the anatomical relationships of these lesions with the petroclival segment of the sixth cranial nerve. Physicians should promptly recommend neuroimaging studies if SCNP presents with this peculiar course.

  8. In vitro evaluation of chondrosarcoma cells and canine chondrocytes on layer-by-layer (LbL) self-assembled multilayer nanofilms

    International Nuclear Information System (INIS)

    Shaik, J; Mohammed, J Shaikh; McShane, M J; Mills, D K

    2013-01-01

    Short-term cell–substrate interactions of two secondary chondrocyte cell lines (human chondrosarcoma cells, canine chondrocytes) with layer-by-layer self-assembled multilayer nanofilms were investigated for a better understanding of cellular-behaviour dependence on a number of nanofilm layers. Cell–substrate interactions were studied on polyelectrolyte multilayer nanofilms (PMNs) of eleven different biomaterials. Surface characterization of PMNs performed using AFM showed increasing surface roughness with increasing number of layers for most of the biomaterials. LDH-L and MTT assays were performed on chondrosarcoma cells and canine chondrocytes, respectively. A major observation was that 10-bilayer nanofilms exhibited lesser cytotoxicity towards human chondrosarcoma cells than their 5-bilayer counterparts. In the case of canine chondrocytes, BSA enhanced cell metabolic activity with increasing number of layers, underscoring the importance of the multilayer nanofilm architecture on cellular behaviour. (paper)

  9. Imaging Features of Primary Tumors and Metastatic Patterns of the Extraskeletal Ewing Sarcoma Family of Tumors in Adults: A 17-Year Experience at a Single Institution.

    Science.gov (United States)

    Huh, Jimi; Kim, Kyung Won; Park, Seong Joon; Kim, Hyoung Jung; Lee, Jong Seok; Ha, Hyun Kwon; Tirumani, Sree Harsha; Ramaiya, Nikhil H

    2015-01-01

    To comprehensively analyze the spectrum of imaging features of the primary tumors and metastatic patterns of the Extraskeletal Ewing sarcoma family of tumors (EES) in adults. We performed a computerized search of our hospital's data-warehouse from 1996 to 2013 using codes for Ewing sarcoma and primitive neuroectodermal tumors as well as the demographic code for ≥ 18 years of age. We selected subjects who were histologically confirmed to have Ewing sarcoma of extraskeletal origin. Imaging features of the primary tumor and metastatic disease were evaluated for lesion location, size, enhancement pattern, necrosis, margin, and invasion of adjacent organs. Among the 70 patients (mean age, 35.8 ± 15.6 years; range, 18-67 years) included in our study, primary tumors of EES occurred in the soft tissue and extremities (n = 20), abdomen and pelvis (n = 18), thorax (n = 14), paravertebral space (n = 8), head and neck (n = 6), and an unknown primary site (n = 4). Most primary tumors manifested as large and bulky soft-tissue masses (mean size, 9.0 cm; range, 1.3-23.0 cm), frequently invading adjacent organs (45.6%) and showed heterogeneous enhancement (73.7%), a well-defined (66.7%) margin, and partial necrosis/cystic degeneration (81.9%). Notably, 29 patients had metastatic disease detected at their initial diagnosis. The most frequent site of metastasis was lymph nodes (75.9%), followed by bone (31.0%), lung (20.7%), abdominal solid organs (13.8%), peritoneum (13.8%), pleura (6.9%), and brain (3.4%). Primary tumors of EES can occur anywhere and mostly manifest as large and bulky, soft-tissue masses. Lymph nodes are the most frequent metastasis sites.

  10. NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis.

    Science.gov (United States)

    Lai, Jin-Ping; Robbins, Paul F; Raffeld, Mark; Aung, Phyu Phyu; Tsokos, Maria; Rosenberg, Steven A; Miettinen, Markku M; Lee, Chyi-Chia Richard

    2012-06-01

    A promising targeted therapy against NY-ESO-1 (CTAG 1B) using genetically modified T-cells in synovial sarcomas was recently demonstrated in a clinical trial at the NCI. To investigate the role of NY-ESO-1 immunohistochemistry in patient selection and gain better insight into the incidence of NY-ESO-1 expression in synovial sarcomas and other mesenchymal tumors, we evaluated NY-ESO-1 expression by immunohistochemistry in 417 tumors. This collection of samples included: 50 SS18/SSX1/2 fusion positive synovial sarcomas, 155 gastrointestinal stromal tumors (GIST), 135 other spindle cell sarcomas as well as 77 other sarcomas (chondrosarcoma, osteosarcoma, dedifferentiated liposarcoma, alveolar soft part sarcoma, rhabdomyosarcoma, angiosarcoma, malignant mesothelioma, and Ewing's sarcoma). We report that 76% of synovial sarcomas expressed NY-ESO-1 in a strong and diffuse pattern (2-3+, >50-70% of tumor cells). In contrast, only rare cases of other spindle cell mesenchymal tumor expressed NY-ESO-1 (GIST (2/155), malignant peripheral nerve sheath tumors (1/34), and dermatofibrosarcoma protuberans (2/20)). Individual cases of other sarcomas (angiosarcoma, malignant mesothelioma, chondrosarcoma, osteosarcoma, dedifferentiated liposarcoma, alveolar soft part sarcoma, and Ewing's sarcoma) were positive for NY-ESO-1. However, no positive cases were identified amongst our cohort of leiomyosarcomas (0/24), hemangiopericytoma/solitary fibrous tumors (0/40), and cellular schwannomas (0/17). In summary, we find that NY-ESO-1 is strongly and diffusely expressed in a majority of synovial sarcomas, but only rarely in other mesenchymal lesions. Beyond its role in patient selection for targeted therapy, immunohistochemistry for NY-ESO-1 may be diagnostically useful for the distinction of synovial sarcoma from other spindle cell neoplasms.

  11. 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....

  12. Skin-nipple-sparing mastectomy: The first approach in primary myxoid chondrosarcoma of the breast

    Directory of Open Access Journals (Sweden)

    G. Militello

    2017-01-01

    Until 2013, the gold standard was the radical mastectomy. By 2014, there were two cases of conservative approach to quadrantectomy. To our knowledge, this represents the first case in the literature in which a skin-nipple-sparing mastectomy has been performed on a primitive mesenchymal neoplasm of the breast. Such an oncoplastic approach was performed considering the young age of the woman, to assure the surgical radicality and a better quality of life to the patient.

  13. Brachyury, SOX-9, and Podoplanin, New Markers in the Skull Base Chordoma Vs Chondrosarcoma Differential: A Tissue Microarray Based Comparative Analysis

    Science.gov (United States)

    Oakley, GJ; Fuhrer, K; Seethala, RR

    2014-01-01

    The distinction between chondrosarcoma and chordoma of the skull base/head and neck is prognostically important; however, both have sufficient morphologic overlap to make distinction difficult. As a result of gene expression studies, additional candidate markers have been proposed to help in this distinction. Hence, we sought to evaluate the performance of new markers: brachyury, SOX-9, and podoplanin alongside the more traditional markers glial fibrillary acid protein, carcinoembryonic antigen, CD24 and epithelial membrane antigen. Paraffin blocks from 103 skull base/head and neck chondroid tumors from 70 patients were retrieved (1969-2007). Diagnoses were made based on morphology and/or whole section immunohistochemistry for cytokeratin and S100 protein yielding 79 chordomas (comprising 45 chondroid chordomas and 34 conventional chordomas), and 24 chondrosarcomas. A tissue microarray containing 0.6 mm cores of each tumor in triplicate was constructed using a manual array (MTA-1, Beecher Instruments). For visualization of staining, the ImmPRESS detection system (Vector Laboratories) with 2 - diaminobenzidine substrate was used. Sensitivities and specificities were calculated for each marker. Core loss from the microarray ranged from 25-29% yielding 66-78 viable cases per stain. The classic marker, cytokeratin, still has the best performance characteristics. When combined with brachyury, accuracy improves slightly (sensitivity and specificity for detection of chordoma 98% and 100%, respectively). Positivity for both epithelial membrane antigen and AE1/AE3 had a sensitivity of 90% and a specificity of 100% for detecting chordoma in this study. SOX-9 is apparently common to both notochordal and cartilaginous differentiation, and is not useful in the chordoma-chondrosarcoma differential diagnosis. Glial fibrillary acid protein, carcinoembryonic antigen, CD24, and epithelial membrane antigen did not outperform other markers, and are less useful in the diagnosis of

  14. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

    International Nuclear Information System (INIS)

    Collins, Mark S.; Koyama, Takashi; Swee, Ronald G.; Inwards, Carrie Y.

    2003-01-01

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  15. Osteossarcoma extra-esquelético primário da região frontal Extraskeletal primary osteosarcoma of the frontal region

    Directory of Open Access Journals (Sweden)

    M.A. Lima

    1998-03-01

    Full Text Available OBJETIVO: Osteossarcoma extra-esquelético (OSEE primário de partes moles da cabeça é raro e não há, ao que nos parece, relato dele originando na região frontal. MÉTODOS: Homem de 78 anos, italiano, com história de tumoração em partes moles de região frontal há um mês. Tomografia computadorizada mostrou massa de densidade irregular ocupando tecido celular subcutâneo e fáscia. Nenhum tumor ósseo foi encontrado. A tumoração foi completamente ressecada, media 0,8x0,6x0,5cm, e a superfície de corte era sólida. Diagnosticou-se osteossarcoma osteoblástico extra-esquelético. A neoplasia recorreu quatro meses após o diagnóstico e foi novamente ressecado. O paciente foi submetido também a radioterapia de baixa penetração, e nove meses depois da primeira biópsia tinha sintomas em decorrência da infiltração neoplásica na base do crânio. O óbito ocorreu dez meses após a primeira biópsia. CONCLUSÃO: Os autores descrevem o primeiro caso de OSEE da região frontal sem uma condição preexistente ou história de irradiação.BACKGROUND: Extraskeletal osteosarcoma (ESOS in the head as a primary site has seldom been re-ported and none in the frontal region. METHODS: A 78-year-old Italian man presented with one month history of a frontal soft tissue mass. A CT scan showed a mass of uneven density occupying the subcutaneous soft tissue and involving fascial planes. No primary bone tumor was found. The entire mass was excised. The mass was solid measuring 0.8 x 0.6 x 0.5cm. Extraskeletal osteoblastic osteosarcoma was diagnosed by ligh microscopy. The tumor recurred four months after the diagnosis. The tumor was again ressected. The patient was also submitted to low penetration radiation therapy. Nine months after the first biopsy the patient had symptoms due to infiltration to the base of the cranium. He died 10 months after the first biopsy. CONCLUSIONS: The first case with ESOS of the frontal region without a pre

  16. Laryngeal chondrosarcoma mimicking medullary thyroid carcinoma on fine-needle aspiration cytology: A case report of a diagnostic pitfall.

    Science.gov (United States)

    Vahidi, Shifteh; Amin, Khalid; Stewart, Jimmie

    2017-11-01

    Chondrosarcoma (CS) of larynx is a rare laryngeal tumor accounting about 1% of laryngeal malignancies. When CS arises from thyroid cartilage, it may clinically present as a thyroid nodule. Here we report a rare case of CS of thyroid cartilage misinterpreted as medullary thyroid carcinoma. The main aim of this case report is to emphasize the important role of accurate clinical history, appropriate physical examination, and proper localization of the tumor and clear definitive imaging in conjunction with interpretation of cytologic smears. When any of these roles are unclear, it may result in misinterpretation of the cytologic smears. In these unusual circumstances, when cytomorphologic features does not completely fit an entity, communication with the physician and the consideration of a broad differential diagnoses in the head and neck pathology may lead to correct diagnosis and avoid diagnostic pitfalls. Also in certain conditions, ancillary studies including laboratory tests are necessary for definitive classification. © 2017 Wiley Periodicals, Inc.

  17. Mesenchymal hamartoma of the liver

    International Nuclear Information System (INIS)

    Sohn, Cheul Ho; Woo, Seong Ku; Park, Woo Hyun; Choi, Soon Ok

    1990-01-01

    Mesenchymal hamartoma of the liver is a relatively uncommon lesion that occurs with greatest frequency under 2 years of age. Authors experienced a case of giant mesenchymal hamartoma of the liver in a 7-month-old boy. Ultrasonography and computed tomography reveal a large, predominantly cystic mass with thick internal septa

  18. 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...

  19. Targeted next-generation sequencing of dedifferentiated chondrosarcoma in the skull base reveals combined TP53 and PTEN mutations with increased proliferation index, an implication for pathogenesis

    OpenAIRE

    Gao, Lu; Hong, Xiafei; Guo, Xiaopeng; Cao, Dengfeng; Gao, Xiaohuan; DeLaney, Thomas F.; Gong, Xinqi; Chen, Rongrong; Ni, Jianjiao; Yao, Yong; Wang, Renzhi; Chen, Xi; Tian, Pangzehuan; Xing, Bing

    2016-01-01

    Dedifferentiated chondrosarcoma (DDCS) is a rare disease with a dismal prognosis. DDCS consists of two morphologically distinct components: the cartilaginous and noncartilaginous components. Whether the two components originate from the same progenitor cells has been controversial. Recurrent DDCS commonly displays increased proliferation compared with the primary tumor. However, there is no conclusive explanation for this mechanism. In this paper, we present two DDCSs in the sellar region. Pa...

  20. Condrossarcoma laríngeo: relato de caso e revisão de literatura Laryngeal chondrosarcoma: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Giordania Gomes Campos

    2004-12-01

    Full Text Available Os tumores cartilaginosos da laringe são extremamente raros e correspondem a aproximadamente 1% dos tumores que acometem este órgão. Menos que 0,1% destes tumores correspondem aos condrossarcomas. Os condromas e os condrossarcomas de baixo grau são os mais freqüentemente encontrados e 70-75% destes tumores localizam-se na face laríngea da lâmina posterior da cartilagem cricóidea. O diagnóstico do condrossarcoma da laringe pode ser esquecido devido a sua baixa ocorrência e sua forma indolente de crescimento. A apresentação clínica é variada e diretamente dependente do tamanho e localização do tumor: estridor, cornagem, dispnéia, disfagia ou massa cervical são os sinais mais freqüentes. O objetivo deste estudo é apresentar um caso incomum de condrossarcoma laríngeo de origem na cartilagem tireóidea, discutindo o quadro clínico, o diagnóstico, tratamento e os fatores prognósticos.Cartilaginous tumors of the larynx are extremely rare neoplasms that account for approximately one per cent of all tumors of this organ. Less than 0.1% correspond to chondrosarcomas. Chondroma and low-grade chondrosarcoma are the most common, 70-75% of these tumors arise on the endolaryngeal surface of the posterior lamina of the cricoid cartilage. The diagnosis of laryngeal chondrosarcoma is likely to be missed because of its infrequent occurrence and its indolent pattern of growth. The clinical presentation is varied and directly dependent on size and location of tumor: stridor, hoarseness, dyspnea or neck mass are commonly presented signs. The objective of this study was to show an unusual case of laryngeal chondrosarcoma originating from thyroid cartilage, discussing its clinical presentation, diagnosis, treatment and prognosis.

  1. Creation of false pedicles and a neo-pelvis for lumbopelvic reconstruction following en bloc resection of an iliosacral chondrosarcoma with lumbar spine extension: technical note.

    Science.gov (United States)

    Mendel, Ehud; Nathoo, Narendra; Scharschmidt, Thomas; Schmidt, Carl; Boehmler, James; Mayerson, Joel L

    2014-03-01

    En bloc resection with negative tumor margins remains the principal treatment option for control or cure of primary pelvic chondrosarcomas, as current adjuvant therapies remain ineffective. Iliosacral chondrosarcomas with involvement of the sciatic notch are sufficiently challenging tumors. However, when there is concomitant lumbar extension requiring resection of the pedicles to maintain negative surgical margins, transpedicular screw fixation is not possible, making reconstruction of the lumbopelvic junction extremely challenging. A patient with an iliosacral chondrosarcoma with lumbar spine extension is presented in this report to illustrate a novel lumbopelvic spinal construct. Following combined external pelvectomy and hemisacrectomy with contralateral L3-5 hemilaminectomy and ipsilateral pediculotomy, bicortical transvertebral body screws were substituted for the missing pedicles, resulting in the creation of "false pedicles," which were further supplemented with an autologous vascularized fibular strut graft from the amputated lower limb and applied to the lateral aspect of the vertebral bodies. The creation of false pedicles allowed for a robust reconstruction of the lumbopelvic junction, including maintaining pelvic ring integrity with a "neo-pelvis", creating a functional load-bearing construct adequate for early mobilization and ambulation. The biomechanical dynamics of this unique construct are also discussed.

  2. [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.

  3. Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......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...... 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...

  4. Mesenchymal Cells in Colon Cancer.

    Science.gov (United States)

    Koliaraki, Vasiliki; Pallangyo, Charles K; Greten, Florian R; Kollias, George

    2017-04-01

    Mesenchymal cells in the intestine comprise a variety of cell types of diverse origins, functions, and molecular markers. They provide mechanical and structural support and have important functions during intestinal organogenesis, morphogenesis, and homeostasis. Recent studies of the human transcriptome have revealed their importance in the development of colorectal cancer, and studies from animal models have provided evidence for their roles in the pathogenesis of colitis-associated cancer and sporadic colorectal cancer. Mesenchymal cells in tumors, called cancer-associated fibroblasts, arise via activation of resident mesenchymal cell populations and the recruitment of bone marrow-derived mesenchymal stem cells and fibrocytes. Cancer-associated fibroblasts have a variety of activities that promote colon tumor development and progression; these include regulation of intestinal inflammation, epithelial proliferation, stem cell maintenance, angiogenesis, extracellular matrix remodeling, and metastasis. We review the intestinal mesenchymal cell-specific pathways that regulate these processes, with a focus on their roles in mediating interactions between inflammation and carcinogenesis. We also discuss how increasing our understanding of intestinal mesenchymal cell biology and function could lead to new strategies to identify and treat colitis-associated cancers. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Radiation-induced chondrosarcoma of the scapula after radiotherapy for lung cancer: a case report and review of the literature.

    Science.gov (United States)

    Zidane, Abdelfettah; Arsalane, Adil; Lahkim, Mohammed; Lalya, Issam; Ktaibi, Abderrahim; Essadi, Ismail

    2018-03-05

    Radiotherapy associated with chemotherapy is a well-established treatment modality for locally advanced non-small cell lung cancers. Radiation-induced second malignancies, particularly radiation-induced sarcomas, are rare. Some authors reported a recent increase in the incidence of this rare complication, especially because of the improved prognosis and survival of patients after radiotherapy. Pathogenic mechanisms of radiation-induced sarcomas are poorly understood. However, diagnosis criteria are well established. Treatment options must be discussed and adapted to the patient's profile. Surgery in irradiated tissue is challenging, with limited treatment options with chemotherapy and radiotherapy. We report the case of a 62-year-old Moroccan man diagnosed as having chondrosarcoma of his right scapula, who was irradiated 10 years ago for stage IIIB non-small cell lung cancer. This case was managed by a complete resection of the tumor with good functional and oncological outcomes. To the best of our knowledge, the scapular location of radiation-induced sarcoma after irradiation for lung cancer has never been described in the literature. Radiation-induced sarcoma of the scapula represents a rare situation that must be actively researched to have access to an optimal therapeutic approach.

  6. Celastrol inhibits chondrosarcoma proliferation, migration and invasion through suppression CIP2A/c-MYC signaling pathway

    Directory of Open Access Journals (Sweden)

    Jinhui Wu

    2017-05-01

    Full Text Available Chondrosarcomas (CS is the second most frequent tumors of cartilage origin. A small compound extracted from Thunder God Vine (Tripterygium wilfordii Hook. F. called celastrol can directly bound CIP2A protein and effectively inhibit cell proliferation and induce apoptosis in several cancer cells. However, little knowledge is concern about the important role of CIP2A in CS patients and the therapeutic value of celastrol on CS. Our results showed that CIP2A and c-MYC were verified to be oncoproteins by detecting their mRNA and protein expression in 10 human CS tissues by qRT-PCR and Western blots. After treatment of celastrol, the proliferation, migration and invasion were significantly inhibited; whereas the apoptosis was largely induced in human CS cell lines. In addition, celastrol inhibited the expression of CIP2A, c-MYC, and suppressed apoptotic proteins BAX and caspase-8 in human CS cells, on the other hand, it induced the expression of antiapoptotic protein Bcl-2. Finally, knockdown of CIP2A also inhibited the migration and invasion and induced apoptosis of human CS cells. To sum up, we found that celastrol had effects on inhibiting proliferation, migration, invasion and inducing apoptosis through suppression CIP2A/c-MYC signaling pathway in vitro, which may provide a new therapeutic regimen for CS.

  7. Are mesenchymal stromal cells immune cells?

    NARCIS (Netherlands)

    M.J. Hoogduijn (Martin)

    2015-01-01

    textabstractMesenchymal stromal cells (MSCs) are considered to be promising agents for the treatment of immunological disease. Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities.

  8. Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study

    Energy Technology Data Exchange (ETDEWEB)

    Feuvret, Loïc, E-mail: loic.feuvret@psl.aphp.fr [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bracci, Stefano [Institute of Radiation Oncology, Sapienza University, Sant' Andrea Hospital, Rome (Italy); Calugaru, Valentin [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bolle, Stéphanie [Department of Radiation Oncology, Gustave Roussy, Villejuif (France); Mammar, Hamid; De Marzi, Ludovic [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bresson, Damien [Department of Neurosurgery, Hôpital Lariboisière (Assistance Publique–Hôpitaux de Paris), Paris (France); Habrand, Jean-Louis [Department of Radiation Oncology, Centre François Baclesse, Caen (France); Mazeron, Jean-Jacques [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Dendale, Rémi [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); and others

    2016-05-01

    Purpose: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). Methods and Materials: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. Results: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Conclusions: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.

  9. Extraskeletal Effects of Vitamin D

    Directory of Open Access Journals (Sweden)

    V.V. Povoroznyuk

    2014-02-01

    Thus, the condition of deficiency or a failure of VD gains the predictor importance of a wide range of pathological states development, and also promotes increase in indexes both of total mortality and lethality from cardiovascular pathology, oncopathology and respiratory organs diseases.

  10. Conditional mesenchymal disruption of pkd1 results in osteopenia and polycystic kidney disease.

    Directory of Open Access Journals (Sweden)

    Ni Qiu

    Full Text Available Conditional deletion of Pkd1 in osteoblasts using either Osteocalcin(Oc-Cre or Dmp1-Cre results in defective osteoblast-mediated postnatal bone formation and osteopenia. Pkd1 is also expressed in undifferentiated mesenchyme that gives rise to the osteoblast lineage. To examine the effects of Pkd1 on prenatal osteoblast development, we crossed Pkd1(flox/flox and Col1a1(3.6-Cre mice, which has been used to achieve selective inactivation of Pkd1 earlier in the osteoblast lineage. Control Pkd1(flox/flox and Pkd1(flox/+, heterozygous Col1a1(3.6-Cre;Pkd1(flox/+ and Pkd1(flox/null, and homozygous Col1a1(3.6-Cre;Pkd1(flox/flox and Col1a1(3.6-Cre;Pkd1(flox/null mice were analyzed at ages ranging from E14.5 to 8-weeks-old. Newborn Col1a1(3.6-Cre;Pkd1(flox/null mice exhibited defective skeletogenesis in association with a greater reduction in Pkd1 expression in bone. Conditional Col1a1(3.6-Cre;Pkd1(flox/+ and Col1a1(3.6-Cre;Pkd1(flox/flox mice displayed a gene dose-dependent decrease in bone formation and increase in marrow fat at 6 weeks of age. Bone marrow stromal cell and primary osteoblast cultures from homozygous Col1a1(3.6-Cre;Pkd1(flox/flox mice showed increased proliferation, impaired osteoblast development and enhanced adipogenesis ex vivo. Unexpectedly, we found evidence for Col1a1(3.6-Cre mediated deletion of Pkd1 in extraskeletal tissues in Col1a1(3.6-Cre;Pkd1(flox/flox mice. Deletion of Pkd1 in mesenchymal precursors resulted in pancreatic and renal, but not hepatic, cyst formation. The non-lethality of Col1a1(3.6-Cre;Pkd1(flox/flox mice establishes a new model to study abnormalities in bone development and cyst formation in pancreas and kidney caused by Pkd1 gene inactivation.

  11. Osteossarcoma extra-esquelético na região cervical: revisão da literatura e relato de caso clínico Extraskeletal osteosarcoma in the neck: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    José Jorge Gomes Lima

    2002-10-01

    Full Text Available O osteossarcoma extra-esquelético é uma neoplasia rara caracterizada pela produção de osteóide "maligno". Esta condição tem sido descrita em faixa etária acima da esperada para o osteossarcoma ósseo, e a coxa é o local de predileção. Realizamos revisão da literatura e descrevemos o caso clínico de uma paciente de 19 anos de idade com história de massa na região cervical direita associada a parestesia dos membros superiores, a qual foi diagnosticada como portadora de osteossarcoma extra-esquelético. Enfatizamos as características clínicas, os aspectos das imagens em diversos métodos empregados (exames radiográficos convencionais, tomografia computadorizada, exame por ressonância magnética, análise histopatológica e os principais diagnósticos diferenciais desta afecção.Extraskeletal osteosarcoma is a rare neoplasm characterized by the formation of a malignant osteoid. This condition is usually described in patients aged greater than expected for other intraosseous osteosarcomas, and the thigh is the most common site. We report a clinical case of a 19-year-old female patient and review the literature. The patient presented with a mass in the right side of the neck and paresthesia of the upper limbs. The mass corresponded to an extraskeletal osteosarcoma. We discuss the clinical findings, image findings (conventional radiographs, computed tomography, magnetic resonance imaging, histopathology results and differential diagnosis of this condition.

  12. Mesenchymal hamartoma of the liver.

    Science.gov (United States)

    Gupta, Rahul; Parelkar, Sandesh V; Sanghvi, Beejal

    2009-10-01

    Mesenchymal hamartoma of the liver is the second most common benign liver tumor in children, yet its biology and pathogenesis are poorly understood. Typically, it presents as a large benign multicystic liver mass in children younger than three years, amenable to complete resection. Most tumors gradually increase in size, some reaching enormous proportions, some can undergo incomplete spontaneous regression, and rarely, few have shown malignant transformation to undifferentiated (embryonal) sarcoma. Here, we report a 13 month-old child who presented with abdominal distension and respiratory distress. Ultrasonography, Computed Tomography (CT), and magnetic resonance imaging (MRI) of the abdomen were suggestive of a mesenchymal hamartoma of the liver. Right hepatectomy was performed. Postoperatively, the patient recovered well. An attempt was also made to understand the possible etiology of the tumor.

  13. The pulmonary mesenchyme directs lung development.

    Science.gov (United States)

    McCulley, David; Wienhold, Mark; Sun, Xin

    2015-06-01

    Each of the steps of respiratory system development relies on intricate interactions and coordinated development of the lung epithelium and mesenchyme. In the past, more attention has been paid to the epithelium than the mesenchyme. The mesenchyme is a source of specification and morphogenetic signals as well as a host of surprisingly complex cell lineages that are crucial for normal lung development and function. This review highlights recent research focusing on the mesenchyme that has revealed genetic and epigenetic mechanisms of its development in the context of other cell layers during respiratory lineage specification, branching morphogenesis, epithelial differentiation, lineage distinction, vascular development, and alveolar maturation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

    Science.gov (United States)

    Landsman, Limor; Nijagal, Amar; Whitchurch, Theresa J; Vanderlaan, Renee L; Zimmer, Warren E; Mackenzie, Tippi C; Hebrok, Matthias

    2011-09-01

    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 essential mediator

  15. 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

  16. Hemipelvectomia no tratamento de condrossarcoma no acetábulo de cão Hemipelvectomy in the treatment of chondrosarcoma of the acetabulum dog

    Directory of Open Access Journals (Sweden)

    Daniel Curvello de Mendonça Müller

    2010-05-01

    Full Text Available Hemipelvectomia é a remoção de parte da pelve e tem sido indicada no tratamento cirúrgico de tumores malignos. Este estudo apresenta o caso de um paciente canino, portador de condrossarcoma recidivante, submetido à hemipelvectomia parcial com amputação do membro. O objetivo deste trabalho é ressaltar a importância da cirurgia radical no tratamento de condrossarcoma ósseo, abordando uma alternativa viável e pouco convencional para pacientes acometidos por tumores na pelve, que frente à extensão da lesão podem ser erroneamente diagnosticados como portadores de neoplasias não tratáveis. Após a realização da hemipelvectomia parcial com amputação do membro, o animal obteve retorno satisfatório à deambulação, sem dificuldade de apoio ou alteração de equilíbrio.Hemipelvectomy is the removal of part of the pelvis and is indicated for the surgical treatment of malignant tumors. This study presents the case of a canine patient with recurrent chondrosarcoma, submitted to hemipelvectomy with limb amputation. The report aims to highlight the importance of surgery in the treatment of radial bone chondrosarcoma, addressing a viable and unconventional alternative for patients suffering from tumors in the pelvis, which against the extension of the lesion may be misdiagnosed as intractable cancer. After the partial hemipelvectomy with amputation of the limb the animal satisfactory returned to ambulation without difficulty in supporting or alteration in balance.

  17. Surgical treatment is decisive for outcome in chondrosarcoma of the chest wall: a population-based Scandinavian Sarcoma Group study of 106 patients.

    Science.gov (United States)

    Widhe, Björn; Bauer, Henrik C F

    2009-03-01

    Chondrosarcoma of the chest wall is the most frequent primary malignant chest wall tumor. Surgery remains the only effective treatment. Sarcoma treatment in Sweden is centralized to sarcoma centers; however, sarcomas of the chest wall have also been handled by thoracic and general surgeons. One hundred six consecutive reports of chondrosarcomas of the rib and sternum over a 22-year period (1980 to 2002) were studied, with a median of 9 (4 to 23) years of follow-up for survivors. Clinical files were gathered and pathologic specimens reviewed and graded 1 to 4 by the Scandinavian sarcoma pathology group. Surgical margins were defined as wide, marginal, or intralesional. Ninety-seven patients were treated with a curative intent. Patients operated with wide surgical margins had a 10-year survival of 92% compared with 47% for those with intralesional resections. The 10-year survival was 75% for patients treated at sarcoma centers and 59% for those treated by thoracic or general surgeons. Local recurrence rate was highly dependent of the surgical margins-4% after wide resections and 73% after intralesional resections. The proportion of intralesional resections was higher outside sarcoma centers. Prognostic factors (multivariate analysis) for local recurrence included surgical margin and histological grade; for metastases, prognostic factors included histologic grade, tumor size, and local recurrence. Metastases occurred in 21 of the patients and only 2 were cured. Patients operated with wide surgical margins resulted in fewer local recurrences and better overall survival. Patients with chest wall tumors should be referred to sarcoma centers and not to general thoracic surgery clinics for diagnosis and treatment.

  18. 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...

  19. The role of the adaptive immune system in burn-induced heterotopic ossification and mesenchymal cell osteogenic differentiation.

    Science.gov (United States)

    Ranganathan, Kavitha; Agarwal, Shailesh; Cholok, David; Loder, Shawn; Li, Jonathan; Sung Hsieh, Hsiao Hsin; Wang, Stewart C; Buchman, Steven R; Levi, Benjamin

    2016-11-01

    Heterotopic ossification (HO) is the pathologic process of extraskeletal bone formation. Although the exact etiology remains unknown, inflammation appears to catalyze disease progression. The goal of this study is to determine the impact of the adaptive immune system on HO. HO was induced in 8-wk-old control C57BL/6 and immunocompromised Rag1tm1Mom (Rag1 KO) male mice deficient in B- and T-lymphocytes via combined Achilles tenotomy and burn injury. Microcomputed tomography quantified the extent of HO formation at the tenotomy site. Adipose-derived mesenchymal stem cells were harvested to evaluate osteogenic differentiation potential. Areas of developing HO demonstrated substantial enrichment of CD45 + leukocytes at 3 wk after injury. HO from Rag1 KO mice was substantially less mature with foci of cartilage and disorganized trabecular bone present 12 wk after injury. Rag1 KO mice formed 60% less bone compared to immunocompetent controls (4.67 ± 1.5 mm versus 7.76 ± 0.65 mm; P = 0.001). Tartrate-resistant acid phosphatase staining and immunofluorescent analysis of osteoprotegerin and nuclear factor kappa-light-chain-enhancer of activated B cells demonstrated no appreciable difference in osteoclast number or activation. Alizarin red staining in vitro demonstrated a significant decrease in osteogenic potential in immunocompromised mice compared to controls (29.1 ± 0.54 mm versus 12.1 ± 0.14 mm; P role for the adaptive immune system in the development of HO. In the absence of mature B- and T-lymphocytes, HO growth and development are attenuated. Furthermore, we demonstrate that mesenchymal populations from B- and T-cell deficient mice are inherently less osteogenic. This study identifies a potential therapeutic role for modulation of the adaptive immune system in the treatment of HO. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Mesenchymal stem cells in regenerative rehabilitation.

    Science.gov (United States)

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-06-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient's medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future.

  1. Mesenchymal stem cells avoid allogeneic rejection

    Directory of Open Access Journals (Sweden)

    Murphy J Mary

    2005-07-01

    Full Text Available Abstract Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

  2. Suppression of chondrosarcoma cells by 15-deoxy-Δ12,14-prostaglandin J2 is associated with altered expression of Bax/Bcl-xL and p21

    International Nuclear Information System (INIS)

    Shen, Zheng-Nan; Nishida, Keiichiro; Doi, Hideyuki; Oohashi, Toshitaka; Hirohata, Satoshi; Ozaki, Toshifumi; Yoshida, Aki; Ninomiya, Yoshifumi; Inoue, Hajime

    2005-01-01

    We previously reported that 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), the most potent agonist for peroxisome proliferator-activated receptor γ (PPARγ), induces apoptosis of human chondrosarcoma cell line OUMS-27. The current study aimed to explore the mechanism of 15d-PGJ 2 -induced apoptosis and inhibition of cell proliferation in OUMS-27 cells. The preliminary results of cDNA microarray analysis showed the down-regulation of anti-apoptotic Bcl-xL and up-regulation of pro-apoptotic Bax in the process of 15d-PGJ 2 -induced apoptosis. These changes were further confirmed at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ 2 , but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation. Activation of caspase-3 by 15d-PGJ 2 was partly, but not completely, blocked by PPARγ antagonist (GW9662) suggesting the 15d-PGJ 2 exerted its effect by PPARγ-dependent and -independent pathways. Interestingly, immunohistochemical study on human chondrosarcoma samples revealed that Bcl-xL is frequently expressed by tumor cells. The results of the current study suggest that the potential ability of 15d-PGJ 2 in regulation of cell cycle and inhibition of Bcl-xL expression might be beneficial in the development of novel pharmacological agents for chondrosarcoma

  3. Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit), and YKL-40

    Science.gov (United States)

    DAUGAARD, SØREN; CHRISTENSEN, LISE H; HØGDALL, ESTRID

    2009-01-01

    Chondroid tumors comprise a heterogenous group of benign to overt malignant neoplasms, which may be difficult to differentiate from one another by histological examination. A group of 43 such tumors was stained with nine relevant antibodies in an attempt to find consistent marker profile(s) for the different subgroups. Archival material from three extraskeletal myxoid chondrosarcomas, five chordomas, five chondromyxoid fibromas, five chondroblastomas and 25 chondrosarcomas was stained with antibodies against osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit) and YKL-40. All 25 chondrosarcomas showed a positive staining reaction for D2-40, none for actin and CD117, and a partial reactivity for bcl-2 (36%). Chondroblastomas (5/5) and chondromyxoid fibromas (2/5) were the only tumors with a positive reaction for actin, and all chondroblastomas (n=5) and extraskeletal myxoid chondrosarcomas (n=3) were positive for bcl-2. In contrast to all other tumors, two of three extraskeletal myxoid chondrosarcomas were also positive for CD17 and negative for osteonectin, cox-2, mdm-2 and actin. All five chordomas were negative for D2-40 and positive for mdm-2 and YKL-40. The diagnosis of chondrosarcoma may be aided by its positivity for D2-40 and YKL-40 and its lack of reactivity for actin and CD117. This should be seen in the light of no reaction for D2-40 in chordomas and a corresponding lack of reaction for osteonectin, cox-2, mdm-2 and actin in extraskeletal myxoid chondrosarcomas. A convincing immunoreactivity for calponin and/or actin in chondromyxoid fibromas and chondroblastomas may also be helpful in differentiating these tumors from chondrosarcomas. PMID:19594492

  4. Andrographolide suppresses epithelial mesenchymal transition by ...

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... Subsequently these EMT-induced cells were treated with andrographolide at 100 and 500 nM concentrations for 24 h. ...... Radisky DC and LaBarge MA 2008 Epithelial-mesenchymal tran- sition and the stem cell phenotype. Cell Stem Cell. 2 511–512. Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C ...

  5. Cryopreservation and revival of mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Haack-Sørensen, Mandana; Kastrup, Jens

    2011-01-01

    initiated. As there has been a precedent for the use of bone marrow stem cells in the treatment of hematological malignancies and ischemic heart diseases through randomized clinical safety and efficacy trials, the development of new therapies based on culture-expanded human mesenchymal stromal cells (MSCs...

  6. Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity

    NARCIS (Netherlands)

    Luk, Franka; de Witte, Samantha F. H.; Korevaar, Sander S.; Roemeling, Marieke; Franquesa, Marcella; Strini, Tanja; van den Engel, Sandra; Gargesha, Madhusudhana; Roy, Debashish; Dor, Frank J. M. F.; Horwitz, Edwin M.; de Bruin, Ron W. F.; Betjes, Michiel G. H.; Baan, Carla C.; Hoogduijn, Martin J.

    2016-01-01

    Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of

  7. 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.

  8. Chondrosarcoma of the femur with histology-imaging correlation of tumor growth--preliminary observations concerning periosteal new bone formation and soft tissue extension.

    Science.gov (United States)

    Steiner, German C; Schweitzer, Mark E; Kenan, Samuel; Abdelwahab, Ibrahim F

    2011-01-01

    The objective of this study was, in chondrosarcoma (CHS) of the femur, to evaluate by radiologic-pathologic correlation, the degree of tumor growth, cortical destruction, periosteal reaction, and soft tissue extension present. Eight cases of histologically proven CHS of the femur were studied. All cases were resected, evaluated histologically with coronal slabs, and compared with radiographs and magnetic resonance imaging (MRI) scans. In two resected specimens, the tumors were studied in more detail; along with coronal slabs, axial sections of the remaining anterior and posterior halves of both tumors were taken, and the bone specimens were X-rayed and examined histologically. CHS initially involved the medullary cavity and subsequently destroyed the cortex; first, by endosteal scalloping and, second, by subsequent invasion and destruction of the cortex. During this process, there was periosteal new bone formation (PNBF), with increased cortical thickness, the degree of which often correlated with the degree of cortical destruction. In the areas of cortical thickening of three cases, a "grey line" was seen on MRI that separated the cortex from the periosteal new bone; the line, in reality,is a space between the two structures. The presence of this line suggests that the tumor does not extend beyond the cortex. PNBF occurred in all cases and varied in thickness. It frequently developed independent of direct periosteal tumor involvement. The periosteum of one case contained porotic bone with interposed marrow fat, which was easily misinterpreted as tumor extension on MRI. Expansion and remodeling of the femoral diaphysis in CHS, with widening of the medullary cavity, is usually due to extensive cortical destruction with PNBF. Soft tissue extension was present in five cases and apparently occurred by two different mechanisms: direct tumor destruction of the cortex and periosteum, with extension into the soft tissues; and subtle MRI occult tumor permeation through the

  9. Mesenchymal change and drug resistance in neuroblastoma.

    Science.gov (United States)

    Naiditch, Jessica A; Jie, Chunfa; Lautz, Timothy B; Yu, Songtao; Clark, Sandra; Voronov, Dimitry; Chu, Fei; Madonna, Mary Beth

    2015-01-01

    Metastatic initiation has many phenotypic similarities to epithelial-to-mesenchymal transition, including loss of cell-cell adhesion, increased invasiveness, and increased cell mobility. We have previously demonstrated that drug resistance is associated with a metastatic phenotype in neuroblastoma (NB). The purpose of this project was to determine if the development of doxorubicin resistance is associated with characteristics of mesenchymal change in human NB cells. Total RNA was isolated from wild type (WT) and doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and analyzed using the Illumina Human HT-12 version 4 Expression BeadChip. Differentially expressed genes (DEGs) were identified. Volcano plots and heat maps were generated. Genes of interest with a fold change in expression >1.5 and an adjusted P change via multiple pathways in the transition to a drug-resistant state. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Mesenchymal stromal cells: misconceptions and evolving concepts.

    Science.gov (United States)

    Phinney, Donald G; Sensebé, Luc

    2013-02-01

    Nearly half a century has passed since the publication of the first articles describing plastic-adherent cells from bone marrow, referred to initially as colony-forming unit fibroblasts, then marrow stromal cells, mesenchymal stem cells and most recently multipotent mesenchymal stromal cells (MSCs). As expected, our understanding of the nature and biologic functions of MSCs has undergone major paradigm shifts over this time. Despite significant advances made in deciphering their complex biology and therapeutic potential in both experimental animal models and human clinical trials, numerous misconceptions regarding the nature and function of MSCs have persisted in the field. Continued propagation of these misconceptions in some cases may significantly impede the advancement of MSC-based therapies in clinical medicine. We have identified six prevalent misconceptions about MSCs that we believe affect the field, and we attempt to rectify them based on current available data. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  11. The role of the mesenchyme in cranial neural fold elevation

    Energy Technology Data Exchange (ETDEWEB)

    Morris-Wiman, J.A.

    1988-01-01

    It has been previously postulated that the expansion of an hyaluronate-rich extracellular matrix in the fold mesenchyme is responsible for neural fold elevation. In this study we provide evidence that such expansions may play an important role in cranial neural fold elevation by pushing the folds towards the dorsal midline to assist in their elevation. For mesenchymal expansion to result in fold elevation, hyaluronate (HA) and mesenchymal cells must be non-randomly distributed within the mesenchyme. Patterns of mesenchymal cell distribution and cell proliferation were analyzed using the computer-assisted method of smoothed spatial averaging. The distribution of Alcian blue-stained and {sup 3}H-glucosamine-labelled HA was also analyzed during cranial neural fold elevation using established image processing techniques. Analysis of the distribution of {sup 3}H-thymidine-labelled mesenchymal cells indicated that differential mitotic activity was not responsible for decreased mesenchymal cell density. Likewise, analysis of distribution patterns of {sup 3}H-glucosamine-labelled HA indicated that decreased HA concentration was not produced by regional differences in HA synthesis. These results suggest that decreases in mesenchymal cell density and HA concentration that occur during neural fold elevation are produced by mesenchymal expansion.

  12. Restoring physiological cell heterogeneity in the mesenchyme during tooth engineering.

    Science.gov (United States)

    Keller, Laetitia-Véronique; Kuchler-Bopp, Sabine; Lesot, Hervé

    2012-01-01

    Tooth development is controlled by reciprocal epithelial-mesenchymal interactions. Complete teeth can form when culturing and implanting re-associations between single embryonic dental epithelial and mesenchymal cells. Although epithelial histogenesis is clear, very little is known about cell diversity and patterning in the mesenchyme. The aim of this work was to compare the situation in engineered and developing teeth at similar developmental stages. To this end, the expression of cell surface markers in the mesenchyme was investigated by immunostaining in: 1) embryonic mouse molars at embryonic day 14, as the initial cell source for re-associations, 2) cultured cell re-associations just before their implantation and 3) cultured cell re-associations implanted for two weeks. Surface markers allowed visualization of the complex patterning of different cell types and the differential timing in their appearance. The phenotype of mesenchymal cells rapidly changed when they were grown as a monolayer, even without passage. This might explain the rapid loss of their potential to sustain tooth formation after re-association. Except for markers associated with vascularization, which is not maintained in vitro, the staining pattern in the mesenchyme of cultured re-associations was similar to that observed in situ. After implantation, vascularization and the cellular heterogeneity in the mesenchyme were similar to what was observed in developing molars. Besides tissue oxygenation and its role in mineralization of dental matrices, vascularization is involved in the progressive increase in mesenchymal cell heterogeneity, by allowing external cells to enter the mesenchyme.

  13. The role of the mesenchyme in cranial neural fold elevation

    International Nuclear Information System (INIS)

    Morris-Wiman, J.A.

    1988-01-01

    It has been previously postulated that the expansion of an hyaluronate-rich extracellular matrix in the fold mesenchyme is responsible for neural fold elevation. In this study we provide evidence that such expansions may play an important role in cranial neural fold elevation by pushing the folds towards the dorsal midline to assist in their elevation. For mesenchymal expansion to result in fold elevation, hyaluronate (HA) and mesenchymal cells must be non-randomly distributed within the mesenchyme. Patterns of mesenchymal cell distribution and cell proliferation were analyzed using the computer-assisted method of smoothed spatial averaging. The distribution of Alcian blue-stained and 3 H-glucosamine-labelled HA was also analyzed during cranial neural fold elevation using established image processing techniques. Analysis of the distribution of 3 H-thymidine-labelled mesenchymal cells indicated that differential mitotic activity was not responsible for decreased mesenchymal cell density. Likewise, analysis of distribution patterns of 3 H-glucosamine-labelled HA indicated that decreased HA concentration was not produced by regional differences in HA synthesis. These results suggest that decreases in mesenchymal cell density and HA concentration that occur during neural fold elevation are produced by mesenchymal expansion

  14. Mesenchymal stem cells induce dermal fibroblast responses to injury

    International Nuclear Information System (INIS)

    Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

    2010-01-01

    Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

  15. Mesenchymal neoplasia and congenital pulmonary cysts

    International Nuclear Information System (INIS)

    Weinberg, A.G.; Currarino, G.; Moore, G.C.; Votteler, T.P.

    1980-01-01

    A malignant mesenchymoma exibiting a varied spectrum of differentation developed within a congenital pulmonary cyst 6 1/2 years after the cyst was first recognized. Related tumors with a similar gross appearance have been previously described and have included rhabdomyosarcomas and so-called pulmonary blastomas. There is a low but distinct risk for the developement of mesenchymal sarcomas within congenital peripheral pulmonary cysts. (orig.) [de

  16. [Mesenchymal gastric tumor--not always GIST].

    Science.gov (United States)

    Grosse-Holz, M; Sackmann, M; Seitz, G

    2015-02-01

    The correct histopathological classification of a gastric mesenchymal tumor as a schwannoma is essential because in contrast to gastrointestinal stromal tumors (GIST) it is a definitive benign neoplasm which can be sufficiently treated by in sano (R0) resection. A (partial) gastrectomy is unnecessary. A clear radiological or sonographical differentiation between a schwannoma and GIST is not possible. The histomorphological and immunohistochemical features of this tumor entity are described.

  17. Epithelial–Mesenchymal Transition in Ovarian Carcinoma

    Science.gov (United States)

    Davidson, Ben; Tropé, Claes G.; Reich, Reuven

    2012-01-01

    Ovarian cancer is the most lethal gynecologic malignancy, with the majority of patients dying within 5 years of diagnosis. This poor survival of patients diagnosed with this malignancy is attributed to diagnosis at advanced stage, when the tumor has metastasized, and to chemotherapy resistance, either primary or developing along tumor progression. However, ovarian carcinomas, constituting the vast majority of ovarian cancers, additionally have unique biology, one aspect of which is the ability to co-express epithelial and mesenchymal determinants. epithelial–mesenchymal transition (EMT), a physiological process by which mesenchymal cells are formed and migrate to target organs during embryogenesis, is involved in cancer cell invasion and metastasis. However, these changes do not fully occur in ovarian carcinoma, and are even reversed in tumor cells present in malignant peritoneal and pleural effusions. This review summarizes current knowledge in this area, including the characteristics of EMT related to adhesion, transcriptional regulation and chemoresistance, and their clinical relevance, as well as the recently observed regulation of EMT by microRNA. PMID:22655269

  18. Epithelial–Mesenchymal Transition in Ovarian Carcinoma

    International Nuclear Information System (INIS)

    Davidson, Ben; Tropé, Claes G.; Reich, Reuven

    2012-01-01

    Ovarian cancer is the most lethal gynecologic malignancy, with the majority of patients dying within 5 years of diagnosis. This poor survival of patients diagnosed with this malignancy is attributed to diagnosis at advanced stage, when the tumor has metastasized, and to chemotherapy resistance, either primary or developing along tumor progression. However, ovarian carcinomas, constituting the vast majority of ovarian cancers, additionally have unique biology, one aspect of which is the ability to co-express epithelial and mesenchymal determinants. epithelial–mesenchymal transition (EMT), a physiological process by which mesenchymal cells are formed and migrate to target organs during embryogenesis, is involved in cancer cell invasion and metastasis. However, these changes do not fully occur in ovarian carcinoma, and are even reversed in tumor cells present in malignant peritoneal and pleural effusions. This review summarizes current knowledge in this area, including the characteristics of EMT related to adhesion, transcriptional regulation and chemoresistance, and their clinical relevance, as well as the recently observed regulation of EMT by microRNA.

  19. Mesenchymal dental stem cells in regenerative dentistry.

    Science.gov (United States)

    Rodríguez-Lozano, Francisco-Javier; Insausti, Carmen-Luisa; Iniesta, Francisca; Blanquer, Miguel; Ramírez, María-del-Carmen; Meseguer, Luis; Meseguer-Henarejos, Ana-Belén; Marín, Noemí; Martínez, Salvador; Moraleda, José-María

    2012-11-01

    In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in the known of growth factors and signalling molecules implicated in tooth development and regeneration of different structures of teeth. Furthermore, these cells need a fabulous scaffold that facility their integration, differentiation, matrix synthesis and promote multiple specific interactions between cells. In this review, we give a brief description of tooth development and anatomy, definition and classification of stem cells, with special attention of mesenchymal stem cells, commonly used in the cellular therapy for their trasdifferentiation ability, non ethical problems and acceptable results in preliminary clinical trials. In terms of tissue engineering, we provide an overview of different types of mesenchymal stem cells that have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs), growth factors implicated in regeneration teeth and types of scaffolds for dental tissue regeneration.

  20. Case report

    African Journals Online (AJOL)

    abp

    2015-07-23

    Jul 23, 2015 ... Fletcher CDM, Unni K, Martens F, eds. World Health. Organization Classification of Tumour, Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002;. 213-15. Google Scholar. 10. Weiss SW, Goldblum JR. Extraskeletal myxoid chondrosarcoma. In: Weiss SW, Goldblum JR, eds.

  1. Mesenchymal hamartoma of the liver: a case report

    International Nuclear Information System (INIS)

    Alwaidh, M.H.; Woodhall, C.R.; Carty, H.T.

    1997-01-01

    A 6-month-old boy presented with a large abdominal mass that proved to be a cystic hepatic mesenchymal hamartoma occupying both hepatic lobes. During fetal life, a bulky, abnormal, cystic placenta had been present, which on histological examination was diagnosed as mesenchymal stem villous hyperplasia. This association has not previously been reported. (orig.)

  2. Possible mechanism of disintegrin/like domain in mesenchymal ...

    African Journals Online (AJOL)

    Liver disease is one of the major health problems in many countries. Mesenchymal Stem cells have opened a new approach to deal with liver fibrosis. Improvement of bone marrow derived mesenchymal stem cellshoming after systemic injection of disintegrin/like domain purified from Egyptian horned Cerastes cerastes ...

  3. Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit), and YKL-40

    DEFF Research Database (Denmark)

    Daugaard, Søren; Christensen, Lise H; Høgdall, Estrid

    2009-01-01

    (s) for the different subgroups. Archival material from three extraskeletal myxoid chondrosarcomas, five chordomas, five chondromyxoid fibromas, five chondroblastomas and 25 chondrosarcomas was stained with antibodies against osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit) and YKL......-40. All 25 chondrosarcomas showed a positive staining reaction for D2-40, none for actin and CD117, and a partial reactivity for bcl-2 (36%). Chondroblastomas (5/5) and chondromyxoid fibromas (2/5) were the only tumors with a positive reaction for actin, and all chondroblastomas (n=5...... chondrosarcomas. A convincing immunoreactivity for calponin and/or actin in chondromyxoid fibromas and chondroblastomas may also be helpful in differentiating these tumors from chondrosarcomas....

  4. 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.

  5. Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

    Science.gov (United States)

    2012-02-01

    10-1-0927 TITLE: Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation...immunosuppression. Bone Marrow Derived Mesenchymal stem cells (BM-MSCs) are pluripotent cells, capable of differentiation along multiple mesenchymal lineages into...As part of implemented transition from University of Pittsburgh to Johns Hopkins University, we optimized our mesenchymal stem cell (MSC) isolation

  6. Chondrosarcoma in Hereditary Multiple Exostosis

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... There was minimal calcification in this tissue (Fig. 2). Fig. 2. Case 2. Radiography of a section of the scapular tumour. The bony element is small and most of the lesion consists of a large cartilaginons 'cap'. Histological examination of numerous different segments failed to reveal any sign of malignancy.

  7. Viability of mesenchymal stem cells during electrospinning

    Directory of Open Access Journals (Sweden)

    G. Zanatta

    2012-02-01

    Full Text Available Tissue engineering is a technique by which a live tissue can be re-constructed and one of its main goals is to associate cells with biomaterials. Electrospinning is a technique that facilitates the production of nanofibers and is commonly used to develop fibrous scaffolds to be used in tissue engineering. In the present study, a different approach for cell incorporation into fibrous scaffolds was tested. Mesenchymal stem cells were extracted from the wall of the umbilical cord and mononuclear cells from umbilical cord blood. Cells were re-suspended in a 10% polyvinyl alcohol solution and subjected to electrospinning for 30 min under a voltage of 21 kV. Cell viability was assessed before and after the procedure by exclusion of dead cells using trypan blue staining. Fiber diameter was observed by scanning electron microscopy and the presence of cells within the scaffolds was analyzed by confocal laser scanning microscopy. After electrospinning, the viability of mesenchymal stem cells was reduced from 88 to 19.6% and the viability of mononuclear cells from 99 to 8.38%. The loss of viability was possibly due to the high viscosity of the polymer solution, which reduced the access to nutrients associated with electric and mechanical stress during electrospinning. These results suggest that the incorporation of cells during fiber formation by electrospinning is a viable process that needs more investigation in order to find ways to protect cells from damage.

  8. Placental Mesenchymal Dysplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachna Agarwal

    2012-01-01

    Full Text Available Introduction. A rare case of histologically proven placental mesenchymal dysplasia (PMD with fetal omphalocele in a 22-year-old patient is reported. Material and Methods. Antenatal ultrasound of this patient showed hydropic placenta with a live fetus of 17 weeks period of gestation associated with omphalocele. Cordocentesis detected the diploid karyotype of the fetus. Patient, when prognosticated, choose to terminate the pregnancy in view of high incidence of fetal and placental anomalies. Subsequent histopathological examination of placenta established the diagnosis to be placental mesenchymal dysplasia. Conclusion. On clinical and ultrasonic grounds, suspicion of P.M.D. arises when hydropic placenta with a live fetus presents in second trimester of pregnancy. Cordocentesis can detect the diploid karyotype of the fetus in such cases. As this condition is prognostically better than triploid partial mole, continuation of pregnancy can sometimes be considered after through antenatal screening and patient counseling. However, a definite diagnosis of P.M.D. is made only on placental histology by absence of trophoblast hyperplasia and trophoblastic inclusions.

  9. Mesenchymal stem cells in multiple sclerosis - translation to clinical trials.

    Science.gov (United States)

    Dulamea, A

    2015-01-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by an aberrant activation of the immune system and combining demyelination with neurodegeneration. Studies on experimental models of multiple sclerosis revealed immunomodulatory and immunosuppressive properties of mesenchymal stem cells. Clinical trials using mesenchymal stem cells therapy in multiple sclerosis patients showed tolerability, safety on short term, some immunomodulatory properties reducing the Th1 proinflammatory response and the inflammatory MRI parameters. The author reviews the data about experimental studies and clinical trials using mesenchymal stem cells for the treatment of multiple sclerosis.

  10. Histone signature of metanephric mesenchyme cell lines.

    Science.gov (United States)

    McLaughlin, Nathan; Yao, Xiao; Li, Yuwen; Saifudeen, Zubaida; El-Dahr, Samir S

    2013-09-01

    The metanephric mesenchyme (MM) gives rise to nephrons, the filtering units of the mature kidney. The MM is composed of uninduced (Six2(high)/Lhx1(low)) and induced (Wnt-stimulated, Six2(low)/Lhx1(high)) cells. The global epigenetic state of MM cells is unknown, partly due to technical difficulty in isolating sufficient numbers of homogenous cell populations. We therefore took advantage of two mouse clonal cell lines representing the uninduced (mK3) and induced (mK4) metanephric mesenchyme (based on gene expression profiles and ability to induce branching of ureteric bud). ChIP-Seq revealed that whereas H3K4me3 active region "peaks" are enriched in metabolic genes, H3K27me3 peaks decorate mesenchyme and epithelial cell fate commitment genes. In uninduced mK3 cells, promoters of "stemness" genes (e.g., Six2, Osr1) are enriched with H3K4me3 peaks; these are lost in induced mK4 cells. ChIP-qPCR confirmed this finding and further demonstrated that G9a/H3K9me2 occupy the promoter region of Six2 in induced cells, consistent with the inactive state of transcription. Conversely, genes that mark the induced epithelialized state (e.g., Lhx1, Pax8), transition from a non-permissive to an active chromatin signature in mK3 vs. mK4 cells, respectively. Importantly, stimulation of Wnt signaling in uninduced mK3 cells provokes an active chromatin state (high H3K4me3, low H3K27me3), recruitment of β-catenin, and loss of pre-bound histone methyltransferase Ezh2 in silent induced genes followed by activation of transcription. We conclude that the chromatin signature of uninduced and induced cells correlates strongly with their gene expression states, suggesting a role of chromatin-based mechanisms in MM cell fate.

  11. SIGNALING PATHWAYS ASSOCIATED WITH VX EXPOSURE IN MESENCHYMAL STEM CELLS

    Science.gov (United States)

    2017-09-01

    administrative support. iv  Blank v  CONTENTS 1. INTRODUCTION...M.J.; Cheng, A.; Genever, P.G. Functional Nicotinic and Muscarinic Receptors on Mesenchymal Stem Cells. Stem Cells Dev. 2009, 18, 103–112. 12

  12. Cryopreservation and revival of human mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Haack-Sørensen, Mandana; Ekblond, Annette; Kastrup, Jens

    2016-01-01

    Cell-based therapy is a promising and innovative new treatment for different degenerative and autoimmune diseases, and mesenchymal stromal cells (MSCs) from the bone marrow have demonstrated great therapeutic potential due to their immunosuppressive and regenerative capacities. The establishment...

  13. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.

    2015-01-01

    and their responses to diverse stimuli, however, the role of autophagy in glucocorticoidinduced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy...

  14. The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma

    NARCIS (Netherlands)

    Bhat, Krishna P. L.; Salazar, Katrina L.; Balasubramaniyan, Veerakumar; Wani, Khalida; Heathcock, Lindsey; Hollingsworth, Faith; James, Johanna D.; Gumin, Joy; Diefes, Kristin L.; Kim, Se Hoon; Turski, Alice; Azodi, Yasaman; Yang, Yuhui; Doucette, Tiffany; Colman, Howard; Sulman, Erik P.; Lang, Frederick F.; Rao, Ganesh; Copray, Sjef; Vaillant, Brian D.; Aldape, Kenneth D.

    2011-01-01

    Recent molecular classification of glioblastoma (GBM) has shown that patients with a mesenchymal (MES) gene expression signature exhibit poor overall survival and treatment resistance. Using regulatory network analysis of available expression microarray data sets of GBM, including The Cancer Genome

  15. Labeling and Imaging Mesenchymal Stem Cells with Quantum Dots

    Science.gov (United States)

    Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into bone, cartilage, adipose and muscle cells. Adult derived MSCs are being actively investigated because of their potential to be utilized for therapeutic cell-based transplantation. Methods...

  16. Mesenchymal stem cell therapy for nonmusculoskeletal diseases: emerging applications.

    Science.gov (United States)

    Kuo, Tom K; Ho, Jennifer H; Lee, Oscar K

    2009-01-01

    Mesenchymal stem cells are stem/progenitor cells originated from the mesoderm and can different into multiple cell types of the musculoskeletal system. The vast differentiation potential and the relative ease for culture expansion have established mesenchymal stem cells as the building blocks in cell therapy and tissue engineering applications for a variety of musculoskeletal diseases, including repair of fractures and bone defects, cartilage regeneration, treatment of osteonecrosis of the femoral head, and correction of genetic diseases such as osteogenesis imperfect. However, research in the past decade has revealed differentiation potentials of mesenchymal stem cells beyond lineages of the mesoderm, suggesting broader applications than originally perceived. In this article, we review the recent developments in mesenchymal stem cell research with respect to their emerging properties and applications in nonmusculoskeletal diseases.

  17. Mesenchymal Stem Cells: Angels or Demons?

    Directory of Open Access Journals (Sweden)

    Rebecca S. Y. Wong

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment.

  18. Treatment of osteoarthritis with mesenchymal stem cells.

    Science.gov (United States)

    Wang, Wen; Cao, Wei

    2014-06-01

    Osteoarthritis (OA) is one of the most prevalent joint diseases with prominent symptoms affecting the daily life of millions of middle aged and elderly people. Despite this, there are no successful medical interventions that can prevent the progressive destruction of OA joints. The onset of pathological changes in OA is associated with deviant activity of mesenchymal stem cells (MSCs), the multipotent precursors of connective tissue cells that reside in joints. Current therapies for OA have resulted in poor clinical outcomes without repairing the damaged cartilage. Intra-articular delivery of culture-expanded MSCs has opened new avenues of OA treatment. Pre-clinical and clinical trials demonstrated the feasibility, safety, and efficacy of MSC therapy. The Wnt/β-catenin, bone morphogenetic protein 2, Indian hedgehog, and Mitogen-activated protein kinase signaling pathways have been demonstrated to be involved in OA and the mechanism of action of MSC therapies.

  19. Endothelial-Mesenchymal Transition in Regenerative Medicine.

    Science.gov (United States)

    Medici, Damian

    2016-01-01

    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.

  20. Activation and Differentiation of Mesenchymal Stem Cells.

    Science.gov (United States)

    Mishra, Pravin J; Banerjee, Debabrata

    2017-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells and exhibit two main characteristics that define stem cells: self-renewal and differentiation. MSCs can migrate to sites of injury, inflammation, and tumor. Moreover, MSCs undergo myofibroblast like differentiation, including increased production of α-SMA in response to transforming growth factor-β (TGF-β), a growth factor commonly secreted by tumor cells to evade immune surveillance. Based on our previous finding hMSCs become activated and resemble carcinoma-associated myofibroblasts upon prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells. Here, we show that keratinocyte conditioned medium (KCM) induces differentiation of MSCs to resemble dermal myofibroblast like cells using immunofluorescence techniques demonstrating punctate vinculin staining, and F-actin filaments.

  1. Mesenchymal stem cell therapy for laryngotracheal stenosis

    DEFF Research Database (Denmark)

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

    2017-01-01

    studies addressing the effect of MSC therapy on the airway. We assessed effect on inflammation, fibrosis, and MSC as a component in tissue engineering for treating defects in the airway. RESULTS: We identified eleven studies (n = 256 animals) from eight countries evaluating the effect of MSCs......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...... promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways. METHODS: PubMed, EMBASE, Google Scholar and the Cochrane Library were systematically searched from January 1980-January 2017 with the purpose of identifying all...

  2. Cryopreservation and revival of mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Haack-Sørensen, Mandana; Kastrup, Jens

    2011-01-01

    Over the past few years, the pace of preclinical stem cell research is astonishing and adult stem cells have become the subject of intense research. Due to the presence of promising supporting preclinical data, human clinical trials for stem cell regenerative treatment of various diseases have been...... initiated. As there has been a precedent for the use of bone marrow stem cells in the treatment of hematological malignancies and ischemic heart diseases through randomized clinical safety and efficacy trials, the development of new therapies based on culture-expanded human mesenchymal stromal cells (MSCs......) opens up new possibilities for cell therapy. To facilitate these applications, cryopreservation and long-term storage of MSCs becomes an absolute necessity. As a result, optimization of this cryopreservation protocol is absolutely critical. The major challenge during cellular cryopreservation...

  3. Receptor control in mesenchymal stem cell engineering

    Science.gov (United States)

    Dalby, Matthew J.; García, Andrés J.; Salmeron-Sanchez, Manuel

    2018-03-01

    Materials science offers a powerful tool to control mesenchymal stem cell (MSC) growth and differentiation into functional phenotypes. A complex interplay between the extracellular matrix and growth factors guides MSC phenotypes in vivo. In this Review, we discuss materials-based bioengineering approaches to direct MSC fate in vitro and in vivo, mimicking cell-matrix-growth factor crosstalk. We first scrutinize MSC-matrix interactions and how the properties of a material can be tailored to support MSC growth and differentiation in vitro, with an emphasis on MSC self-renewal mechanisms. We then highlight important growth factor signalling pathways and investigate various materials-based strategies for growth factor presentation and delivery. Integrin-growth factor crosstalk in the context of MSC engineering is introduced, and bioinspired material designs with the potential to control the MSC niche phenotype are considered. Finally, we summarize important milestones on the road to MSC engineering for regenerative medicine.

  4. Protons Sensitize Epithelial Cells to Mesenchymal Transition

    Science.gov (United States)

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M.; Pluth, Janice M.; Cucinotta, Francis A.

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1. PMID:22844446

  5. Epigenetic regulation of osteogenesis: human embryonic palatal mesenchymal cells

    OpenAIRE

    Barkhordarian, Andre; Sison, Jay; Cayabyab, Riana; Mahanian, Nicole; Chiappelli, Francesco

    2011-01-01

    Mesenchymal stem cells (MSCs) provide an appropriate model to study epigenetic changes during osteogenesis and bone regeneration due to their differentiation potential. Since there are no unique markers for MSCs, methods of identification are limited. The complex morphology of human embryonic palatal mesenchyme stem cell (HEPM) requires analysis of fractal dimensions to provide an objective quantification of self-similarity, a statistical transformation of cellular shape and border complexity...

  6. Mesenchymal stem cells in synovial fluid increase after meniscus injury.

    Science.gov (United States)

    Matsukura, Yu; Muneta, Takeshi; Tsuji, Kunikazu; Koga, Hideyuki; Sekiya, Ichiro

    2014-05-01

    Although relatively uncommon, spontaneous healing from a meniscus injury has been observed even within the avascular area. This may be the result of the existence of mesenchymal stem cells in synovial fluid. The purpose of this study was to investigate whether mesenchymal stem cells existed in the synovial fluid of the knee after meniscus injury. Synovial fluid was obtained from the knees of 22 patients with meniscus injury just before meniscus surgery and from 8 volunteers who had no history of knee injury. The cellular fraction of the synovial fluid was cultured for 14 days followed by analysis for multilineage potential and presentation of surface antigens characteristic of mesenchymal stem cells. Colony-forming efficiency and proliferation potential were also compared between the two groups. Cells with characteristics of mesenchymal stem cells were observed in the synovial fluid of injured knees to a much greater degree than in uninjured knees. The colony-forming cells derived from the synovial fluid of the knee with meniscus injury had multipotentiality and surface epitopes identical to mesenchymal stem cells. The average number of colony formation, obtained from 1 mL of synovial fluid, in meniscus-injured knees was 250, higher than that from healthy volunteers, which was 0.5 (p < 0.001). Total colony number per synovial fluid volume was positively correlated with the postinjury period (r = 0.77, p < 0.001). Mesenchymal stem cells were found to exist in synovial fluid from knees after meniscus injury. Mesenchymal stem cells were present in higher numbers in synovial fluid with meniscus injury than in normal knees. Total colony number per synovial fluid volume was positively correlated with the postinjury period. Our current human study and previous animal studies suggest the possibility that mesenchymal stem cells in synovial fluid increase after meniscus injury contributing to spontaneous meniscus healing.

  7. Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs

    DEFF Research Database (Denmark)

    Rowe, R.G.; Li, X.Y.; Hu, Y.

    2009-01-01

    Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. Whet...

  8. Comparison of Alternative Mesenchymal Stem Cell Sources for Cell Banking and Musculoskeletal Advanced Therapies

    NARCIS (Netherlands)

    Cavallo, Carola; Cuomo, Carmela; Fantini, Sara; Ricci, Francesca; Tazzari, Pier Luigi; Lucarelli, Enrico; Donati, Davide; Facchini, Andrea; Lisignoli, Gina; Fornasari, Pier Maria; Grigolo, Brunella; Moroni, Lorenzo

    2011-01-01

    With the continuous discovery of new alternative sources containing mesenchymal stem cells (MSCs), regenerative medicine therapies may find tailored applications in the clinics. Although these cells have been demonstrated to express specific mesenchymal markers and are able to differentiate into

  9. Monoclonal Antibodies against Differentiating Mesenchyme Cells in Larvae of the Ascidian Halocynthia roretzi

    OpenAIRE

    Gil Jung, Kim; Hiroki, Nishida; Department of Life Science, Tokyo Institute of Technology, Nagatsuta; Department of Life Science, Tokyo Institute of Technology, Nagatsuta

    1998-01-01

    Mechanisms of cell specification of mesenchyme during ascidian embryogenesis are poorly understood. This is because no good molecular markers have been available to evaluate differentiation of the mesenchyme cells. To obtain molecular markers of mesenchyme differentiation, we established monoclonal antibodies, Mch-1 and Mch-3, that recognize antigens present in the mesenchyme cells of the larva of Halocynthia roretzi. The antigens recognized by both antibodies start to be detectable in the me...

  10. Collagen cross-linking by adipose-derived mesenchymal stromal cells and scar-derived mesenchymal cells: Are mesenchymal stromal cells involved in scar formation?

    NARCIS (Netherlands)

    Bogaerdt, van den A.J.; Veen, van der A.G.; Zuijlen, van P.P.; Reijnen, L.; Verkerk, M.; Bank, R.A.; Middelkoop, E.; Ulrich, M.

    2009-01-01

    In this work, different fibroblast-like (mesenchymal) cell populations that might be involved in wound healing were characterized and their involvement in scar formation was studied by determining collagen synthesis and processing. Depending on the physical and mechanical properties of the tissues,

  11. Collagen cross-linking by adipose-derived mesenchymal stromal cells and scar-derived mesenchymal cells : Are mesenchymal stromal cells involved in scar formation?

    NARCIS (Netherlands)

    van den Bogaerdt, Antoon J.; van der Veen, Vincent C.; van Zuijlen, Paul P. M.; Reijnen, Linda; Verkerk, Michelle; Bank, Ruud A.; Middelkoop, Esther; Ulrich, Magda M. W.

    2009-01-01

    In this work, different fibroblast-like (mesenchymal) cell populations that might be involved in wound healing were characterized and their involvement in scar formation was studied by determining collagen synthesis and processing. Depending on the physical and mechanical properties of the tissues,

  12. Mesenchymal cells for skeletal tissue engineering.

    Science.gov (United States)

    Panetta, N J; Gupta, D M; Quarto, N; Longaker, M T

    2009-03-01

    Today, surgical intervention remains the mainstay of treatment to intervene upon a multitude of skeletal deficits and defects attributable to congenital malformations, oncologic resection, pathologic degenerative bone destruction, and post-traumatic loss. Despite this significant demand, the tools with which surgeons remain equipped are plagued with a surfeit of inadequacies, often resulting in less than ideal patient outcomes. The failings of current techniques largely arise secondary to their inability to produce a regenerate which closely resembles lost tissue. As such, focus has shifted to the potential of mesenchymal stem cell (MSC)-based skeletal tissue engineering. The successful development of such techniques would represent a paradigm shift from current approaches, carrying with it the potential to regenerate tissues which mimic the form and function of endogenous bone. Lessons learned from investigations probing the endogenous regenerative capacity of skeletal tissues have provided direction to early studies investigating the osteogenic potential of MSC. Additionally, increasing attention is being turned to the role of targeted molecular manipulations in augmenting MSC osteogenesis, as well as the development of an ideal scaffold ''vehicle'' with which to deliver progenitor cells. The following discussion presents the authors' current working knowledge regarding these critical aspects of MSC application in cell-based skeletal tissue engineering strategies, as well as provides insight towards what future steps must be taken to make their clinical translation a reality.

  13. Gut Mesenchymal Stromal Cells in Immunity

    Directory of Open Access Journals (Sweden)

    Valeria Messina

    2017-01-01

    Full Text Available Mesenchymal stromal cells (MSCs, first found in bone marrow (BM, are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal or interspersed within intestinal submucosa (intercryptal. In Crohn’s disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC. The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFNγ is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn’s disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer.

  14. Mesenchymal Stem Cells in Tissue Repair

    Directory of Open Access Journals (Sweden)

    Amy M DiMarino

    2013-09-01

    Full Text Available The advent of mesenchymal stem cell (MSC based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control (QC and quality assurance (QA are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC’s participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency Are important new topics. In this regard,,, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.

  15. Transcriptional networks in epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Christo Venkov

    Full Text Available Epithelial-mesenchymal transition (EMT changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis.Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding these CREs, establish their importance in the initiation and propagation of EMT. Oligonucleotides that block the most frequent CREs restrain EMT at early and intermediate stages through apoptosis of the cells.Our results identify new transcriptional interactions with high frequency CREs that modulate the stability of cellular plasticity, and may serve as targets for modulating these transitional states in fibroblasts.

  16. Application of mesenchymal stem cells in paediatrics

    Directory of Open Access Journals (Sweden)

    Wawryk-Gawda Ewelina

    2017-09-01

    Full Text Available Mesenchymal stem cells (MSC were described by Friedenstein in the 1970s as being a group of bone marrow non-hematopoietic cells that are the source of fibroblasts. Since then, knowledge about the therapeutic potential of MSCs has significantly increased. MSCs are currently used for the treatment of many diseases, both in adults and children. MSCs are used successfully in the case of autoimmune diseases, including rheumatic diseases, diabetes mellitus type 1, gastroenterological and neurological diseases. Moreover, treatment of such organ disorders as damage or hypoxia through application of MSC therapy has shown to be satisfactory. In addition, there are some types of congenital disorders, including osteogenesis imperfecta and Spinal Muscular Atrophy, that may be treated with cellular therapy. Most studies showed no other adverse effects than fever. Our study is an analysis that particularly focuses on the registered trials and results of MSCs application to under 18 patients with acute, chronic, recurrent, resistance and corticosteroids types of Graft-versus-Host Disease (GvHD. Stem cells currently play an important role in the treatment of many diseases. Long-term studies conducted on animals have shown that cell therapy is both effective and safe. The number of indications for use of these cells in the course of treatment of people is constantly increasing. The results of subsequent studies provide important data justifying the application of MSCs in the course of treatment of many diseases whose treatment is ineffective when utilizing other approaches.

  17. Mesenchymal Wnt/β-catenin signaling limits tooth number.

    Science.gov (United States)

    Järvinen, Elina; Shimomura-Kuroki, Junko; Balic, Anamaria; Jussila, Maria; Thesleff, Irma

    2018-02-21

    Tooth agenesis is one of the predominant developmental anomalies in humans, usually affecting the permanent dentition generated by sequential tooth formation and, in most cases, caused by mutations perturbing epithelial Wnt/β-catenin signaling. In addition, loss-of-function mutations in the Wnt feedback inhibitor AXIN2 lead to human tooth agenesis. We have investigated the functions of Wnt/β-catenin signaling during sequential formation of molar teeth using mouse models. Continuous initiation of new teeth, which is observed after genetic activation of Wnt/β-catenin signaling in the oral epithelium, was accompanied by enhanced expression of Wnt antagonists and a downregulation of Wnt/β-catenin signaling in the dental mesenchyme. Genetic and pharmacological activation of mesenchymal Wnt/β-catenin signaling negatively regulated sequential tooth formation, an effect partly mediated by Bmp4. Runx2 , a gene whose loss-of-function mutations result in sequential formation of supernumerary teeth in the human cleidocranial dysplasia syndrome, suppressed the expression of Wnt inhibitors Axin2 and Drapc1 in dental mesenchyme. Our data indicate that increased mesenchymal Wnt signaling inhibits the sequential formation of teeth, and suggest that Axin2 / Runx2 antagonistic interactions modulate the level of mesenchymal Wnt/β-catenin signaling, underlying the contrasting dental phenotypes caused by human AXIN2 and RUNX2 mutations. © 2018. Published by The Company of Biologists Ltd.

  18. Radiological Spectrum of Hepatic Mesenchymal Hamartoma in Children

    International Nuclear Information System (INIS)

    Kim, Soung Hee; Kim, Woo Sun; Cheon, Jung Eun; Kang, Gyeong Hoon; Kim, In One; Yeon, Kyung Mo; Yoon, Hye Kyung

    2007-01-01

    A hepatic mesenchymal hamartoma is an uncommon benign tumor in children and little is known about the spectrum of its radiological features. The purpose of this study is to describe the spectrum of radiological features of a hepatic mesenchymal hamartoma in children. Thirteen children with a pathologically confirmed hepatic mesenchymal hamartoma (M:F = 7:6; mean age, 3 years 2 months) were included in our study. Ultrasonography (US) was performed in nine patients including color and power Doppler US (n = 7). CT scans were performed in all patients. We evaluated the imaging findings of the hepatic mesenchymal hamartomas and the corresponding pathological features. Each patient had a single tumor (mean diameter: 13 cm [1.8-20 cm]). On CT and/or US, four patients (31%) had a 'multiseptated cystic tumor', five patients (38%) had a 'mixed solid and cystic tumor', and four patients (31%) had a 'solid tumor.' The septa of the cystic portion were thin in the multiseptated cystic tumors and irregularly thick in the mixed solid and cystic tumors as seen on US. On a post-contrast CT scan, solid portions or thick septa of the tumors showed heterogeneous enhancement. The amount of hepatocytes was significantly different among the three tumor groups according to the imaging spectrum (p = 0.042). A hepatic mesenchymal hamartoma in children can show a wide spectrum of radiological features, from a multiseptated cystic tumor to a mixed solid and cystic tumor, and even a solid tumor

  19. Glial origin of mesenchymal stem cells in a tooth model system

    NARCIS (Netherlands)

    Kaukua, Nina; Shahidi, Maryam Khatibi; Konstantinidou, Chrysoula; Dyachuk, Vyacheslav; Kaucka, Marketa; Furlan, Alessandro; An, Zhengwen; Wang, Longlong; Hultman, Isabell; Ahrlund-Richter, Lars; Blom, Hans; Brismar, Hjalmar; Lopes, Natalia Assaife; Pachnis, Vassilis; Suter, Ueli; Clevers, Hans; Thesleff, Irma; Sharpe, Paul; Ernfors, Patrik; Fried, Kaj; Adameyko, Igor

    2014-01-01

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells

  20. Comparative studies on the skeletogenic mesenchyme of echinoids.

    Science.gov (United States)

    Minokawa, Takuya

    2017-07-15

    Skeletogenic mesenchyme cells in echinoids are suitable for studying developmental mechanisms, and have been used extensively. Most of these studies have been performed on species in the order Camarodonta, which are modern echinoids (subclass Euechinoidea) and are considered "model" echinoid species. In contrast, species belonging to other orders are studied less frequently, especially investigations of their molecular developmental biology such as gene regulatory networks. Recent studies on mesenchyme development in non-camarodont species suggest that these species are potential sources of comparative information to elucidate the mechanisms underlying skeletogenic mesenchyme development. In this review, the importance of using comparative data to understand development and evolution is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The role of endothelial-mesenchymal transition in heterotopic ossification

    Science.gov (United States)

    Medici, Damian; Olsen, Bjorn R.

    2012-01-01

    Heterotopic ossification (HO) is a process by which bone forms in soft tissues, in response to injury, inflammation or genetic disease. This usually occurs by initial cartilage formation, followed by endochondral ossification. A rare disease called Fibrodysplasia Ossificans Progressiva (FOP) allows this mechanism to be induced by a combination of genetic mutation and acute inflammatory responses. FOP patients experience progressive HO throughout their lifetime and form an ectopic skeleton. Recent studies on FOP have suggested that heterotopic cartilage and bone is of endothelial origin. Vascular endothelial cells differentiate into skeletal cells through a mesenchymal stem cell intermediate that is generated by endothelial-mesenchymal transition (EndMT). Local inflammatory signals and/or other changes in the tissue microenvironment mediate the differentiation of endothelial-derived mesenchymal stem cells into chondrocytes and osteoblasts to induce HO. Here we discuss the current evidence for the endothelial contribution to heterotopic bone formation. PMID:22806925

  2. A role for mesenchyme dynamics in mouse lung branching morphogenesis.

    Directory of Open Access Journals (Sweden)

    Pierre Blanc

    Full Text Available Mammalian airways are highly ramified tree-like structures that develop by the repetitive branching of the lung epithelium into the surrounding mesenchyme through reciprocal interactions. Based on a morphometric analysis of the epithelial tree, it has been recently proposed that the complete branching scheme is specified early in each lineage by a programme using elementary patterning routines at specific sites and times in the developing lung. However, the coupled dynamics of both the epithelium and mesenchyme have been overlooked in this process. Using a qualitative and quantitative in vivo morphometric analysis of the E11.25 to E13.5 mouse whole right cranial lobe structure, we show that beyond the first generations, the branching stereotypy relaxes and both spatial and temporal variations are common. The branching pattern and branching rate are sensitive to the dynamic changes of the mesoderm shape that is in turn mainly dependent upon the volume and shape of the surrounding intrathoracic organs. Spatial and temporal variations of the tree architecture are related to local and subtle modifications of the mesoderm growth. Remarkably, buds never meet after suffering branching variations and continue to homogenously fill the opening spaces in the mesenchyme. Moreover despite inter-specimen variations, the growth of the epithelial tree and the mesenchyme remains highly correlated over time at the whole lobe level, implying a long-range regulation of the lung lobe morphogenesis. Together, these findings indicate that the lung epithelial tree is likely to adapt in real time to fill the available space in the mesenchyme, rather than being rigidly specified and predefined by a global programme. Our results strongly support the idea that a comprehensive understanding of lung branching mechanisms cannot be inferred from the branching pattern or behavior alone. Rather it needs to be elaborated upon with the reconsideration of mesenchyme

  3. Fgfr2 is integral for bladder mesenchyme patterning and function.

    Science.gov (United States)

    Ikeda, Y; Zabbarova, I; Schaefer, C M; Bushnell, D; De Groat, W C; Kanai, A; Bates, C M

    2017-04-01

    While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor 2 (Fgfr2) is necessary for kidney and ureter mesenchymal development. Our objective was to determine the role of Fgfr2 in bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in bladder mesenchyme ( Fgfr2 BM -/- ). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblotting, void stain on paper, ex vivo bladder sheet assays, and in vivo decerebrated cystometry. Compared with controls, embryonic ( E ) day 16.5 ( E16.5 ) Fgfr2 BM -/- bladders have thin muscle layers with reduced α-smooth muscle actin levels and thickened lamina propria with increased collagen expression that intrudes into muscle. From postnatal ( P ) day 1 ( P1 ) to P30 , Fgfr2 BM -/- bladders demonstrate progressive muscle loss and increased collagen expression. Postnatal Fgfr2 BM -/- bladder sheets exhibit decreased contractility and increased passive stretch tension compared with controls. In vivo cystometry revealed high baseline and threshold pressures and shortened intercontractile intervals in Fgfr2 BM -/- bladders compared with controls. Mechanistically, while Shh expression appears normal, mRNA and protein readouts of hedgehog activity are increased in E16.5 Fgfr2 BM -/- bladders compared with controls. Moreover, E16.5 Fgfr2 BM -/- bladders exhibit higher levels of Cdo and Boc , hedgehog coreceptors that enhance sensitivity to Shh, than controls. Fgfr2 is critical for bladder mesenchyme patterning by virtue of its role in modulation of hedgehog signaling. Copyright © 2017 the American Physiological Society.

  4. Inductive ability of human developing and differentiated dental mesenchyme.

    Science.gov (United States)

    Zheng, Liwei; Warotayanont, Rungnapa; Stahl, Jonathan; Kunimatsu, Ryo; Klein, Ophir; DenBesten, Pamela K; Zhang, Yan

    2013-01-01

    The development of cell-based therapeutic strategies to bioengineer tooth tissue is a promising approach for the treatment of lost or damaged tooth tissue. The lack of a readily available cell source for human dental epithelial cells (ECs) severely constrains the progress of tooth bioengineering. Previous studies in model organisms have demonstrated that developing dental mesenchyme can instruct nondental epithelium to differentiate into enamel-forming epithelium. In this study, we characterized the ability of fetal and adult human dental mesenchyme to promote differentiation of human embryonic stem cell (hESC)-derived ECs (ES-ECs) into ameloblast-lineage cells. ES-ECs were co-cultured either with human fetal dental mesenchymal cells (FDMCs) or with adult dental mesenchymal cells (ADMCs) in either a three-dimensional culture system, or in the renal capsules of SCID mice. When co-cultured with FDMCs in vitro, ES-ECs polarized and expressed amelogenin. Tooth organ-like structures assembled with epithelium and encased mesenchyme and developing enamel-like structures could be detected in the complexes resulting from in vitro and ex vivo co-culture of ES-ECs and FDMCs. In contrast, co-cultured ES-ECs and ADMCs formed amorphous spherical structures and occasionally formed hair. Transcription factors were significantly upregulated in FDMCs compared to ADMCs including MSX1, GLI1, LHX6, LHX8,LEF1 and TBX1. In summary, FDMCs but not ADMCs had the capacity to induce differentiation of ES-ECs into ameloblast lineage cells. Further characterization of the functional differences between these two types of dental mesenchyme could enable reprogramming of ADMCs to enhance their odontogenic inductive competence. © 2013 S. Karger AG, Basel

  5. A role for mesenchyme dynamics in mouse lung branching morphogenesis.

    Science.gov (United States)

    Blanc, Pierre; Coste, Karen; Pouchin, Pierre; Azaïs, Jean-Marc; Blanchon, Loïc; Gallot, Denis; Sapin, Vincent

    2012-01-01

    Mammalian airways are highly ramified tree-like structures that develop by the repetitive branching of the lung epithelium into the surrounding mesenchyme through reciprocal interactions. Based on a morphometric analysis of the epithelial tree, it has been recently proposed that the complete branching scheme is specified early in each lineage by a programme using elementary patterning routines at specific sites and times in the developing lung. However, the coupled dynamics of both the epithelium and mesenchyme have been overlooked in this process. Using a qualitative and quantitative in vivo morphometric analysis of the E11.25 to E13.5 mouse whole right cranial lobe structure, we show that beyond the first generations, the branching stereotypy relaxes and both spatial and temporal variations are common. The branching pattern and branching rate are sensitive to the dynamic changes of the mesoderm shape that is in turn mainly dependent upon the volume and shape of the surrounding intrathoracic organs. Spatial and temporal variations of the tree architecture are related to local and subtle modifications of the mesoderm growth. Remarkably, buds never meet after suffering branching variations and continue to homogenously fill the opening spaces in the mesenchyme. Moreover despite inter-specimen variations, the growth of the epithelial tree and the mesenchyme remains highly correlated over time at the whole lobe level, implying a long-range regulation of the lung lobe morphogenesis. Together, these findings indicate that the lung epithelial tree is likely to adapt in real time to fill the available space in the mesenchyme, rather than being rigidly specified and predefined by a global programme. Our results strongly support the idea that a comprehensive understanding of lung branching mechanisms cannot be inferred from the branching pattern or behavior alone. Rather it needs to be elaborated upon with the reconsideration of mesenchyme-epithelium coupled growth and lung

  6. Effects of dexamethasone on palate mesenchymal cell phospholipase activity

    International Nuclear Information System (INIS)

    Bulleit, R.F.; Zimmerman, E.F.

    1984-01-01

    Corticosteroids will induce cleft palate in mice. One suggested mechanism for this effect is through inhibition of phospholipase activity. This hypothesis was tested by measuring the effects of dexamethasone, a synthetic corticosteroid, on phospholipase activity in cultures of palate mesenchymal cells. Palate mesenchymal cells were prelabeled with [3H]arachidonic acid. The cells were subsequently treated with various concentrations of dexamethasone. Concurrently, cultures of M-MSV-transformed 3T3 cells were prepared identically. After treatment, phospholipase activity was stimulated by the addition of serum or epidermal growth factor (EGF), and radioactivity released into the medium was taken as a measure of phospholipase activity. Dexamethasone (1 X 10(-5) or 1 X 10(-4) M) could inhibit serum-stimulated phospholipase activity in transformed 3T3 cells after 1 to 24 hr of treatment. However, no inhibition of activity was measured in palate mesenchymal cells following this period of treatment. Not until 120 hr of treatment with dexamethasone (1 X 10(-4) M) was any significant inhibition of serum-stimulated phospholipase activity observed in palate mesenchymal cells. When EGF was used to stimulate phospholipase activity, dexamethasone (1 X 10(-5) M) caused an increase in phospholipase activity in palate mesenchymal cells. These observations suggested that phospholipase in transformed 3T3 cells was sensitive to inhibition by dexamethasone. However, palate mesenchymal cell phospholipase is only minimally sensitive to dexamethasone, and in certain instances can be enhanced. These results cannot support the hypothesis that corticosteroids mediate their teratogenic effect via inhibition of phospholipase activity

  7. Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

    Directory of Open Access Journals (Sweden)

    Yue Cao

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs, an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU. Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs, compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation.

  8. [Differentiation of mesenchymal stem cells of adipose tissue].

    Science.gov (United States)

    Salyutin, R V; Zapohlska, K M; Palyanytsya, S S; Sirman, V M; Sokolov, M F

    2015-03-01

    Experimental investigation were conducted with the objective to determine a stem cells, capacity to differentiate in adipogenic direction, if they were obtained from adipose tissue. The investigation results have witnessed, that the cells, obtained from adipose tissue, are capable for a tissue-speciphic differentiation in osteogenic, chondrogenic, and, principally--in adipogenic direction, what confirms a multypotent nature of mesenchymal stem cells of adipose tissue. Adipose tissue constitutes an alternative to the bone marrow, as a source of multipotent mesenchymal stem cells, which may be applied in further investigations, concerning determination of their defense possibility for the transplanted autologous adipose tissue from the tissue resorption, made in a lipophiling way.

  9. Mesenchymal Stromal Cells: Updates and Therapeutic Outlook in Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    Christian Jorgensen

    2013-10-01

    Full Text Available Multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs are adult stem cells exhibiting functional properties that have opened the way for cell-based clinical therapies. MSCs have been reported to exhibit immunosuppressive as well as healing properties, improving angiogenesis and preventing apoptosis or fibrosis through the secretion of paracrine mediators. This review summarizes recent progress on the clinical application of stem cells therapy in some inflammatory and degenerative rheumatic diseases. To date, most of the available data have been obtained in preclinical models and clinical efficacy needs to be evaluated through controlled randomized double-blind trials.

  10. Mesenchymal Stem Cells: Application for Immunomodulation and Tissue Repair

    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 diffe......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...

  11. Microencapsulation of Hepatocytes and Mesenchymal Stem Cells for Therapeutic Applications.

    Science.gov (United States)

    Meier, Raphael P H; Montanari, Elisa; Morel, Philippe; Pimenta, Joël; Schuurman, Henk-Jan; Wandrey, Christine; Gerber-Lemaire, Sandrine; Mahou, Redouan; Bühler, Leo H

    2017-01-01

    Encapsulated hepatocyte transplantation and encapsulated mesenchymal stem cell transplantation are newly developed potential treatments for acute and chronic liver diseases, respectively. Cells are microencapsulated in biocompatible semipermeable alginate-based hydrogels. Microspheres protect cells against antibodies and immune cells, while allowing nutrients, small/medium size proteins and drugs to diffuse inside and outside the polymer matrix. Microencapsulated cells are assessed in vitro and designed for experimental transplantation and for future clinical applications.Here, we describe the protocol for microencapsulation of hepatocytes and mesenchymal stem cells within hybrid poly(ethylene glycol)-alginate hydrogels.

  12. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.

    Directory of Open Access Journals (Sweden)

    Kosuke Fujita

    Full Text Available Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be

  13. Mechanics of mesenchymal contribution to clefting force in branching morphogenesis.

    Science.gov (United States)

    Wan, Xiaohai; Li, Zhilin; Lubkin, Sharon R

    2008-10-01

    Branching morphogenesis is ubiquitous and may involve several different mechanisms. Glandular morphogenesis is affected by growth, cell rearrangements, changes in the basal lamina, changes in the stromal ECM, changes in cell-cell and cell-ECM adhesions, mesenchymal contractility, and possibly other mechanisms. We have developed a 3D model of the mechanics of clefting, focusing in this paper solely on the potential role of mesenchyme-generated traction forces. The tissue mechanics are assumed to be those of fluids, and the hypothesized traction forces are modeled as advected by the deformations which they generate. We find that mesenchymal traction forces are sufficient to generate a cleft of the correct size and morphology, in the correct time frame. We find that viscosity of the tissues affects the time course of morphogenesis, and also affects the resulting form of the organ. Morphology is also strongly dependent on the initial distribution of contractility. We suggest an in vitro method of examining the role of mesenchyme in branching morphogenesis.

  14. In vitro differentiation of human umbilical cord blood mesenchymal ...

    African Journals Online (AJOL)

    May H. Hasan

    2016-08-05

    Aug 5, 2016 ... Abstract Mesenchymal stem cells (MSCs) were isolated by gradient density centrifugation from umbilical cord blood. Spindle-shaped adherent cells were permitted to grow to 70% confluence in primary culture media which was reached by day 12. Induction of differentiation started by cul- turing cells with ...

  15. In vitro differentiation of human umbilical cord blood mesenchymal ...

    African Journals Online (AJOL)

    Mesenchymal stem cells (MSCs) were isolated by gradient density centrifugation from umbilical cord blood. Spindle-shaped adherent cells were permitted to grow to 70% confluence in primary culture media which was reached by day 12. Induction of differentiation started by culturing cells with differentiation medium ...

  16. Adult Stromal (Skeletal, Mesenchymal) Stem Cells: Advances Towards Clinical Applications

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Harkness, Linda; Zaher, Walid

    2014-01-01

    Mesenchymal Stem Cells (MSC) are non-hematopoietic adult stromal cells that reside in a perivascular niche in close association with pericytes and endothelial cells and possess self-renewal and multi-lineage differentiation capacity. The origin, unique properties, and therapeutic benefits of MSC ...

  17. Hypophosphataemia-inducing mesenchymal tumour in the foot.

    Science.gov (United States)

    Bauer, Christa; Brücker, Rolf; Bützberger, Stefan; Schmid, Christoph

    2010-10-06

    Tumour-induced (or oncogenic) osteomalacia is a paraneoplastic syndrome characterised by progressive fatigue, muscle weakness, bone pain, non-healing and recurrent fractures caused by mesenchymal tumours that secrete proteins that inhibit renal phosphate transport and 1α-hydroxylation of 25-OH-vitamin D. The potentially curative treatment of choice is complete surgical excision of the tumour.

  18. Biomaterials Influence Macrophage-Mesenchymal Stem Cell Interaction In Vitro

    NARCIS (Netherlands)

    N. Grotenhuis (Nienke); S.F. De Witte (Samantha Fh); G.J.V.M. van Osch (Gerjo); Y. Bayon (Yves); J.F. Lange (Johan); Y.M. Bastiaansen-Jenniskens (Yvonne)

    2016-01-01

    textabstractBackground: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. Materials and

  19. Epithelial-mesenchymal transition is associated with increased ...

    African Journals Online (AJOL)

    Yomi

    2011-12-16

    Dec 16, 2011 ... to the changes in expressions of EMT markers. Key words: SMMC-7721, cancer stem cells, side population cells, invasion, epithelial-mesenchymal transition. INTRODUCTION. Invasion and metastasis are the most important biological characteristics of cancer and also the leading causes of death in cancer ...

  20. Mesenchymal stem cells: biological characteristics and potential clinical applications

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2004-01-01

    Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...

  1. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling.

    Directory of Open Access Journals (Sweden)

    Poulomi Ray

    Full Text Available Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF, Bone Morphogenetic Protein (BMP and Transforming Growth Factor beta (TGF-β signaling pathways. Rho Kinase (ROCK-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.

  2. Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds

    DEFF Research Database (Denmark)

    Mygind, Tina; Stiehler, Maik; Baatrup, Anette

    2007-01-01

    Culture of osteogenic cells on a porous scaffold could offer a new solution to bone grafting using autologous human mesenchymal stem cells (hMSC) from the patient. We compared coralline hydroxyapatite scaffolds with pore sizes of 200 and 500 microm for expansion and differentiation of hMSCs. We...

  3. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo P; Horsman, Michael Robert; Kassem, Moustapha

    2011-01-01

    . Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under...

  4. MRI appearance of mesenchymal tumors of the uterus

    International Nuclear Information System (INIS)

    Cornfeld, Daniel; Israel, Gary; Martel, Maritza; Weinreb, Jeffery; Schwartz, Peter; McCarthy, Shirley

    2010-01-01

    Purpose: Uterine leiomyomas are the most common uterine neoplasms. Statistically, a uterine mass with unusual imaging features is more likely to represent a leiomyoma than other uncommon uterine mesenchymal neoplasms such as leiomyosarcoma or endometrial stromal tumors. Several prior studies have attempted to identify objective imaging characteristics that differentiate these entities. The purpose of this study was to test these criteria on our patient population. Methods and materials: This retrospective study was approved by the institutional Human Investigations Committee and was performed in compliance with HIPAA regulations. Four patients with uterine leiomyosarcoma, two with stromal tumors of uncertain malignant potential (STUMP), one with endometrial stromal sarcoma, and two with mixed endometrial stromal and smooth muscle tumors were included in the study. Seventeen additional control cases of leiomyomas were selected as controls. Cases were blindly evaluated by two experienced readers. Objective criteria included T1 and T2 signal characteristics, enhancement pattern, the presence of cystic changes, and ill defined margins. Subjective criteria included individual reader gestalt. All cases had pathologic correlation. Results: None of the objective criteria were associated with the presence or absence of uterine mesenchymal neoplasm. Ill defined margins came closest to having statistical significance (p = 0.06). Reader gestalt was statistically associated with the presence of mesenchymal neoplasm for one of our readers (p = 0.02) but not for the other (p = 0.07). Conclusion: We found poor accuracy for objective imaging criteria in distinguishing leiomyomas with atypical imaging features from more clinically significant uterine mesenchymal neoplasms.

  5. Mesenchymal stem cells for the treatment of tendon disorders

    Czech Academy of Sciences Publication Activity Database

    Machová-Urdzíková, Lucia; Lesný, Petr; Syková, Eva; Jendelová, Pavla

    2013-01-01

    Roč. 6, 8A (2013), s. 14-23 ISSN 1937-6871 R&D Projects: GA ČR GAP304/10/0326 Institutional support: RVO:68378041 Keywords : Tendinophaty * Mesenchymal Stem Cells * Tendon Rupture Subject RIV: FP - Other Medical Disciplines

  6. The role of bone marrow derived mesenchymal stem cells in ...

    African Journals Online (AJOL)

    Stroke is the third most common cause of death, and a leading cause of physical disability in adults. Recovery after a major stroke is usually limited, but cell therapy, especially by application of mesenchymal stem cells (MSCs) is emerging with fixed neurologic deficits. The aim of the current study was directed to isolation ...

  7. Human bone marrow-derived mesenchymal stem cells | Nasef ...

    African Journals Online (AJOL)

    Mesenchymal stem cells (MSCs) have elicited a great clinical interest, particularly in the areas of regenerative medicine and induction of tolerance in allogeneic transplantation. Previous reports demonstrated the feasibility of transplanting MSCs, which generates new prospects in cellular therapy. Recently, injection of ...

  8. MicroRNA-197 induces epithelial-mesenchymal transition and ...

    Indian Academy of Sciences (India)

    微软用户

    Oncotarget. 6, 9160-9172. 4. Brabletz T. 2012 EMT and MET in metastasis: where are the cancer stem cells? Cancer Cell. 22, 699–701. 5. Tang J, Li Y, Wang J, Wen Z, Lai M, Zhang H. 2016 Molecular mechanisms of microRNAs in regulating epithelial-mesenchymal transitions in human cancers. Cancer Lett. 371, 301-313.

  9. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling

    Science.gov (United States)

    Ray, Poulomi; Chapman, Susan C.

    2015-01-01

    Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein (BMP) and Transforming Growth Factor beta (TGF-β) signaling pathways. Rho Kinase (ROCK)-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis. PMID:26237312

  10. white leghorn chimeras based on bone marrow mesenchymal stem

    African Journals Online (AJOL)

    white leghorn chimeras based on bone marrow mesenchymal stem cells. Xinxin Qin, Lei Rui, Wenting Zhang, Zhuyu Qiu and Zandong Li*. State Key Laboratory of Agrobiotechnology, Department of Biochemistry and Molecular Biology, College of Biological Science,. China Agricultural University, Beijing 100193, China.

  11. Proteomic techniques for characterisation of mesenchymal stem cell secretome.

    Czech Academy of Sciences Publication Activity Database

    Kupcová Skalníková, Helena

    2013-01-01

    Roč. 95, č. 12 (2013), s. 2196-2211 ISSN 0300-9084 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR TA01011466 Institutional support: RVO:67985904 Keywords : mesenchymal stem cells * secretome * exosome * conditioned medium * proteomics Subject RIV: CE - Biochemistry Impact factor: 3.123, year: 2013

  12. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...

  13. Research on human placenta-derived mesenchymal stem cells ...

    African Journals Online (AJOL)

    PCR) technology, amplified hVEGF165 gene fragments from human leukemia cells HL-60. hVEGF165 gene was reconstructed in pIRES2-EGFP and transferred into the human placenta-derived mesenchymal stem cells (HPMSCs) by ...

  14. Autologous Mesenchymal Stem Cells in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Ashu Bhasin

    2011-12-01

    Full Text Available Background: Cell transplantation is a ‘hype and hope’ in the current scenario. It is in the early stage of development with promises to restore function in chronic diseases. Mesenchymal stem cell (MSC transplantation in stroke patients has shown significant improvement by reducing clinical and functional deficits. They are feasible and multipotent and have homing characteristics. This study evaluates the safety, feasibility and efficacy of autologous MSC transplantation in patients with chronic stroke using clinical scores and functional imaging (blood oxygen level-dependent and diffusion tensor imaging techniques. Methods: Twelve chronic stroke patients were recruited; inclusion criteria were stroke lasting 3 months to 1 year, motor strength of hand muscles of at least 2, and NIHSS of 4–15, and patients had to be conscious and able to comprehend. Fugl Meyer (FM, modified Barthel index (mBI, MRC, Ashworth tone grade scale scores and functional imaging scans were assessed at baseline, and after 8 and 24 weeks. Bone marrow was aspirated under aseptic conditions and expansion of MSC took 3 weeks with animal serum-free media (Stem Pro SFM. Six patients were administered a mean of 50–60 × 106 cells i.v. followed by 8 weeks of physiotherapy. Six patients served as controls. This was a non-randomized experimental controlled trial. Results: Clinical and radiological scanning was normal for the stem cell group patients. There was no mortality or cell-related adverse reaction. The laboratory tests on days 1, 3, 5 and 7 were also normal in the MSC group till the last follow-up. The FM and mBI showed a modest increase in the stem cell group compared to controls. There was an increased number of cluster activation of Brodmann areas BA 4 and BA 6 after stem cell infusion compared to controls, indicating neural plasticity. Conclusion: MSC therapy aiming to restore function in stroke is safe and feasible. Further randomized controlled trials are needed

  15. Identification and fate mapping of the pancreatic mesenchyme.

    Science.gov (United States)

    Angelo, Jesse R; Tremblay, Kimberly D

    2018-03-01

    The murine pancreas buds from the ventral embryonic endoderm at approximately 8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc. Although it is clear that secreted signals from adjacent mesoderm-derived sources are required for both the appropriate emergence and further refinement of the pancreatic endoderm, neither the exact signals nor the requisite tissue sources have been defined in mammalian systems. Herein we use DiI fate mapping of cultured murine embryos to identify the embryonic sources of both the early inductive and later condensed pancreatic mesenchyme. Despite being capable of supporting pancreas induction from dorsal endoderm in co-culture experiments, we find that in the context of the developing embryo, the dorsal aortae as well as the paraxial, intermediate, and lateral mesoderm derivatives only transiently associate with the dorsal pancreas bud, producing descendants that are decidedly anterior to the pancreas bud. Unlike these other mesoderm derivatives, the axial (notochord) descendants maintain association with the dorsal pre-pancreatic endoderm and early pancreas bud. This fate mapping data points to the notochord as the likely inductive source in vivo while also revealing dynamic morphogenetic movements displayed by individual mesodermal subtypes. Because none of the mesoderm examined above produced the pancreatic mesenchyme that condenses around the induced bud to support exocrine and endocrine differentiation, we also sought to identify the mesodermal origins of this mesenchyme. We identify a portion of the coelomic mesoderm that contributes to the condensed pancreatic mesenchyme. In conclusion, we identify a portion of the notochord as a likely source of the signals required to induce and maintain the early dorsal pancreas bud, demonstrate that the coelomic mesothelium contributes to the dorsal and ventral pancreatic mesenchyme, and provide insight into the dynamic morphological rearrangements of mesoderm

  16. Separation of mouse embryonic facial ectoderm and mesenchyme.

    Science.gov (United States)

    Li, Hong; Williams, Trevor

    2013-04-12

    Orofacial clefts are the most frequent craniofacial defects, which affect 1.5 in 1,000 newborns worldwide. Orofacial clefting is caused by abnormal facial development. In human and mouse, initial growth and patterning of the face relies on several small buds of tissue, the facial prominences. The face is derived from six main prominences: paired frontal nasal processes (FNP), maxillary prominences (MxP) and mandibular prominences (MdP). These prominences consist of swellings of mesenchyme that are encased in an overlying epithelium. Studies in multiple species have shown that signaling crosstalk between facial ectoderm and mesenchyme is critical for shaping the face. Yet, mechanistic details concerning the genes involved in these signaling relays are lacking. One way to gain a comprehensive understanding of gene expression, transcription factor binding, and chromatin marks associated with the developing facial ectoderm and mesenchyme is to isolate and characterize the separated tissue compartments. Here we present a method for separating facial ectoderm and mesenchyme at embryonic day (E) 10.5, a critical developmental stage in mouse facial formation that precedes fusion of the prominences. Our method is adapted from the approach we have previously used for dissecting facial prominences. In this earlier study we had employed inbred C57BL/6 mice as this strain has become a standard for genetics, genomics and facial morphology. Here, though, due to the more limited quantities of tissue available, we have utilized the outbred CD-1 strain that is cheaper to purchase, more robust for husbandry, and tending to produce more embryos (12-18) per litter than any inbred mouse strain. Following embryo isolation, neutral protease Dispase II was used to treat the whole embryo. Then, the facial prominences were dissected out, and the facial ectoderm was separated from the mesenchyme. This method keeps both the facial ectoderm and mesenchyme intact. The samples obtained using this

  17. Uneven distribution pattern and increasing numbers of mesenchyme cells during development in the starfish, Asterina pectinifera.

    Science.gov (United States)

    Hamanaka, Gen; Hosaka, Eri; Kuraishi, Ritsu; Hosoya, Natsumi; Matsumoto, Midori; Kaneko, Hiroyuki

    2011-04-01

    During development, the embryos and larvae of the starfish Asterina pectinifera possess a single type of mesenchyme cell. The aim of this study was to determine the patterns of behavior of mesenchyme cells during the formation of various organs. To this end, we used a monoclonal antibody (mesenchyme cell marker) to identify the distribution patterns and numbers of mesenchyme cells. Our results revealed the following: (i) mesenchyme cell behavior differs in the formation of different organs, showing temporal variations and an uneven pattern of distribution; and (ii) mesenchyme cells continue to be generated throughout development, and their numbers are tightly regulated in proportion to total cell numbers. © 2011 The Authors. Journal compilation © 2011 Japanese Society of Developmental Biologists.

  18. Comparative Quantification of the Surfaceome of Human Multipotent Mesenchymal Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Rebecca J. Holley

    2015-03-01

    Full Text Available Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterization of their cell-surface interface limits their clinical exploitation. We have employed subcellular fractionation with quantitative discovery proteomics to define the cell-surface interface proteome of human bone marrow mesenchymal stromal/stem cells (MSCs and human umbilical cord perivascular cells (HUCPVCs. We compared cell-surface-enriched fractions from MSCs and HUCPVCs (three donors each with adult mesenchymal fibroblasts using eight-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6,000 proteins with high confidence. This approach identified 186 upregulated mesenchymal progenitor biomarkers. Validation of 10 of these markers, including ROR2, EPHA2, and PLXNA2, confirmed upregulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration, and differentiation. Our approach has delivered a cell-surface proteome repository that now enables improved selection and characterization of human mesenchymal progenitor populations.

  19. Signaling pathways regulating the expression of Prx1 and Prx2 in the Chick Mandibular Mesenchyme

    Science.gov (United States)

    Doufexi, Aikaterini-El; Mina, Mina

    2009-01-01

    Prx1 and Prx2 are members of the aristaless-related homeobox genes shown to play redundant but essential roles in morphogenesis of the mandibular processes. To gain insight into the signaling pathways that regulate expression of Prx genes in the mandibular mesenchyme, we used the chick as a model system. We examined the patterns of gene expression in the face and the roles of signals derived from the epithelium on the expression of Prx genes in the mandibular mesenchyme. Our results demonstrated stage-dependent roles of mandibular epithelium on the expression of Prx in the mandibular mesenchyme and provide evidence for positive roles of members of the fibroblast and hedgehog families derived from mandibular epithelium on the expression of Prx genes in the mandibular mesenchyme. Our studies suggest that endothelin-1 signaling derived from the mesenchyme is involved in restricting the expression of Prx2 to the medial mandibular mesenchyme. PMID:18942149

  20. AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

    OpenAIRE

    Collino, Federica; Bruno, Stefania; Incarnato, Danny; Dettori, Daniela; Neri, Francesco; Provero, Paolo; Pomatto, Margherita; Oliviero, Salvatore; Tetta, Ciro; Quesenberry, Peter J.; Camussi, Giovanni

    2015-01-01

    Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stroma...

  1. Epithelial-mesenchymal transition in prostate cancer: an overview

    Science.gov (United States)

    Montanari, Micaela; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Malzone, Maria Gabriella; Vanacore, Daniela; Franco, Rossella Di; Mantia, Elvira La; Iovane, Gelsomina; Piscitelli, Raffaele; Muscariello, Raffaele; Berretta, Massimiliano; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Bianchi, Attilio Antonio Montano; Veneziani, Bianca Maria; Facchini, Gaetano

    2017-01-01

    Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer. Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance. In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance. PMID:28430640

  2. Isolation of mesenchymal stem cells from equine umbilical cord blood

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl

    2007-01-01

    . The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results: Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5o......Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low...

  3. The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming

    Directory of Open Access Journals (Sweden)

    Juli J. Unternaehrer

    2014-11-01

    Full Text Available Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs entails a mesenchymal to epithelial transition (MET. While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD of the epithelial-to-mesenchymal transition (EMT factor SNAI1 (SNAIL paradoxically reduced, while overexpression enhanced, reprogramming efficiency in human cells and in mouse cells, depending on strain. We observed nuclear localization of SNAI1 at an early stage of fibroblast reprogramming and using mouse fibroblasts expressing a knockin SNAI1-YFP reporter found cells expressing SNAI1 reprogrammed at higher efficiency. We further demonstrated that SNAI1 binds the let-7 promoter, which may play a role in reduced expression of let-7 microRNAs, enforced expression of which, early in the reprogramming process, compromises efficiency. Our data reveal an unexpected role for the EMT factor SNAI1 in reprogramming somatic cells to pluripotency.

  4. 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.

  5. Biology and clinical utilization of mesenchymal progenitor cells

    Directory of Open Access Journals (Sweden)

    J.J. Minguell

    2000-08-01

    Full Text Available Within the complex cellular arrangement found in the bone marrow stroma there exists a subset of nonhematopoietic cells referred to as mesenchymal progenitor cells (MPC. These cells can be expanded ex vivo and induced, either in vitro or in vivo, to terminally differentiate into at least seven types of cells: osteocytes, chondrocytes, adipocytes, tenocytes, myotubes, astrocytes and hematopoietic-supporting stroma. This broad multipotentiality, the feasibility to obtain MPC from bone marrow, cord and peripheral blood and their transplantability support the impact that the use of MPC will have in clinical settings. However, a number of fundamental questions about the cellular and molecular biology of MPC still need to be resolved before these cells can be used for safe and effective cell and gene therapies intended to replace, repair or enhance the physiological function of the mesenchymal and/or hematopoietic systems.

  6. 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...

  7. Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer.

    Science.gov (United States)

    Sciacovelli, Marco; Frezza, Christian

    2017-10-01

    Several lines of evidence indicate that during transformation epithelial cancer cells can acquire mesenchymal features via a process called epithelial-to-mesenchymal transition (EMT). This process endows cancer cells with increased invasive and migratory capacity, enabling tumour dissemination and metastasis. EMT is associated with a complex metabolic reprogramming, orchestrated by EMT transcription factors, which support the energy requirements of increased motility and growth in harsh environmental conditions. The discovery that mutations in metabolic genes such as FH, SDH and IDH activate EMT provided further evidence that EMT and metabolism are intertwined. In this review, we discuss the role of EMT in cancer and the underpinning metabolic reprogramming. We also put forward the hypothesis that, by altering chromatin structure and function, metabolic pathways engaged by EMT are necessary for its full activation. © 2017 Federation of European Biochemical Societies.

  8. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  9. Development of mesenchymal subtype gene signature for clinical application in gastric cancer.

    Science.gov (United States)

    Lee, Jeeyun; Cristescu, Razvan; Kim, Kyoung-Mee; Kim, Kyung; Kim, Seung Tae; Park, Se Hoon; Kang, Won Ki

    2017-09-12

    Previously, in the Asian Cancer Research Group (ACRG) project, we defined four distinct molecular subtypes in gastric cancer (GC). Mesenchymal (microsatellite stable with epithelial-to-mesenchymal transition phenotype, MSS/EMT) tumors showed the worst prognosis among all the subtypes. To develop a gene signature for predicting mesenchymal subtype GC, we conducted gene expression profiling using a NanoString assay in 70 ACRG specimens. The gene signature was validated in an independent set obtained from the prospective Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. The association between the mesenchymal subtype and survival was investigated. After cross-platform concordance test performed in 70 ACRG specimens, a 71-gene MSS/EMT signature was obtained. In the validation set, the gene signature predicted that 20 of 73 (27%) patients had mesenchymal tumors. Patients with mesenchymal subtype had diffuse GC, poorly-differentiated or signet ring cell carcinoma, and were microsatellite stable. The estimated hazard ratio for survival in patients with mesenchymal GC compared to those with non-mesenchymal tumors was 2.262 (95% confidence interval, 1.410 to 3.636; P=0.001). The survival difference remained significant when the subtypes were analyzed according to clinical prognostic parameters. This study suggested that the NanoString-based 71-gene signature for mesenchymal subtype is a strong predictor of the outcome in patients with GC.

  10. Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme.

    Science.gov (United States)

    Kim, Tae-Hee; Kim, Byeong-Moo; Mao, Junhao; Rowan, Sheldon; Shivdasani, Ramesh A

    2011-08-01

    The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are not fully characterized but include ligands of the Hedgehog (Hh) family, which originate in the epithelium and are necessary for mesenchymal cells to expand in number and drive elongation of the developing gut tube. The Notch signaling pathway has known requirements in fetal and adult intestinal epithelial progenitors. We detected Notch pathway activity in the embryonic gut mesenchyme and used conditional knockout mice to study its function. Selective disruption of the Notch effector gene RBP-Jκ (Rbpj) in the mesenchyme caused progressive loss of subepithelial fibroblasts and abbreviated gut length, revealing an unexpected requirement in this compartment. Surprisingly, constitutive Notch activity also induced rapid mesenchymal cell loss and impaired organogenesis, probably resulting from increased cell death and suggesting the need for a delicate balance in Notch signaling. Because digestive tract anomalies in mouse embryos with excess Notch activity phenocopy the absence of Hh signaling, we postulated that endodermal Hh restrains mesenchymal Notch pathway activity. Indeed, Hh-deficient embryos showed Notch overactivity in their defective gut mesenchyme and exposure to recombinant sonic hedgehog could override Notch-induced death of cultured fetal gut mesenchymal cells. These results reveal unexpected interactions between prominent signals in gastrointestinal development and provide a coherent explanation for Hh requirements in mesenchymal cell survival and organ growth.

  11. COUP-TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival.

    Science.gov (United States)

    Yu, Cheng-Tai; Tang, Ke; Suh, Jae Mi; Jiang, Rulang; Tsai, Sophia Y; Tsai, Ming-Jer

    2012-07-01

    Development of the metanephric kidney in mammals requires complex reciprocal tissue interactions between the ureteric epithelium and the mesenchyme. It is believed that Gdnf, produced in the metanephric mesenchyme, activates Ret signaling in the Wolffian duct to initiate the formation of the metanephros. However, the molecular mechanism for induction of Gdnf in the metanephric mesenchyme is not completely defined. Previous studies demonstrated that during the early stages of kidney development, loss of Osr1, Eya1, Pax2 or Wt1 gene function in the metanephric mesenchyme compromises the formation of the kidney. Moreover, it has been shown that the Hox11-Eya1-Pax2 complex activates the expression of Six2 and Gdnf in the metanephric mesenchyme to drive nephrogenesis. Here, we demonstrate that the orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII, also known as Nr2f2) is required for the specification of the metanephric mesenchyme. Deletion of COUP-TFII at E7.5 results in improper differentiation of the metanephric mesenchyme and absence of essential developmental regulators, such as Eya1, Six2, Pax2 and Gdnf. Importantly, we show that COUP-TFII directly regulates the expression of both Eya1 and Wt1 in the metanephric mesenchyme. Our findings reveal, for the first time, that COUP-TFII plays a central role in the specification of metanephric fate and in the maintenance of metanephric mesenchyme proliferation and survival by acting as a crucial regulator of Eya1 and Wt1 expression.

  12. Mesenchymal Stem Cell-Based Therapy for Prostate Cancer

    Science.gov (United States)

    2014-09-01

    Mesenchymal Stem Cell-Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs; Jeffrey Karp ...clinical trials for CRPC. The team is composed of Drs. Jeffrey Karp Co-Director of Regenerative Therapeutics at the Brigham & Women’s Hospital...encapsulating a PSA-activated thapsigargin-based prodrug (G115, Fig. 5) were generated by the Karp lab with the properties outlined in Table 7. These

  13. Induction of mesenchymal stem cell chondrogenesis by polyacrylate substrates

    OpenAIRE

    Glennon-Alty, Laurence; Williams, Rachel; Dixon, Simon; Murray, Patricia

    2013-01-01

    Mesenchymal stem cells (MSCs) can generate chondrocytes in vitro, but typically need to be cultured as aggregates in the presence of transforming growth factor beta (TGF-?), which makes scale-up difficult. Here we investigated if polyacrylate substrates modelled on the functional group composition and distribution of the Arg-Gly-Asp (RGD) integrin-binding site could induce MSCs to undergo chondrogenesis in the absence of exogenous TGF-?. Within a few days of culture on the biomimetic polyacry...

  14. The Alliance of Mesenchymal Stem Cells, Bone, and Diabetes

    Directory of Open Access Journals (Sweden)

    Nicola Napoli

    2014-01-01

    Full Text Available Bone fragility has emerged as a new complication of diabetes. Several mechanisms in diabetes may influence bone homeostasis by impairing the action between osteoblasts, osteoclasts, and osteocytes and/or changing the structural properties of the bone tissue. Some of these mechanisms can potentially alter the fate of mesenchymal stem cells, the initial precursor of the osteoblast. In this review, we describe the main factors that impair bone health in diabetic patients and their clinical impact.

  15. Colorectal Mesenchymal Tumor: A Clinicopathologic Study of 25 Cases

    Directory of Open Access Journals (Sweden)

    Chen-Hui Lee

    2005-07-01

    Conclusion: Two clinicopathologically different categories were identified from our colorectal mesenchymal tumors: intramural GISTs and polypoid submucosal leiomyomas. Our study suggests that GIST is a better categorization than smooth muscle tumor because of the malignant potential. Prognosis is strictly related to the number of mitoses. However, tumor size, nuclear atypia and tumor necrosis are probably also significant predictive factors of lethality. Future studies with DNA analysis and larger patient numbers are essential to evaluate the prognostic significance of our findings.

  16. Mesenchymal Stem Cells, Nanofiber Scaffolds and Ocular Surface Reconstruction

    Czech Academy of Sciences Publication Activity Database

    Holáň, Vladimír; Javorková, Eliška

    2013-01-01

    Roč. 9, č. 5 (2013), s. 609-619 ISSN 1550-8943 R&D Projects: GA ČR GAP304/11/0653; GA ČR(CZ) GAP301/11/1568 Grant - others:GA MŠk(CZ) UK668012; GA MŠk(CZ) SVV 265211 Institutional support: RVO:68378041 Keywords : mesenchymal stem cell s * limbal stem cell s * ocular surface injuries Subject RIV: EC - Immunology Impact factor: 3.214, year: 2013

  17. Mesenchymal Stem Cells: Emerging Therapy for Duchenne Muscular Dystrophy

    OpenAIRE

    Markert, Chad; Atala, Anthony; Cann, Jennifer K.; Christ, George; Furth, Mark; Ambrosio, Fabrisia; Childers, Martin K.

    2009-01-01

    Multipotent cells that can give rise to bone, cartilage, fat, connective tissue, skeletal and cardiac muscle are termed mesenchymal stem cells (MSCs). These cells were first identified in the bone marrow, distinct from blood-forming stem cells. Based on the embryologic derivation, availability, and various pro-regenerative characteristics, research exploring their use in cell therapy shows great promise for patients with degenerative muscle diseases and a number of other conditions. In this r...

  18. Human bone marrow-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Lopez M

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs have elicited a great clinical interest, particularly in the areas of regenerative medicine and induction of tolerance in allogeneic transplantation. Previous reports demonstrated the feasibility of transplanting MSCs, which generates new prospects in cellular therapy. Recently, injection of MSCs induced remission of steroid-resistant acute graft-versus-host disease (GVHD. This review summarizes the knowledge and possible future clinical uses of MSCs.

  19. MicroRNA Regulation of Epithelial to Mesenchymal Transition.

    Science.gov (United States)

    Abba, Mohammed L; Patil, Nitin; Leupold, Jörg Hendrik; Allgayer, Heike

    2016-01-14

    Epithelial to mesenchymal transition (EMT) is a central regulatory program that is similar in many aspects to several steps of embryonic morphogenesis. In addition to its physiological role in tissue repair and wound healing, EMT contributes to chemo resistance, metastatic dissemination and fibrosis, amongst others. Classically, the morphological change from epithelial to mesenchymal phenotype is characterized by the appearance or loss of a group of proteins which have come to be recognized as markers of the EMT process. As with all proteins, these molecules are controlled at the transcriptional and translational level by transcription factors and microRNAs, respectively. A group of developmental transcription factors form the backbone of the EMT cascade and a large body of evidence shows that microRNAs are heavily involved in the successful coordination of mesenchymal transformation and vice versa, either by suppressing the expression of different groups of transcription factors, or otherwise acting as their functional mediators in orchestrating EMT. This article dissects the contribution of microRNAs to EMT and analyzes the molecular basis for their roles in this cellular process. Here, we emphasize their interaction with core transcription factors like the zinc finger enhancer (E)-box binding homeobox (ZEB), Snail and Twist families as well as some pluripotency transcription factors.

  20. MicroRNA Regulation of Epithelial to Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Mohammed L. Abba

    2016-01-01

    Full Text Available Epithelial to mesenchymal transition (EMT is a central regulatory program that is similar in many aspects to several steps of embryonic morphogenesis. In addition to its physiological role in tissue repair and wound healing, EMT contributes to chemo resistance, metastatic dissemination and fibrosis, amongst others. Classically, the morphological change from epithelial to mesenchymal phenotype is characterized by the appearance or loss of a group of proteins which have come to be recognized as markers of the EMT process. As with all proteins, these molecules are controlled at the transcriptional and translational level by transcription factors and microRNAs, respectively. A group of developmental transcription factors form the backbone of the EMT cascade and a large body of evidence shows that microRNAs are heavily involved in the successful coordination of mesenchymal transformation and vice versa, either by suppressing the expression of different groups of transcription factors, or otherwise acting as their functional mediators in orchestrating EMT. This article dissects the contribution of microRNAs to EMT and analyzes the molecular basis for their roles in this cellular process. Here, we emphasize their interaction with core transcription factors like the zinc finger enhancer (E-box binding homeobox (ZEB, Snail and Twist families as well as some pluripotency transcription factors.

  1. Epithelial-mesenchymal transition in tissue repair and fibrosis.

    Science.gov (United States)

    Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

    2016-09-01

    The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

  2. Mechanism and regulation of epithelial–mesenchymal transition in cancer

    Directory of Open Access Journals (Sweden)

    Guttilla Reed IK

    2015-08-01

    Full Text Available Irene K Guttilla ReedDepartment of Biology, University of Saint Joseph, West Hartford, CT, USAAbstract: During development and the pathogenesis of certain diseases, including cancer, the epithelial–mesenchymal transition (EMT program is activated. It is hypothesized that EMT plays a major role in tumor invasion and the establishment of distant metastases. Metastatic disease is responsible for the vast majority of cancer-related deaths, which provides a precedent for elucidating pathways that regulate EMT. EMT is defined as the transition of cells with an epithelial phenotype into cells with a mesenchymal phenotype through a series of genetic and environmental events. This leads to the repression of epithelial-associated markers, upregulation of mesenchymal-associated markers, a loss of cell polarity and adhesion, and increased cell motility and invasiveness. EMT is a reversible and dynamic process, and can be regulated by signals from the microenvironment such as inflammation, hypoxia, and growth factors or epigenetically via microRNAs. These signals modulate key EMT-associated transcription factors and effector proteins that control cellular phenotype and regulate tumor plasticity in response to changing conditions in the microenvironment and the progressive nature of cancer. Understanding the complex regulatory networks controlling EMT can provide insight into tumor progression and metastasis.Keywords: EMT, metastasis, microRNA, transcription factor, growth factor, tumor progression

  3. Endothelial to mesenchymal transition in the cardiovascular system.

    Science.gov (United States)

    Gong, Hui; Lyu, Xing; Wang, Qiong; Hu, Min; Zhang, Xiangyu

    2017-09-01

    Endothelial to mesenchymal transition (EndMT) is a special type of epithelial to mesenchymal transition. It is a process that is characterized by the loss of features of endothelial cells and acquisition of specific markers of mesenchymal cells. A variety of stimuli, such as inflammation, growth factors, and hypoxia, regulate EndMT through various signaling pathways and intracellular transcription factors. It has been demonstrated that epigenetic modifications are also involved in this process. Recent studies have identified the essential role of EndMT in the cardiovascular system. EndMT contributes to steps in cardiovascular development, such as cardiac valve formation and septation, as well as the pathogenesis of various cardiovascular disorders, such as congenital heart disease, myocardial fibrosis, myocardial infarction and pulmonary arterial hypertension. Thus, comprehensive understanding of the underlying mechanisms of EndMT will provide novel therapeutic strategies to overcome congenital heart disease due to abnormal development and other cardiovascular diseases. This review will focus on summarizing the currently understood signaling pathways and epigenetic modifications involved in the regulation of EndMT and the role of EndMT in pathophysiological conditions of the cardiovascular system. Copyright © 2017. Published by Elsevier Inc.

  4. Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.

    Science.gov (United States)

    Goodnough, L Henry; Dinuoscio, Gregg J; Ferguson, James W; Williams, Trevor; Lang, Richard A; Atit, Radhika P

    2014-02-01

    The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

  5. Evidence for Kaposi Sarcoma Originating from Mesenchymal Stem Cell through KSHV-induced Mesenchymal-to-Endothelial Transition.

    Science.gov (United States)

    Li, Yuqing; Zhong, Canrong; Liu, Dawei; Yu, Wenjing; Chen, Weikang; Wang, Yan; Shi, Songtao; Yuan, Yan

    2018-01-01

    The major transmission route for Kaposi sarcoma-associated herpesvirus (KSHV) infection is the oral cavity through saliva. Kaposi sarcoma (KS) frequently occurs in the oral cavity in HIV-positive individuals and is often the first presenting sign of AIDS. However, the oral target cells for KSHV infection and the cellular origin of Kaposi sarcoma remain unknown. Here we present clinical and experimental evidences that Kaposi sarcoma spindle cells may originate from virally modified oral mesenchymal stem cells (MSC). AIDS-KS spindle cells expressed neuroectodermal stem cell marker (Nestin) and oral MSC marker CD29, suggesting an oral/craniofacial MSC lineage of AIDS-associated Kaposi sarcoma. Furthermore, oral MSCs were highly susceptible to KSHV infection, and infection promoted multilineage differentiation and mesenchymal-to-endothelial transition (MEndT). KSHV infection of oral MSCs resulted in expression of a large number of cytokines, a characteristic of Kaposi sarcoma, and upregulation of Kaposi sarcoma signature and MEndT-associated genes. These results suggest that Kaposi sarcoma may originate from pluripotent MSC and KSHV infection transforms MSC to Kaposi sarcoma-like cells through MEndT. Significance: These findings indicate that Kaposi sarcomas, which arise frequently in AIDS patients, originate from neural crest-derived mesenchymal stem cells, with possible implications for improving the clnical treatment of this malignancy. Cancer Res; 78(1); 230-45. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Human Thymus Mesenchymal Stromal Cells Augment Force Production in Self-Organized Cardiac Tissue

    Science.gov (United States)

    Sondergaard, Claus S.; Hodonsky, Chani J.; Khait, Luda; Shaw, John; Sarkar, Bedabrata; Birla, Ravi; Bove, Edward; Nolta, Jan; Si, Ming-Sing

    2011-01-01

    Background Mesenchymal stromal cells have been recently isolated from thymus gland tissue discarded after surgical procedures. The role of this novel cell type in heart regeneration has yet to be defined. The purpose of this study was to evaluate the therapeutic potential of human thymus-derived mesenchymal stromal cells using self-organized cardiac tissue as an in vitro platform for quantitative assessment. Methods Mesenchymal stromal cells were isolated from discarded thymus tissue from neonates undergoing heart surgery and were incubated in differentiation media to demonstrate multipotency. Neonatal rat cardiomyocytes self-organized into cardiac tissue fibers in a custom culture dish either alone or in combination with varying numbers of mesenchymal stromal cells. A transducer measured force generated by spontaneously contracting self-organized cardiac tissue fibers. Work and power outputs were calculated from force tracings. Immunofluorescence was performed to determine the fate of the thymus-derived mesenchymal stromal cells. Results Mesenchymal stromal cells were successfully isolated from discarded thymus tissue. After incubation in differentiation media, mesenchymal stromal cells attained the expected phenotypes. Although mesenchymal stromal cells did not differentiate into mature cardiomyocytes, addition of these cells increased the rate of fiber formation, force production, and work and power outputs. Self-organized cardiac tissue containing mesenchymal stromal cells acquired a defined microscopic architecture. Conclusions Discarded thymus tissue contains mesenchymal stromal cells, which can augment force production and work and power outputs of self-organized cardiac tissue fibers by several-fold. These findings indicate the potential utility of mesenchymal stromal cells in treating heart failure. PMID:20732499

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  7. GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma

    NARCIS (Netherlands)

    Moreno, Marta; Pedrosa, Leire; Pare, Laia; Pineda, Estela; Bejarano, Leire; Martinez, Josefina; Balasubramaniyan, Veerakumar; Ezhilarasan, Ravesanker; Kallarackal, Naveen; Kim, Sung-Hak; Wang, Jia; Audia, Alessandra; Conroy, Siobhan; Marin, Mercedes; Ribalta, Teresa; Pujol, Teresa; Herreros, Antoni; Tortosa, Avelina; Mira, Helena; Alonso, Marta M.; Gomez-Manzano, Candelaria; Graus, Francesc; Sulman, Erik P.; Piao, Xianhua; Nakano, Ichiro; Prat, Aleix; Bhat, Krishna P.; de la Iglesia, Nuria

    2017-01-01

    A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM) and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and

  8. Lung development requires an active ERK/MAPK pathway in the lung mesenchyme.

    Science.gov (United States)

    Boucherat, Olivier; Landry-Truchon, Kim; Aoidi, Rifdat; Houde, Nicolas; Nadeau, Valérie; Charron, Jean; Jeannotte, Lucie

    2017-01-01

    Reciprocal epithelial-mesenchymal communications are critical throughout lung development, dictating branching morphogenesis and cell specification. Numerous signaling molecules are involved in these interactions, but the way epithelial-mesenchymal crosstalk is coordinated remains unclear. The ERK/MAPK pathway transduces several important signals in lung formation. Epithelial inactivation of both Mek genes, encoding ERK/MAPK kinases, causes lung agenesis and death. Conversely, Mek mutation in mesenchyme results in lung hypoplasia, trachea cartilage malformations, kyphosis, omphalocele, and death. Considering the negative impact of kyphosis and omphalocele on intrathoracic space and, consequently, on lung growth, the exact role of ERK/MAPK pathway in lung mesenchyme remains unresolved. To address the role of the ERK/MAPK pathway in lung mesenchyme in absence of kyphosis and omphalocele, we used the Tbx4 Cre deleter mouse line, which acts specifically in lung mesenchyme. These Mek mutants did not develop kyphosis and omphalocele but they presented lung hypoplasia, tracheal defects, and neonatal death. Tracheal cartilage anomalies suggested a role for the ERK/MAPK pathway in the control of chondrocyte hypertrophy. Moreover, expression data indicated potential interactions between the ERK/MAPK and canonical Wnt pathways during lung formation. Lung development necessitates a functional ERK/MAPK pathway in the lung mesenchymal layer in order to coordinate efficient epithelial-mesenchymal interactions. Developmental Dynamics 246:72-82, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Mesodermal origin of median fin mesenchyme and tail muscle in amphibian larvae.

    Science.gov (United States)

    Taniguchi, Yuka; Kurth, Thomas; Medeiros, Daniel Meulemans; Tazaki, Akira; Ramm, Robert; Epperlein, Hans-Henning

    2015-06-18

    Mesenchyme is an embryonic precursor tissue that generates a range of structures in vertebrates including cartilage, bone, muscle, kidney, and the erythropoietic system. Mesenchyme originates from both mesoderm and the neural crest, an ectodermal cell population, via an epithelial to mesenchymal transition (EMT). Because ectodermal and mesodermal mesenchyme can form in close proximity and give rise to similar derivatives, the embryonic origin of many mesenchyme-derived tissues is still unclear. Recent work using genetic lineage tracing methods have upended classical ideas about the contributions of mesodermal mesenchyme and neural crest to particular structures. Using similar strategies in the Mexican axolotl (Ambystoma mexicanum), and the South African clawed toad (Xenopus laevis), we traced the origins of fin mesenchyme and tail muscle in amphibians. Here we present evidence that fin mesenchyme and striated tail muscle in both animals are derived solely from mesoderm and not from neural crest. In the context of recent work in zebrafish, our experiments suggest that trunk neural crest cells in the last common ancestor of tetrapods and ray-finned fish lacked the ability to form ectomesenchyme and its derivatives.

  10. [Effect of metanephric mesenchyme cells on podocytes apoptosis induced by high glucose].

    Science.gov (United States)

    Lü, Xin; Ren, Xiaojun; Yu, Weimin

    2016-05-10

    To study the effect of metanephric mesenchyme cells on podocytes apoptosis induced by high glucose. Mice's podocyte was cultured in vitro,and apoptosis and injury model of podocyte was then established by high glucose (30 mmol/L) induction. Metanephric mesenchyme cells were extracted from E13.5 mouse embryos and used to make conditioned medium which was used to treat podocytes apoptosis. The flow cytometry and confocal fluorescence imaging were used to detect the apoptosis ratio and cytoskeletal protein (synaptopodin) expression of podocyte at several time points (24, 48, 72 h), in order to explore the effect of high glucose on podocytes and the treatment effect of metanephric mesenchyme cell conditioned medium. Significant increasing of podocyte apoptosis ratio and decreasing in synaptopodin expression contrast to control group was observed after induction of high glucose, with a statistical difference. Metanephric mesenchyme cells could be isolated from E13.5 mouse embryos successfully, and had the capacity of osteogenic and adipogenic differentiation. Metanephric mesenchyme cell conditioned medium and high glucose stimulations was used to generate podocytes cells. Compared to the group treated with high glucose stimulation, the flow cytometry detection result suggested that metanephric mesenchyme cell could reduce podocytes apoptosis in a dose-dependent manner: with increasing in the concentration of metanephric mesenchyme cell conditioned medium, the treatment effect was better. Metanephric mesenchyme cells could prevent apoptosis and injury of podocyte induced by high glucose.

  11. In vitro and in vivo neurogenic potential of mesenchymal stem cells ...

    Indian Academy of Sciences (India)

    Keywords. Clinical trials; mesenchymal stem cells (MSCs); neuronal differentiation; self-renewal. Abstract. Regenerative medicine is an evolving interdisciplinary topic of research involving numerous technological methods that utilize stem cells to repair damaged tissues. Particularly, mesenchymal stem cells (MSCs) are a ...

  12. Morphological and immunohistochemical identification of epithelial-to-mesenchymal transition in clinical prostate cancer

    NARCIS (Netherlands)

    K. Kolijn (Kimberley); E.I. Verhoef (Esther); G.J.H.L. Leenders (Geert)

    2015-01-01

    textabstractEpithelial-to-mesenchymal transition (EMT) is a process known to be associated with aggressive tumor behavior, metastasis and treatment resistance. It is characterized by coincidental upregulation of mesenchymal markers such as vimentin, fibronectin and N-cadherin concurrent with

  13. Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Giovanna Calabrese

    2015-07-01

    Full Text Available The Low-Affinity Nerve Growth Factor Receptor (LNGFR, also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271+ and CD271− mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271+ and CD271− mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. Compared to CD271+, CD271− mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271+ mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271+ mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.

  14. Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation.

    Science.gov (United States)

    Calabrese, Giovanna; Giuffrida, Raffaella; Lo Furno, Debora; Parrinello, Nunziatina Laura; Forte, Stefano; Gulino, Rosario; Colarossi, Cristina; Schinocca, Luciana Rita; Giuffrida, Rosario; Cardile, Venera; Memeo, Lorenzo

    2015-07-09

    The Low-Affinity Nerve Growth Factor Receptor (LNGFR), also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271+ and CD271- mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271+ and CD271- mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. Compared to CD271+, CD271- mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271+ mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271+ mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.

  15. Molecular and environmental cues in cardiac differentiation of mesenchymal stem cells

    NARCIS (Netherlands)

    Ramkisoensing, Arti Anushka

    2014-01-01

    In this thesis molecular and environmental cues in cardiac differentiation of mesenchymal stem cells were investigated. The main conclusions were that the cardiac differentiation potential of human mesenchymal stem cells negatively correlates with donor age. This in its own shows a negative

  16. Design and development of a magnetic device for mesenchymal stem cell retaining in deep targets

    Science.gov (United States)

    Banis, G. C.

    2017-12-01

    This paper focuses on the retaining of mesenchymal stem cells in blood flow conditions using the appropriate magnetic field. Mesenchymal stem cells can be tagged with magnetic nanoparticles and thus, they can be manipulated from distance, through the application of an external magnetic field. In this paper the case of kidney as target of the therapy is being studied.

  17. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation.

    Science.gov (United States)

    Zhou, Ya-Jing; Liu, Jian-Min; Wei, Shu-Ming; Zhang, Yun-Hao; Qu, Zhen-Hua; Chen, Shu-Bo

    2015-08-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  18. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    DEFF Research Database (Denmark)

    Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn

    2001-01-01

    . It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells......The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated......, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer...

  19. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Science.gov (United States)

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats. PMID:26487860

  20. Immunosuppressive and remodelling properties of mesenchymal stem cells in a model of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Patricia Semedo

    2009-12-01

    Full Text Available Objective: To investigate the role of mesenchymal stem cells in fibrogenesis using a model of chronic renal insufficiency. Methods: Mesenchymal stem cells  were obtained from tibias and femurs of Wistar-EPM rats. After three to five passages, the cells were submitted to phenotypic analyses and differentiation. Wistar rats were submitted to the 5/6 nephrectomy model, and 2.105 mesenchymal stem cells  were administered intravenously to each rat every two weeks until the eighth week. Rresults: Sex-determining region Y was observed in female rats treated with stem cells. Serum and urine analyses showed improvement of functional parameters in mesenchymal stem cells treated animals, such as creatinine, serum urea, and proteinuria. Moreover, hemocrit analysis showed improvement of anemia in mesenchymal stem cells treated animals. Masson’s Trichromium and Picrosirius Red staining demonstrated reduced levels of fibrosis in mesenchymal stem cells treated in animals. These results were corroborated by reduced vimentin, collagen I, TGFβ, FSP-1, MCP-1 and Smad3 mRNA expression. Renal IL-6 and TNFα mRNA expression levels were significantly decreased after mesenchymal stem cells treatment, while IL-4 and IL-10 expression were increased. Serum expression of IL-1α, IL-1β, IL-6, IFN-γ, TNF-α, and IL-10 was decreased in mesenchymal cell-treated animals. Cconclusions: Altogether, these results suggest that mesenchymal stem cells therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal lesion. The immunosuppresive and remodeling properties of the mesenchymal stem cells  may be involved in the improved fibrotic outcome.

  1. Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme.

    Science.gov (United States)

    Hiremath, Minoti; Dann, Pamela; Fischer, Jennifer; Butterworth, Daniela; Boras-Granic, Kata; Hens, Julie; Van Houten, Joshua; Shi, Wei; Wysolmerski, John

    2012-11-01

    Parathyroid hormone-related protein (PTHrP) regulates cell fate and specifies the mammary mesenchyme during embryonic development. Loss of PTHrP or its receptor (Pthr1) abolishes the expression of mammary mesenchyme markers and allows mammary bud cells to revert to an epidermal fate. By contrast, overexpression of PTHrP in basal keratinocytes induces inappropriate differentiation of the ventral epidermis into nipple-like skin and is accompanied by ectopic expression of Lef1, β-catenin and other markers of the mammary mesenchyme. In this study, we document that PTHrP modulates Wnt/β-catenin signaling in the mammary mesenchyme using a Wnt signaling reporter, TOPGAL-C. Reporter expression is completely abolished by loss of PTHrP signaling and ectopic reporter activity is induced by overexpression of PTHrP. We also demonstrate that loss of Lef1, a key component of the Wnt pathway, attenuates the PTHrP-induced abnormal differentiation of the ventral skin. To characterize further the contribution of canonical Wnt signaling to embryonic mammary development, we deleted β-catenin specifically in the mammary mesenchyme. Loss of mesenchymal β-catenin abolished expression of the TOPGAL-C reporter and resulted in mammary buds with reduced expression of mammary mesenchyme markers and impaired sexual dimorphism. It also prevented the ectopic, ventral expression of mammary mesenchyme markers caused by overexpression of PTHrP in basal keratinocytes. Therefore, we conclude that a mesenchymal, canonical Wnt pathway mediates the PTHrP-dependent specification of the mammary mesenchyme.

  2. Mesenchymal dental pulp cells attenuate dentin resorption in homeostasis.

    Science.gov (United States)

    Zheng, Y; Chen, M; He, L; Marão, H F; Sun, D M; Zhou, J; Kim, S G; Song, S; Wang, S L; Mao, J J

    2015-06-01

    Dentin in permanent teeth rarely undergoes resorption in development, homeostasis, or aging, in contrast to bone that undergoes periodic resorption/remodeling. The authors hypothesized that cells in the mesenchymal compartment of dental pulp attenuate osteoclastogenesis. Mononucleated and adherent cells from donor-matched rat dental pulp (dental pulp cells [DPCs]) and alveolar bone (alveolar bone cells [ABCs]) were isolated and separately cocultured with primary rat splenocytes. Primary splenocytes readily aggregated and formed osteoclast-like cells in chemically defined osteoclastogenesis medium with 20 ng/mL of macrophage colony-stimulating factor (M-CSF) and 50 ng/mL of receptor activator of nuclear factor κB ligand (RANKL). Strikingly, DPCs attenuated osteoclastogenesis when cocultured with primary splenocytes, whereas ABCs slightly but significantly promoted osteoclastogenesis. DPCs yielded ~20-fold lower RANKL expression but >2-fold higher osteoprotegerin (OPG) expression than donor-matched ABCs, yielding a RANKL/OPG ratio of 41:1 (ABCs:DPCs). Vitamin D3 significantly promoted RANKL expression in ABCs and OPG in DPCs. In vivo, rat maxillary incisors were atraumatically extracted (without any tooth fractures), followed by retrograde pulpectomy to remove DPCs and immediate replantation into the extraction sockets to allow repopulation of the surgically treated root canal with periodontal and alveolar bone-derived cells. After 8 wk, multiple dentin/root resorption lacunae were present in root dentin with robust RANKL and OPG expression. There were areas of dentin resoprtion alternating with areas of osteodentin formation in root dentin surface in the observed 8 wk. These findings suggest that DPCs of the mesenchymal compartment have an innate ability to attenuate osteoclastogenesis and that this innate ability may be responsible for the absence of dentin resorption in homeostasis. Mesenchymal attenuation of dentin resorption may have implications in internal

  3. Systems biology of facial development: contributions of ectoderm and mesenchyme.

    Science.gov (United States)

    Hooper, Joan E; Feng, Weiguo; Li, Hong; Leach, Sonia M; Phang, Tzulip; Siska, Charlotte; Jones, Kenneth L; Spritz, Richard A; Hunter, Lawrence E; Williams, Trevor

    2017-06-01

    The rapid increase in gene-centric biological knowledge coupled with analytic approaches for genomewide data integration provides an opportunity to develop systems-level understanding of facial development. Experimental analyses have demonstrated the importance of signaling between the surface ectoderm and the underlying mesenchyme are coordinating facial patterning. However, current transcriptome data from the developing vertebrate face is dominated by the mesenchymal component, and the contributions of the ectoderm are not easily identified. We have generated transcriptome datasets from critical periods of mouse face formation that enable gene expression to be analyzed with respect to time, prominence, and tissue layer. Notably, by separating the ectoderm and mesenchyme we considerably improved the sensitivity compared to data obtained from whole prominences, with more genes detected over a wider dynamic range. From these data we generated a detailed description of ectoderm-specific developmental programs, including pan-ectodermal programs, prominence- specific programs and their temporal dynamics. The genes and pathways represented in these programs provide mechanistic insights into several aspects of ectodermal development. We also used these data to identify co-expression modules specific to facial development. We then used 14 co-expression modules enriched for genes involved in orofacial clefts to make specific mechanistic predictions about genes involved in tongue specification, in nasal process patterning and in jaw development. Our multidimensional gene expression dataset is a unique resource for systems analysis of the developing face; our co-expression modules are a resource for predicting functions of poorly annotated genes, or for predicting roles for genes that have yet to be studied in the context of facial development; and our analytic approaches provide a paradigm for analysis of other complex developmental programs. Copyright © 2017 Elsevier Inc

  4. Organotypic three-dimensional culture model of mesenchymal ...

    Science.gov (United States)

    Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling pathways elucidated using gene knockout mouse models. A broad analysis of literature, ToxRefDB, and ToxCast identified 63 chemicals that are related to cleft palate. However,the influence of these putative teratogens on human palatal fusion has not been studied due to the lack of in vitro models. We sought to engineer the stratified mesenchymal and epithelial structure of the developing palate in vitro via organotypic culture of human mesenchymal stem cell (hMSC) spheroids coated with a single layer of human primary epidermalkeratinocytes (hPEKp). hMSC spheroids exhibited uniform size over time (175 ± 21 µm mean diameter) proportional to starting cell density. Further, we developed a novel procedure to coat hMSC spheroids homogeneously with a single layer of hPEKp cells using a seeding ratio of 0.1-0.2 hPEKp per hMSC, and hMSC/hPEKp spheroids expressed mesenchymal markers (vim+, C044+, CD105+, CD34-) and epithelial markers (krt17+, itga6+) via qRT-PCR. Analysis of adverse outcome pathways related to palate fusion points to an EGF/TGFj33 switch that could be a target for cleft palate teratogens, and both egf and egfr were expressed by hMSC/hPEKp spheres. Finally, hMSCs and hPE

  5. Potential uses for cord blood mesenchymal stem cells.

    Science.gov (United States)

    Zarrabi, Morteza; Mousavi, Seyed Hadi; Abroun, Saeid; Sadeghi, Bahareh

    2014-01-01

    Stem cell therapy is a powerful technique for the treatment of a number of diseases. Stem cells are derived from different tissue sources, the most important of which are the bone marrow (BM), umbilical cord (UC) blood and liver. Human UC mesenchymal stem cells (hUC-MSCs) are multipotent, non-hematopoietic stem cells that have the ability to self-renew and differentiate into other cells and tissues such as osteoblasts, adipocytes and chondroblasts. In a number of reports, human and mouse models of disease have hUC-MSCs treatments. In this article, we review studies that pertain to the use of hUC-MSCs as treatment for diseases.

  6. Epithelial to mesenchymal transition in human endocrine islet cells.

    Directory of Open Access Journals (Sweden)

    José Luis Moreno-Amador

    Full Text Available β-cells undergo an epithelial to mesenchymal transition (EMT when expanded in monolayer culture and give rise to highly proliferative mesenchymal cells that retain the potential to re-differentiate into insulin-producing cells.To investigate whether EMT takes place in the endocrine non-β cells of human islets.Human islets isolated from 12 multiorgan donors were dissociated into single cells, purified by magnetic cell sorting, and cultured in monolayer.Co-expression of insulin and the mesenchymal marker vimentin was identified within the first passage (p1 and increased subsequently (insulin+vimentin+ 7.2±6% at p1; 43±15% at p4. The endocrine non-β-cells did also co-express vimentin (glucagon+vimentin+ 59±1.5% and 93±6%, somatostatin+vimentin+ 16±9.4% and 90±10% at p1 and p4 respectively; PP+vimentin+ 74±14% at p1; 88±12% at p2. The percentage of cells expressing only endocrine markers was progressively reduced (0.6±0.2% insulin+, 0.2±0.1% glucagon+, and 0.3±0.2% somatostatin+ cells at p4, and 0.7±0.3% PP+ cells at p2. Changes in gene expression were also indicated of EMT, with reduced expression of endocrine markers and the epithelial marker CDH-1 (p<0.01, and increased expression of mesenchymal markers (CDH-2, SNAI2, ZEB1, ZEB2, VIM, NT5E and ACTA2; p<0.05. Treatment with the EMT inhibitor A83-01 significantly reduced the percentage of co-expressing cells and preserved the expression of endocrine markers.In adult human islets, all four endocrine islet cell types undergo EMT when islet cells are expanded in monolayer conditions. The presence of EMT in all islet endocrine cells could be relevant to design of strategies aiming to re-differentiate the expanded islet cells towards a β-cell phenotype.

  7. Isolation of Mesenchymal Stem Cells from Adipose Tissue

    OpenAIRE

    Islam, Andi Asadul

    2015-01-01

    BACKGROUND: In searching for the best source of stem cells, researcher found adipose stem cells as one of the ideal source due to its easiness in harvesting and its potential for differentiating into other cell lineage. METHODS: We isolated stem cells from adipose tissue, cultured and confirmed its immunophenotype using polymerase chain reaction. RESULTS: Cluster of differentiation (CD)44, CD73, CD90, CD105 were expressed, which represent immunophenotype of mesenchymal stem cells.  CONCLUSION...

  8. Importance of mesenchymal stem cells in autologous fat grafting

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter Viktor

    2012-01-01

    the fat graft with adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We have reviewed original studies published on fat transplantation enriched with ASC. We found four murine and three human studies that investigated the subject after a sensitive search of publications....... In the human studies, so-called cell assisted lipotransfer (CAL) increased the ASC concentration 2-5 times compared with non-manipulated fat grafts, which caused a questionable improvement in survival of fat grafts, compared with that of traditional lipofilling. In contrast, in two of the murine studies ASC...

  9. Proptosis Caused by Rhabdomyomatous Mesenchymal Hamartomata Occurring in the Orbit.

    Science.gov (United States)

    Phan, Isabella T; Courtney, R Jackson; Marx, Douglas P; Wilson, David J; Mansoor, Atiya; Ng, John D

    2016-01-01

    Two infants were referred for progressive orbital proptosis. MRI in both cases demonstrated a homogenous mass in the orbit adherent to and isointense with a rectus muscle. Histopathology in both cases demonstrated a bland proliferation of spindle cells with entrapped skeletal muscle. Immunochemistry demonstrated that the abnormal tissue was of skeletal muscle origin, consistent with rhabdomyomatous mesenchymal hamartoma (RMH). Observation was elected due to the reported benign nature of RMH. In contrast to RMH of the cutaneous tissues that typically follows a benign course, RMH of the orbit may present with rapid growth.

  10. Mesenchymal stem cells in diabetes treatment: progress and perspectives

    Directory of Open Access Journals (Sweden)

    Yu CHENG

    2016-08-01

    Full Text Available Diabetes is a chronic metabolic disorder caused by relative or absolute insulin deficient or reduced sensitivity of target cells to insulin. Mesenchymal stem cells (MSCs are adult stem cells with multiple differentiation potential, self-renewable and immunoregulatory properties. Accumulating evidences from clinic or animal experiments recent years showed that MSCs infusion could ameliorate hyperglycemia in diabetes. The research progress of MSCs in diabetes treatment is summarized and a corresponding perspective is herewith proposed in present paper. DOI: 10.11855/j.issn.0577-7402.2016.07.16

  11. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  12. Epithelial-mesenchymal transition: An emerging target in tissue fibrosis

    Science.gov (United States)

    Li, Meirong; Luan, Fuxin; Zhao, Yali; Hao, Haojie; Zhou, Yong; Han, Weidong

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT-related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis. PMID:26361988

  13. Applications of Mesenchymal Stem Cells in Oral and Craniofacial Regeneration.

    Science.gov (United States)

    Shakoori, Pasha; Zhang, Quanzhou; Le, Anh D

    2017-02-01

    The field of tissue engineering and regenerative medicine has been rapidly expanded through multidisciplinary integration of research and clinical practice in response to unmet clinical needs for reconstruction of dental, oral, and craniofacial structures. The significance of the various types of stem cells, specifically mesenchymal stem cells derived from the orofacial tissues, ranging from dental pulp stem cells to periodontal ligament stem cells to mucosa/gingiva has been thoroughly investigated and their applications in tissue regeneration are outlined in this article. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    2006-12-01

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  15. Mesenchymal stromal cell therapy in ischemic heart disease

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja Dam; Ali Qayyum, Abbas

    2016-01-01

    is very costly for the health care system. Therefore, new treatment options and strategies are being researched intensely. Stem cell therapy to improve myocardial perfusion and stimulate growth of new cardiomyocytes could be a new way to go. Nevertheless, the results from clinical studies have varied...... considerably, probably due to the use of many different cell lines obtained from different tissues and the different patient populations. The present review will focus on treatment with the mesenchymal stromal cell from bone marrow and adipose tissue in animal and patients with acute and chronic IHD (CIHD)....

  16. Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Christensen, Rikke; Sørensen, Flemming Brandt

    2011-01-01

    better understanding and in vivo supporting data. The homing ability of hMSCs was investigated by creating a human xenograft model by transplanting an ovarian cancer cell line into immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were injected through the tail vein......The field of stem cell biology continues to evolve by characterization of further types of stem cells and by exploring their therapeutic potential for experimental and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the most promising candidates simply because...

  17. The mechanosensor of mesenchymal stem cells: mechanosensitive channel or cytoskeleton?

    Science.gov (United States)

    Xiao, E; Chen, Chider; Zhang, Yi

    2016-09-20

    Mesenchymal stem cells (MSCs) are multipotent adult stem cells. MSCs and their potential for use in regenerative medicine have been investigated extensively. Recently, the mechanisms by which MSCs detect mechanical stimuli have been described in detail. As in other cell types, both mechanosensitive channels, such as transient receptor potential melastatin 7 (TRPM7), and the cytoskeleton, including actin and actomyosin, have been implicated in mechanosensation in MSCs. This review will focus on discussing the precise role of TRPM7 and the cytoskeleton in mechanosensation in MSCs.

  18. Osteosarcoma of breast: A rare case of extraskeletal osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ashwin A Kallianpur

    2013-01-01

    Full Text Available Primary osteogenic sarcomas of the breast are exceptionally uncommon. We describe such a case occurring in a 50 year-old woman who presented with a large painful mass in her left breast. Simple mastectomy of the left breast was performed. Microscopical and immunohistochemical findings established the diagnosis of primary osteogenic sarcoma. Similar to extremity osteosarcoma, adjuvant adriamycin and cisplatin based chemotherapy and external beam radiotherapy was given to the present case. She remained well 57 months later, without tumor recurrence. The current article made a literature search proving the rarity of this lesion type and discusses in detail the diagnostic implications and the treatment of this rare site tumor entity.

  19. Extra-skeletal Ewing's sarcoma resembling acute abdomen. Case report.

    Science.gov (United States)

    Valdivia Gómez, Gilberto Guzmán; Soto Guerrero, María Teresa; Cedillo de la Cruz, María Isabel

    2010-01-01

    Extraosseous Ewing's sarcoma is a rare tumor of neuroectodermal origin. It presents mainly in the soft tissue of the extremities and thorax. Histologically, it is similar to Ewing's sarcoma of the bone. We present the case of a male who arrived at the emergency room with acute abdomen, leucocytosis and imaging techniques (abdominal ultrasound and computed tomography) suggestive of complicated diverticular disease. He was treated with emergency surgery. Intraoperative findings were an unsuspected tumor (20 x 15 x 15 cm). Treatment consisted of extirpation of the tumor, separating it from the adjacent viscera and followed by chemotherapy based on epirubicin, cyclophosphamide and vincristine for six cycles. Because the control abdominal CT demonstrated tumor activity in the retroperitoneum adjacent to the ascending colon and cecum, further resection was decided upon. In a review of the literature, no previous reports of extraosseous Ewing's sarcoma were found presenting as acute abdomen. Due to the rarity of this tumor, only case reports or series have been found in the literature without randomized or comparative studies. Surgery was the cornerstone of treatment, without reports of preoperative chemotherapy. If the patient's condition permits, percutaneous needle biopsy is mandatory to obtain optimum treatment as well as to improve prognosis.

  20. Extraskeletal osteogenic sarcoma after treatment for Wilms' tumor

    International Nuclear Information System (INIS)

    Belasco, J.B.; Meadows, A.T.; Chatten, J.; Borden, S.; Schnaufer, L.

    1982-01-01

    A large proportion of children with Wilms' tumor will become long-term disease-free survivors. A small number of these children are at risk of developing second malignant neoplasms. There have been no previous reports of osteogenic sarcoma of the chest wall following treatment of Wilms' tumor. Our patient was age seven years when he received surgery, radiation therapy and chemotherapy for Wilms' tumor, eight years when he received radiation and chemotherapy for pulmonary metastases of Wilms' tumor, and 13 years when he developed osteogenic sarcoma of the chest wall

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

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    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.

  2. Mesenchymal stem cell in venous leg ulcer: An intoxicating therapy.

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    Athanerey, Anjali; Patra, Pradeep Kumar; Kumar, Awanish

    2017-08-01

    Venous leg ulcers (VLU) are a prevalent and reoccurring type of complicated wound, turning as a considerable public healthcare issue, with critical social and economic concern. There are both medical and surgical therapies to treat venous leg ulcers; however, a cure does not yet exist. Mesenchymal stem cells (MSC) are capable and proved of accelerating wound healing in vivo and their study with human chronic wounds is currently awaited. MSCs are a promising source of adult progenitor cells for cellular therapy and have been demonstrated to differentiate into various mesenchymal cell lineages. They have a crucial and integral role in native wound healing by regulating immune response and inflammation. Improved understanding of the cellular and molecular mechanisms at work in delayed wound healing compels to the development of cellular therapy in VLU. This review focuses on the current treatment option of VLU and further emphasizing the role of MSCs in accelerating the healing process. With further understanding of the mechanism of action of these cells in wound improvement and, the involvement of cytokines can also be revealed that could be used for the therapeutic purpose for VLU healing. Clinical uses of MSCs have been started already, and induced MSCs are surely a promising tool or compelling therapy for VLU. Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  3. Induction of mesenchymal stem cell chondrogenesis by polyacrylate substrates.

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    Glennon-Alty, Laurence; Williams, Rachel; Dixon, Simon; Murray, Patricia

    2013-04-01

    Mesenchymal stem cells (MSCs) can generate chondrocytes in vitro, but typically need to be cultured as aggregates in the presence of transforming growth factor beta (TGF-β), which makes scale-up difficult. Here we investigated if polyacrylate substrates modelled on the functional group composition and distribution of the Arg-Gly-Asp (RGD) integrin-binding site could induce MSCs to undergo chondrogenesis in the absence of exogenous TGF-β. Within a few days of culture on the biomimetic polyacrylates, both mouse and human MSCs, and a mesenchymal-like mouse-kidney-derived stem cell line, began to form multi-layered aggregates and started to express the chondrocyte-specific markers, Sox9, collagen II and aggrecan. Moreover, collagen II tended to be expressed in the centre of the aggregates, similarly to developing limb buds in vivo. Surface analysis of the substrates indicated that those with the highest surface amine content were most effective at promoting MSC chondrogenesis. These results highlight the importance of surface group functionality and the distribution of those groups in the design of substrates to induce MSC chondrogenesis. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells.

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    Masahiro Kondo

    Full Text Available OBJECTIVE: Mesenchymal stem cells (MSCs can differentiate into cells of mesenchymal lineages, such as osteoblasts and chondrocytes. Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs. METHODS: Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression. RESULTS: Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA, which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis. CONCLUSIONS: IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation.

  5. Epithelial-to-mesenchymal transition in the development of endometriosis.

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    Yang, Yan-Meng; Yang, Wan-Xi

    2017-06-20

    Endometriosis, an estrogen-dependent chronic gynecological disease, is common in reproductive-age women and profoundly affects their life quality. Although various pathogenic theories have been proposed, the origin of endometriosis remains unclear. Epithelial to mesenchymal transition (EMT) is a process that epithelial cells lose polarized organization of the cytoskeleton and cell-to-cell contacts, acquiring the high motility of mesenchymal cells. These changes are thought to be prerequisites for the original establishment of endometriotic lesions. However, no study exactly indicates which type of EMT occurs in endometriosis. In this review, we conclude that two different types of EMT may participate in this disease. Besides, two stimulating signals, hypoxia and estrogen, can through different pathways to activate the EMT process in endometriosis. Those pathways involve many cellular factors such as TGF-beta and Wnt, ultimately leading to cell proliferation and migration. As infertility is becoming a serious and intractable issue for women, EMT, during the implantation process, is gaining attention. In this review, we will describe the known functions of EMT in endometriosis, and suggest further studies that may aid in the development of medical therapy.

  6. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

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    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  7. Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine

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    Devang M. Patel

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expanded in vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases.

  8. Establishment of mesenchymal cell line derived from human developing odontoma.

    Science.gov (United States)

    Hatano, H; Kudo, Y; Ogawa, I; Shimasue, H; Shigeishi, H; Ohta, K; Higashikawa, K; Takechi, M; Takata, T; Kamata, N

    2012-11-01

    An odontoma, which shows proliferating odontogenic epithelium and mesenchymal tissue, is one of the most common odontogenic tumors encountered. These are commonly found in tooth-bearing regions, although the etiology remains unknown. There are no previous reports of an established line of immortalized human odontoma cells. Using odontoma fragments obtained from a girl treated at our department, we established an immortalized human odontoma cell line and investigated cell morphology, dynamic proliferation, the presence of contamination, and karyotype. Moreover, cell characterization was examined using osteogenic and odontogenic markers. We successfully established a mesenchymal odontoma cell (mOd cells). The cells were found to be fibroblastic and had a high level of telomerase activity. Cell growth was confirmed after more than 200 population doublings without significant growth retardation. mOd cells expressed mRNA for differentiation markers, including collagen type I (COLI), alkaline phosphatase, bone sialoprotein, osteopontin, osteocalcin, cementum-derived protein (CP-23), dentin sialophosphoprotein (DSPP), and distal-less homeobox 3 (DLX3), as well as bone morphogenetic proteins (BMPs). In addition, they showed a high level of calcified nodule formation activity in vitro. We successfully established a cell line that may be useful for investigating the mechanisms of normal odontogenesis as well as characteristics of odontoma tumors. © 2012 John Wiley & Sons A/S.

  9. Multilineage Potential Research of Bovine Amniotic Fluid Mesenchymal Stem Cells

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    Yuhua Gao

    2014-02-01

    Full Text Available The use of amnion and amniotic fluid (AF are abundant sources of mesenchymal stem cells (MSCs that can be harvested at low cost and do not pose ethical conflicts. In human and veterinary research, stem cells derived from these tissues are promising candidates for disease treatment, specifically for their plasticity, their reduced immunogenicity, and high anti-inflammatory potential. This work aimed to obtain and characterize bovine amniotic fluid mesenchymal stem cells (AFMSC. The bovine AF from the amniotic cavity of pregnant gilts in the early stages of gestation (3- and 4-m-old bovine embryos was collected. AFMSCs exhibit a fibroblastic-like morphology only starting from the fourth passage, being heterogeneous during the primary culture. Immunofluorescence results showed that AFMSCs were positive for β-integrin, CD44, CD73 and CD166, but negative for CD34, CD45. Meanwhile, AFMSCs expressed ES cell markers, such as Oct4, and when appropriately induced, are capable of differentiating into ectodermal and mesodermal lineages. This study reinforces the emerging importance of these cells as ideal tools in veterinary medicine; future studies aimed at a deeper evaluation of their immunological properties will allow a better understanding of their role in cellular therapy.

  10. Epithelial to Mesenchymal Transition in a Clinical Perspective

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    Jennifer Pasquier

    2015-01-01

    Full Text Available Tumor growth and metastatic dissemination rely on cellular plasticity. Among the different phenotypes acquired by cancer cells, epithelial to mesenchymal transition (EMT has been extensively illustrated. Indeed, this transition allows an epithelial polarized cell to acquire a more mesenchymal phenotype with increased mobility and invasiveness. The role of EMT is quite clear during developmental stage. In the neoplastic context in many tumors EMT has been associated with a more aggressive tumor phenotype including local invasion and distant metastasis. EMT allows the cell to invade surrounding tissues and survive in the general circulation and through a stem cell phenotype grown in the host organ. The molecular pathways underlying EMT have also been clearly defined and their description is beyond the scope of this review. Here we will summarize and analyze the attempts made to block EMT in the therapeutic context. Indeed, till today, most of the studies are made in animal models. Few clinical trials are ongoing with no obvious benefits of EMT inhibitors yet. We point out the limitations of EMT targeting such tumor heterogeneity or the dynamics of EMT during disease progression.

  11. Glucosamine-Based Supramolecular Nanotubes for Human Mesenchymal Cell Therapy.

    Science.gov (United States)

    Talloj, Satish Kumar; Cheng, Bill; Weng, Jen-Po; Lin, Hsin-Chieh

    2018-04-23

    Herein, we demonstrate an example of glucosamine-based supramolecular hydrogels that can be used for human mesenchymal cell therapy. We designed and synthesized a series of amino acid derivatives based on a strategy of capping d-glucosamine moiety at the C-terminus and fluorinated benzyl group at the N-terminus. From a systematic study on chemical structures, we discovered that the glucosamine-based supramolecular hydrogel [pentafluorobenzyl (PFB)-F-Glu] self-assembled with one-dimensional nanotubular structures at physiological pH. The self-assembly of a newly discovered PFB-F-Glu motif is attributed to the synergistic effect of π-π stacking and extensive intermolecular hydrogen bonding network in aqueous medium. Notably, PFB-F-Glu nanotubes are proven to be nontoxic to human mesenchymal stem cells (hMSCs) and have been shown to enhance hMSC proliferation while maintaining their pluripotency. Retaining of pluripotency capabilities provides potentially unlimited source of undifferentiated cells for the treatment of future cell therapies. Furthermore, hMSCs cultured on PFB-F-Glu are able to secrete paracrine factors that downregulate profibrotic gene expression in lipopolysaccharide-treated human skin fibroblasts, which demonstrates that PFB-F-Glu nanotubes have the potential to be used for wound healing applications. Overall, this article addresses the importance of chemical design to generate supramolecular biomaterials for stem cell therapy.

  12. Mesenchymal stem cell and osteoarthritis: a literature review

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    Zhaleh Shariati Sarabi

    2016-04-01

    Full Text Available The most common disease in the aged population is osteoarthritis (OA that is resulting in progressive dysfunction following isolated cartilage injuries, subchondral bone remodeling, tissue loss, marginal osteophytes, and loss of joint space. Mesenchymal stem cells (MSCs are multipotent stem cells; they are able to produce many or all joint tissues. Bone marrow and adipose tissue are rich sources of mesenchymal cells that are useful for the reconstruction of injured tissues such as bone, cartilage, or cardiac muscle. Recently, some studies have been performed on the use of the direct intra-articular injection of mononuclear cells (MNCs and MSCs as potential therapeutic targets in OA. In this review, the history of MSCs in the treatment of OA are explained. Injection of Bone Marrow Aspirates Concentrate (BMAC has significantly improved both joint pain and function in radiologic findings; some studies suggested that the injection would be even more effective in early to moderate phases of OA. Injection of MSCs in combination with growth factors may be better solution for the treatment.

  13. Mesenchymal stem cells for cartilage repair in osteoarthritis.

    Science.gov (United States)

    Gupta, Pawan K; Das, Anjan K; Chullikana, Anoop; Majumdar, Anish S

    2012-07-09

    Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA.

  14. Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes.

    Science.gov (United States)

    Bruna, Flavia; Contador, David; Conget, Paulette; Erranz, Benjamín; Sossa, Claudia L; Arango-Rodríguez, Martha L

    2016-01-01

    Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult's BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult's BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.

  15. Implications of mesenchymal stem cells in regenerative medicine.

    Science.gov (United States)

    Kariminekoo, Saber; Movassaghpour, Aliakbar; Rahimzadeh, Amirbahman; Talebi, Mehdi; Shamsasenjan, Karim; Akbarzadeh, Abolfazl

    2016-05-01

    Mesenchymal stem cells (MSCs) are a population of multipotent progenitors which reside in bone marrow, fat, and some other tissues and can be isolated from various adult and fetal tissues. Self-renewal potential and multipotency are MSC's hallmarks. They have the capacity of proliferation and differentiation into a variety of cell lineages like osteoblasts, condrocytes, adipocytes, fibroblasts, cardiomyocytes. MSCs can be identified by expression of some surface molecules like CD73, CD90, CD105, and lack of hematopoietic specific markers including CD34, CD45, and HLA-DR. They are hopeful tools for regenerative medicine for repairing injured tissues. Many studies have focused on two significant features of MSC therapy: (I) systemically administered MSCs home to sites of ischemia or injury, and (II) MSCs can modulate T-cell-mediated immunological responses. MSCs express chemokine receptors and ligands involved in cells migration and homing process. MSCs induce immunomedulatory effects on the innate (dendritic cells, monocyte, natural killer cells, and neutrophils) and the adaptive immune system cells (T helper-1, cytotoxic T lymphocyte, and B lymphocyte) by secreting soluble factors like TGF-β, IL-10, IDO, PGE-2, sHLA-G5, or by cell-cell interaction. In this review, we discuss the main applications of mesenchymal stem in Regenerative Medicine and known mechanisms of homing and Immunomodulation of MSCs.

  16. Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes

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    Flavia Bruna

    2016-01-01

    Full Text Available Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult’s BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult’s BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.

  17. Isolation of mesenchymal stem cells from human vermiform appendix.

    Science.gov (United States)

    De Coppi, Paolo; Pozzobon, Michela; Piccoli, Martina; Gazzola, Maria Vittoria; Boldrin, Luisa; Slanzi, Elisa; Destro, Roberta; Zanesco, Luigi; Zanon, Giovanni Franco; Gamba, Piergiorgio

    2006-09-01

    Recent findings have shown that pluripotent stem cells exist in areas outside the bone marrow (BM). Moreover, it has been demonstrated that the appendix is important for the development of mucosal gut immunity, and hematopoietic progenitors have been isolated from animal and human appendices. Non-inflamed appendices removed during laparotomy were processed and cultured until the appearance of adherent cells. Differentiations (performed under osteogenic, adipogenic, and myogenic conditions) were confirmed by immunohistochemistry and cytochemistry. Polymerase chain reaction and cytofluorimetric analyses were performed to evidence the presence of genes and protein specific lineages in appendix-derived mesenchymal stem cells (ADMCs). ADMCs were present in non-inflamed appendices. ADMCs under osteogenic conditions differentiated in osteoblasts and showed increased alkaline phosphatase expression; at the gene level, we observed the expression of Core binding factor alpha 1 (Cbfa1) and osteocalcin in osteogenic induced ADMCs. Under adipogenic conditions, lipidic drops in the cytoplasm, expression of lipoprotein lipase (LpL), and peroxisome proliferator-activated receptor gamma were observed; under myogenic conditions, myotubes expressing muscle specific proteins like desmin were formed. Myogenic regulatory factor 4 and MyoD were selectively induced in the ADMCs under myogenic conditions. This study shows for the first time that mesenchymal stem cells can be isolated from normal appendices obtained from a pediatric and adult age group (0-18 years of age). This finding not only may further knowledge of the maturation of the intestinal immunesystem but also could indicate a new physiological role of the human vermiform appendix.

  18. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

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    Hongshan Liu

    Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

  19. Starfish ApDOCK protein essentially functions in larval defense system operated by mesenchyme cells.

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    Furukawa, Ryohei; Funabashi, Hiromi; Matsumoto, Midori; Kaneko, Hiroyuki

    2012-11-01

    In larvae of the starfish, Asterina pectinifera, mesenchyme cells operate in the defense system through various behaviors. We have investigated mesenchyme cell dynamics during the immune response by identifying ApDOCK, a new member of the DOCK180 superfamily protein. In 4-day-old bipinnaria larvae processed for morpholino oligonucleotide-mediated knockdown of ApDOCK, injection of inorganic foreign substances revealed that (1) mesenchyme cells fail to undergo either directed migration toward a large oil-droplet or persistent spreading on the oil-droplet after contact; (2) neither uptake of micro-beads nor cell-to-cell fusion on the large oil-droplet differed from that of mesenchyme cells from control larvae. Similar behaviors were also recorded in experiments where bacteria were injected. Under culture conditions, the expression level of ApDOCK mRNA was significantly associated with the immunological behavior of mesenchyme cells. Apparently, the mesenchyme cells from ApDOCK loss-of-function larvae exhibited insufficient lamellipodium formation via lack of fibrous form of actin organization at the leading edge. These results suggest that the migratory congregation and persistence of encapsulation of larval mesenchyme cells are intracellularly regulated by ApDOCK protein, and this regulation is associated with organization of cytoskeletal actin.

  20. An explant assay for assessing cellular behavior of the cranial mesenchyme.

    Science.gov (United States)

    Sarkar, Anjali A; Zohn, Irene E

    2013-01-20

    The central nervous system is derived from the neural plate that undergoes a series of complex morphogenetic movements resulting in formation of the neural tube in a process known as neurulation. During neurulation, morphogenesis of the mesenchyme that underlies the neural plate is believed to drive neural fold elevation. The cranial mesenchyme is comprised of the paraxial mesoderm and neural crest cells. The cells of the cranial mesenchyme form a pourous meshwork composed of stellate shaped cells and intermingling extracellular matrix (ECM) strands that support the neural folds. During neurulation, the cranial mesenchyme undergoes stereotypical rearrangements resulting in its expansion and these movements are believed to provide a driving force for neural fold elevation. However, the pathways and cellular behaviors that drive cranial mesenchyme morphogenesis remain poorly studied. Interactions between the ECM and the cells of the cranial mesenchyme underly these cell behaviors. Here we describe a simple ex vivo explant assay devised to characterize the behaviors of these cells. This assay is amendable to pharmacological manipulations to dissect the signaling pathways involved and live imaging analyses to further characterize the behavior of these cells. We present a representative experiment demonstrating the utility of this assay in characterizing the migratory properties of the cranial mesenchyme on a variety of ECM components.

  1. Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis.

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    Hayashi, Toru; Lombaert, Isabelle M A; Hauser, Belinda R; Patel, Vaishali N; Hoffman, Matthew P

    2017-01-09

    Epithelial-mesenchymal interactions involve fundamental communication between tissues during organogenesis and are primarily regulated by growth factors and extracellular matrix. It is unclear whether RNA-containing exosomes are mobile genetic signals regulating epithelial-mesenchymal interactions. Here we identify that exosomes loaded with mesenchyme-specific mature microRNA contribute mobile genetic signals from mesenchyme to epithelium. The mature mesenchymal miR-133b-3p, loaded into exosomes, was transported from mesenchyme to the salivary epithelium, which did not express primary miR-133b-3p. Knockdown of miR-133b-3p in culture decreased endbud morphogenesis, reduced proliferation of epithelial KIT + progenitors, and increased expression of a target gene, Disco-interacting protein 2 homolog B (Dip2b). DIP2B, which is involved in DNA methylation, was localized with 5-methylcytosine in the prophase nucleus of a subset of KIT + progenitors during mitosis. In summary, exosomal transport of miR-133b-3p from mesenchyme to epithelium decreases DIP2B, which may function as an epigenetic regulator of genes responsible for KIT + progenitor expansion during organogenesis. Published by Elsevier Inc.

  2. Myogenic differentiation of mesenchymal stem cells for muscle regeneration in urinary tract.

    Science.gov (United States)

    Yang, Bin; Zheng, Jun-hua; Zhang, Yuan-yuan

    2013-01-01

    This article was to review the current status of adult mesenchymal stem cells transplantation for muscle regeneration in urinary tract and propose the future prospect in this field. The data used in this review were mainly obtained from articles listed in Medline and PubMed (2000-2013). The search terms were "mesenchymal stem cells", "bladder", "stress urinary incontinence" and "tissue engineering". Articles regarding the adult mesenchymal stem cells for tissue engineering of bladder and stress urinary incontinence were selected and reviewed. Adult mesenchymal stem cells had been identified and well characterized in human bone marrow, adipose tissue, skeletal muscle and urine, and demonstrated the capability of differentiating into smooth muscle cells and skeletal muscle cells under myogenic differentiation conditions in vitro. Multiple preclinical and clinical studies indicated that adult mesenchymal stem cells could restore and maintain the structure and function of urinary muscle tissues after transplanted, and potentially improve the quality of life in patients. Smooth or skeletal myogenic differentiation of mesenchymal stem cells with regenerative medicine technology may provide a novel approach for muscle regeneration and tissue repair in urinary tract. The long-term effect and safety of mesenchymal stem cell transplantation should be further evaluated before this approach becomes widely used in patients.

  3. Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

    Science.gov (United States)

    Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

    2018-01-01

    Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

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

    Science.gov (United States)

    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

  5. Form follows function: Morphological and immunohistological insights into epithelial-mesenchymal transition characteristics of tumor buds.

    Science.gov (United States)

    Enderle-Ammour, Kathrin; Bader, Moritz; Ahrens, Theresa Dorothee; Franke, Kai; Timme, Sylvia; Csanadi, Agnes; Hoeppner, Jens; Kulemann, Birte; Maurer, Jochen; Reiss, Philip; Schilling, Oliver; Keck, Tobias; Brabletz, Thomas; Stickeler, Elmar; Werner, Martin; Wellner, Ulrich Friedrich; Bronsert, Peter

    2017-05-01

    In cancer biology, the architectural concept "form follows function" is reflected by cell morphology, migration, and epithelial-mesenchymal transition protein pattern. In vivo, features of epithelial-mesenchymal transition have been associated with tumor budding, which correlates significantly with patient outcome. Hereby, the majority of tumor buds are not truly detached but still connected to a major tumor mass. For detailed insights into the different tumor bud types and the process of tumor budding, we quantified tumor cells according to histomorphological and immunohistological epithelial-mesenchymal transition characteristics. Three-dimensional reconstruction from adenocarcinomas (pancreatic, colorectal, lung, and ductal breast cancers) was performed as published. Tumor cell morphology and epithelial-mesenchymal transition characteristics (represented by zinc finger E-box-binding homeobox 1 and E-Cadherin) were analyzed qualitatively and quantitatively in a three-dimensional context. Tumor buds were classified into main tumor mass, connected tumor bud, and isolated tumor bud. Cell morphology and epithelial-mesenchymal transition marker expression were assessed for each tumor cell. Epithelial-mesenchymal transition characteristics between isolated tumor bud and connected tumor bud demonstrated no significant differences or trends. Tumor cell count correlated significantly with epithelial-mesenchymal transition and histomorphological characteristics. Regression curve analysis revealed initially a loss of membranous E-Cadherin, followed by expression of cytoplasmic E-Cadherin and subsequent expression of nuclear zinc finger E-box-binding homeobox 1. Morphologic changes followed later in this sequence. Our data demonstrate that connected and isolated tumor buds are equal concerning immunohistochemical epithelial-mesenchymal transition characteristics and histomorphology. Our data also give an insight in the process of tumor budding. While there is a notion that

  6. Breast cancer normalization induced by embryonic mesenchyme is mediated by extracellular matrix biglycan.

    Science.gov (United States)

    Bischof, Ashley G; Yüksel, Deniz; Mammoto, Tadanori; Mammoto, Akiko; Krause, Silva; Ingber, Donald E

    2013-08-01

    Some epithelial cancers can be induced to revert to quiescent differentiated tissue when combined with embryonic mesenchyme; however, the mechanism of this induction is unknown. Here we combine tissue engineering, developmental biology, biochemistry and proteomics approaches to attack this problem. Using a synthetic reconstitution system, we show that co-culture of breast cancer cells with embryonic mesenchyme from early stage (E12.5-13.5) mammary glands decreases tumor cell proliferation while stimulating acinus differentiation, whereas cancer-associated fibroblasts (CAFs) fail to produce these normalizing effects. When insoluble extracellular matrices (ECMs) were isolated from cultured early stage (E12.5-13.5) embryonic mammary mesenchyme cells or E10 tooth mesenchyme and recombined with mammary tumor cells, they were found to be sufficient to induce breast cancer normalization including enhanced expression of estrogen receptor-α (ER-α). In contrast, ECM from later stage (E14.5) mammary mesenchyme and conditioned medium isolated from mesenchymal cell cultures were ineffective. Importantly, when the inductive ECMs produced by early stage embryonic mammary mesenchyme were scraped from dishes and injected into fast-growing breast tumors in mice, they significantly inhibited cancer expansion. Proteomics analysis of the detergent insoluble ECM material revealed several matrix components that were preferentially expressed in the embryonic ECMs. Analysis of two of these molecules previously implicated in cancer regulation--biglycan and tenascin C--revealed that addition of biglyan can mimic the tumor normalization response, and that siRNA knockdown of its expression in cultured embryonic mesenchyme results in loss of the ECM's inductive activity. These studies confirm that embryonic mesenchyme retains the ability to induce partial breast cancer reversion, and that its inductive capability resides at least in part in the ECM protein biglycan that it produces.

  7. Does the cranial mesenchyme contribute to neural fold elevation during neurulation?

    Science.gov (United States)

    Zohn, Irene E; Sarkar, Anjali A

    2012-10-01

    The central nervous system is derived from the neural plate, which undergoes a series of complex morphogenetic events resulting in formation of the neural tube in a process known as neurulation. The cellular behaviors driving neurulation in the cranial region involve forces generated by the neural tissue itself as well as the surrounding epithelium and mesenchyme. Of interest, the cranial mesenchyme underlying the neural plate undergoes stereotypical rearrangements hypothesized to drive elevation of the neural folds. As the neural folds rise, the hyaluronate-rich extracellular matrix greatly expands resulting in increased space between individual cranial mesenchyme cells. Based on inhibitor studies, expansion of the extracellular matrix has been implicated in driving neural fold elevation; however, because the surrounding neural and epidermal ectoderm were also affected by inhibitor exposure, these studies are inconclusive. Similarly, treatment of neurulating embryos with teratogenic doses of retinoic acid results in altered organization of the cranial mesenchyme, but alterations in surrounding tissues are also observed. The strongest evidence for a critical role for the cranial mesenchyme in neural fold elevation comes from studies of genes expressed exclusively in the cranial mesenchyme that when mutated result in exencephaly associated with abnormal organization of the cranial mesenchyme. Twist is the best studied of these and is expressed in both the paraxial mesoderm and neural crest derived cranial mesenchyme. In this article, we review the evidence implicating the cranial mesenchyme in providing a driving force for neural fold elevation to evaluate whether there are sufficient data to support this hypothesis. Copyright © 2012 Wiley Periodicals, Inc.

  8. Mesenchymal hamartoma of the liver demonstrating peripheral calcification in a 12-year-old boy

    International Nuclear Information System (INIS)

    Steiner, Michael A.; Giles, Henry W.

    2008-01-01

    Mesenchymal hamartoma of the liver is a rare benign hepatic tumor that typically presents in the first 2 years of life. Approximately 85% of affected children present before the age of 3 years and less than 5% present after the age of 5 years. Although spontaneous regression has been reported in this benign tumor, most mesenchymal hamartomas gradually increase in size and can reach enormous proportions. We present an atypical case of mesenchymal hamartoma in a 12-year-old boy. The boy's age and presence of calcifications on CT demonstrate a unique presentation of this rare entity. (orig.)

  9. Role of fibronectin in primary mesenchyme cell migration in the sea urchin

    OpenAIRE

    1985-01-01

    We studied the effect of fibronectin (FN) on the behavior of primary mesenchyme cells isolated from sea urchin mesenchyme blastulae in vitro using a time-lapse technique. The migration of isolated primary mesenchyme cells reconstituted in seawater and horse serum is dependent on the presence or absence of exogenous FN in the culture media. The cells in FN, 4 and 40 micrograms/ml, show a high percentage of migration and migrate long distances, whereas a higher concentration of FN at 400 microg...

  10. Isolation of Multipotent Mesenchymal Stromal Cells from Cryopreserved Human Umbilical Cord Tissue.

    Science.gov (United States)

    Romanov, Yu A; Balashova, E E; Volgina, N E; Kabaeva, N V; Dugina, T N; Sukhikh, G T

    2016-02-01

    Umbilical cord stroma is an easily available, convenient, and promising source of multipotent mesenchymal stromal cells for regenerative medicine. Cryogenic storage of umbilical cord tissue provides more possibilities for further isolation of multipotent mesenchymal stromal cells for autologous transplantation or scientific purposes. Here we developed a protocol for preparation of the whole umbilical cord tissue for cryogenic storage that in combination with the previously described modified method of isolation of multipotent mesenchymal stromal cells allowed us to isolate cells with high proliferative potential, typical phenotype, and preserved differentiation potencies.

  11. Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Paul H van der Horst

    Full Text Available BACKGROUND: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs as well as progesterone receptor (PR positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT. METHODOLOGY AND PRINCIPAL FINDINGS: Paraffin sections from patients with (n = 9 or without (n = 9 progressive endometrial cancer (recurrent or metastatic disease were assessed for the presence of CD4+ (helper, CD8+ (cytotoxic and Foxp3+ (regulatory T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK endometrial cancer cell lines stably transfected with PRA (IKPRA, PRB (IKPRB and PRA+PRB (IKPRAB were cultured in presence/absence of progesterone (MPA and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signaling. CONCLUSION: Intact progesterone signaling in non

  12. MicroRNA expression in a phosphaturic mesenchymal tumour

    Directory of Open Access Journals (Sweden)

    Darrell Green

    2017-12-01

    Full Text Available Phosphaturic mesenchymal tumours are a heterogeneous set of bone and soft tissue neoplasms that can cause a number of paraneoplastic syndromes such as tumour induced osteomalacia. The term phosphaturic comes from the common finding that these tumours secrete high levels of fibroblast growth factor 23 which causes renal phosphate wasting leading to hypophosphatemia. Phosphaturic mesenchymal tumours are rare and diagnosis is difficult. A very active 68 year old male presented with bone pain and muscle weakness. He was hypophosphataemic and total alkaline phosphatase was markedly elevated. The patient was placed on vitamin D supplementation but his condition progressed. In the fifth year of presentation the patient required the use of a wheelchair and described “explosive” bone pain on physical contact. Serum 1,25 dihydroxyvitamin D was low and serum fibroblast growth factor 23 was significantly elevated, raising suspicion of a phosphaturic mesenchymal tumour. A lesion was detected in his left femoral head and the patient underwent a total hip replacement. The patient displayed a rapid improvement to his condition and during a three year follow up period he returned to an active lifestyle. As molecular testing may help provide a robust diagnosis and is particularly useful in rare diseases we took a next generation sequencing approach to identify a differential expression of small RNAs in the resected tumour. Small RNAs are non-coding RNA molecules that play a key role in regulation of gene expression and can be used as specific biomarkers. We found an upregulation of miR-197. We also found a downregulation of miR-20b, miR-144 and miR-335 which is a small RNA profile typical of osteosarcoma. MiR-21, the most frequently upregulated microRNA in cancer, was downregulated. We conclude that the specific small RNA profile is typical of osteosarcoma except for the downregulation of oncogenic miR-21. Transcriptional plasticity of miR-197, which is

  13. Imaging gene expression in human mesenchymal stem cells: from small to large animals

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Paulmurugan, Ramasamy; Rodriguez-Porcel, Martin

    2009-01-01

    To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning....

  14. Unique CCT repeats mediate transcription of the TWIST1 gene in mesenchymal cell lines

    International Nuclear Information System (INIS)

    Ohkuma, Mizue; Funato, Noriko; Higashihori, Norihisa; Murakami, Masanori; Ohyama, Kimie; Nakamura, Masataka

    2007-01-01

    TWIST1, a basic helix-loop-helix transcription factor, plays critical roles in embryo development, cancer metastasis and mesenchymal progenitor differentiation. Little is known about transcriptional regulation of TWIST1 expression. Here we identified DNA sequences responsible for TWIST1 expression in mesenchymal lineage cell lines. Reporter assays with TWIST1 promoter mutants defined the -102 to -74 sequences that are essential for TWIST1 expression in human and mouse mesenchymal cell lines. Tandem repeats of CCT, but not putative CREB and NF-κB sites in the sequences substantially supported activity of the TWIST1 promoter. Electrophoretic mobility shift assay demonstrated that the DNA sequences with the CCT repeats formed complexes with nuclear factors, containing, at least, Sp1 and Sp3. These results suggest critical implication of the CCT repeats in association with Sp1 and Sp3 factors in sustaining expression of the TWIST1 gene in mesenchymal cells

  15. Lentiviral-Mediated Transgene Expression Can Potentiate Intestinal Mesenchymal-Epithelial Signaling

    Directory of Open Access Journals (Sweden)

    Dismuke Adria D

    2009-07-01

    Full Text Available Abstract Mesenchymal-epithelial signaling is essential for the development of many organs and is often disrupted in disease. In this study, we demonstrate the use of lentiviral-mediated transgene delivery as an effective approach for ectopic transgene expression and an alternative to generation of transgenic animals. One benefit to this approach is that it can be used independently or in conjunction with established transgenic or knockout animals for studying modulation of mesenchymal-epithelial interactions. To display the power of this approach, we explored ectopic expression of a Wnt ligand in the mouse intestinal mesenchyme and demonstrate its functional influence on the adjacent epithelium. Our findings highlight the efficient use of lentiviral-mediated transgene expression for modulating mesenchymal-epithelial interactions in vivo.

  16. 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...... a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during...

  17. Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

    DEFF Research Database (Denmark)

    Haack-Sorensen, M.; Friis, T.; Bindslev, L.

    2008-01-01

    OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under...

  18. Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs

    DEFF Research Database (Denmark)

    Rowe, R.G.; Li, X.Y.; Hu, Y.

    2009-01-01

    Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis....... Whether Snail1 also regulates the behavior of terminally differentiated mesenchymal cells remains unexplored. Using a Snai1 conditional knockout model, we now identify Snail1 as a regulator of normal mesenchymal cell function. Snail1 expression in normal fibroblasts can be induced by agonists known...... to promote proliferation and invasion in vivo. When challenged within a tissue-like, three-dimensional extracellular matrix, Snail1-deficient fibroblasts exhibit global alterations in gene expression, which include defects in membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive activity...

  19. Absence of maternal cell contamination in mesenchymal stromal cell cultures derived from equine umbilical cord tissue

    Czech Academy of Sciences Publication Activity Database

    Vacková, Irena; Czerneková, V.; Tománek, M.; Navrátil, J.; Moško, Tibor; Nováková, Z.

    2014-01-01

    Roč. 35, č. 8 (2014), s. 655-657 ISSN 0143-4004 Institutional support: RVO:68378041 Keywords : maternal cell contamination * mesenchymal stromal cells * umbilical cord tissue Subject RIV: FH - Neurology Impact factor: 2.710, year: 2014

  20. Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology

    NARCIS (Netherlands)

    Scharstuhl, A.; Schewe, B.; Benz, K.; Gaissmaier, C.; Bühring, H.J.; Stoop, R.

    2007-01-01

    Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from

  1. Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology.

    NARCIS (Netherlands)

    Scharstuhl, A.; Schewe, B.; Benz, K.; Gaissmaier, C.; Buhring, H.J.; Stoop, R.

    2007-01-01

    Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from

  2. Lentiviral-Mediated Transgene Expression Can Potentiate Intestinal Mesenchymal-Epithelial Signaling

    Directory of Open Access Journals (Sweden)

    Kohn Aimee

    2009-01-01

    Full Text Available Abstract Mesenchymal-epithelial signaling is essential for the development of many organs and is often disrupted in disease. In this study, we demonstrate the use of lentiviral-mediated transgene delivery as an effective approach for ectopic transgene expression and an alternative to generation of transgenic animals. One benefit to this approach is that it can be used independently or in conjunction with established transgenic or knockout animals for studying modulation of mesenchymal-epithelial interactions. To display the power of this approach, we explored ectopic expression of a Wnt ligand in the mouse intestinal mesenchyme and demonstrate its functional influence on the adjacent epithelium. Our findings highlight the efficient use of lentiviral-mediated transgene expression for modulating mesenchymal-epithelial interactions in vivo.

  3. The effects of X-irradiation on the chondrogensis of mesenchymal cells

    International Nuclear Information System (INIS)

    Ha, Jong Ryeol

    2002-01-01

    It is well known that X-irradiation affects on maturing process of differentiated chondrocytes. Nevertheless, It has been remained elusively whether X-irradiation affects the process of differentiation of mesenchymal cells which differentiate into chondrocyte, fibroblast, or muscle cells. In this study, we examined the effect of X-irradiation (with 1 to 10 Gy) on chondrogenesis using mesenchymal cells of chick limb bud. Our results show that X-irradiation dose-dependently inhibited chondrogenesis. This result suggests that immature chondroblast-like mesenchymal cells are sensitive to X-irradiation, Moreover, X-irradiation affects not only maturing process of chondrocytes, but also inhibits the chondrogenesis. Taken together, we demonstrate that the whole process of differentiation of mature chondrocytes from mesenchymal cells is affected by X-irradiation and undifferentiated cells were more affected by X-irradiation than mature cells

  4. Roles of hesC and gcm in echinoid larval mesenchyme cell development.

    Science.gov (United States)

    Yamazaki, Atsuko; Minokawa, Takuya

    2016-04-01

    To understand the roles of hesC and gcm during larval mesenchyme specification and differentiation in echinoids, we performed perturbation experiments for these genes in two distantly related euechinoids, Hemicentrotus pulcherrimus and Scaphechinus mirabilis. The number of larval mesenchyme cells increased when the translation of hesC was inhibited, thereby suggesting that hesC has a general role in larval mesenchyme development. We confirmed previous results by demonstrating that gcm is involved in pigment cell differentiation. Simultaneous inhibition of the translation of hesC and gcm induced a significant increase in the number of skeletogenic cells, which suggests that gcm functions in skeletogenic fate repression. Based on these observations, we suggest that: (i) hesC participates in some general aspects of mesenchymal cell development; and (ii) gcm is involved in the mechanism responsible for the binary specification of skeletogenic and pigment cell fates. © 2016 Japanese Society of Developmental Biologists.

  5. Role of cell-matrix contacts in cell migration and epithelial-mesenchymal transformation.

    Science.gov (United States)

    Hay, E D

    1990-12-02

    Epithelial cells make contact with extracellular matrix via receptors on the basal surface that interact with the basal actin cortex. In 3D matrix, the mesenchymal cell makes contact with matrix all around its circumference via similar receptors. When moving, the fibroblasts is constantly constructing a new front end. We postulate in a 'fixed cortex' theory of cell motility that the circumferential actin cortex is firmly attached to matrix and that the myosin-rich endoplasm slides past it into the continually forming new front end. During epithelial-mesenchymal transformation, the presumptive mesenchymal cell seems to turn on the new front end mechanism as a way of emigrating from the epithelium into the underlying matrix with which it makes 'fixed' contacts. Master genes may exist that regulate the expression of epithelial genes on the one hand, and mesenchymal genes on the other.

  6. Extrahepatic biliary cystadenoma with mesenchymal stroma: a true biliary cystadenoma? A case report.

    LENUS (Irish Health Repository)

    Hennessey, Derek B

    2012-02-01

    Biliary cystadenomas are benign but potentially malignant cystic neoplasms, which classically contain mesenchymal stroma similar to ovarian tissue. We report a case of an extra-hepatic biliary cystadenoma with mesenchymal stroma along with a discussion of current pathological opinion. CASE PRESENTATION: A 54-year-old female presented with abdominal pain, abnormal liver function tests and a mass on ultrasound. Computerized Tomography identified a complex multi-locular cyst in the common hepatic duct. Radical excision of the lesion and a Roux-en-Y loop bilio-enteric anastomosis was performed. Histology confirmed the presence of a benign biliary cystadenoma with ovarian type stroma. CONCLUSION: Biliary cystadenomas classically contain mesenchymal stroma similar to ovarian tissue. It now appears that cystadenomas without mesenchymal stroma appear to be more akin to similar cystic lesions of the pancreas, and may represent a dissimilar neoplasm. Therefore, malignant transformation can occur, so complete excision is recommended.

  7. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation

    Science.gov (United States)

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption. PMID:27068606

  8. Optimized Protocol for Isolation of Multipotent Mesenchymal Stromal Cells from Human Umbilical Cord.

    Science.gov (United States)

    Romanov, Yu A; Balashova, E E; Volgina, N E; Kabaeva, N V; Dugina, T N; Sukhikh, G T

    2015-11-01

    Extraembryonic tissues, in particular, umbilical cord stroma are promising sources of multipotent mesenchymal stromal cells for regenerative medicine. In recent years, methods for isolation of mesenchymal stromal cells from different compartments of the umbilical cords based on enzymatic disaggregation of the tissue or on tissue explants have been proposed. Here we propose a protocol of isolation of multipotent mesenchymal stromal cells from the whole umbilical cord that combines the advantages of each approach and ensures sufficient cell yield for further experimental and clinical applications. A combination of short-term incubation of tissue fragments on cold collagenase solution followed by their culturing in the form of explants significantly increased the yield of cells with high proliferative activity, typical pluripotent mesenchymal stromal cell phenotype, and preserved differentiation capacity.

  9. Expanded cryopreserved mesenchymal stromal cells as an optimal source for graft-versus-host disease treatment

    Czech Academy of Sciences Publication Activity Database

    Holubová, M.; Lysák, D.; Vlas, T.; Vannucci, Luca; Jindra, P.

    2014-01-01

    Roč. 42, č. 3 (2014), s. 139-144 ISSN 1045-1056 Institutional support: RVO:61388971 Keywords : Mesenchymal stromal cells * Cryopreservation * Immunomodulation Subject RIV: EC - Immunology Impact factor: 1.209, year: 2014

  10. Mesenchymal stem cell therapy: Two steps forward, one step back

    Science.gov (United States)

    Ankrum, James; Karp, Jeffrey M.

    2010-01-01

    Mesenchymal stem cell (MSC) therapy is poised to establish a new clinical paradigm; however, recent trials have produced mixed results. Although MSC were originally considered to treat connective tissue defects, preclinical studies revealed potent immunomodulatory properties that prompted the use of MSC to treat numerous inflammatory conditions. Unfortunately, although clinical trials have met safety endpoints, efficacy has not been demonstrated. We believe the challenge to demonstrate efficacy can be attributed in part to an incomplete understanding of the fate of MSC following infusion. Here, we highlight the clinical status of MSC therapy and discuss the importance of cell-tracking techniques, which have advanced our understanding of the fate and function of systemically infused MSC and might improve clinical application. PMID:20335067

  11. Osteogenic differentiation of human dental papilla mesenchymal cells

    International Nuclear Information System (INIS)

    Ikeda, Etsuko; Hirose, Motohiro; Kotobuki, Noriko; Shimaoka, Hideki; Tadokoro, Mika; Maeda, Masahiko; Hayashi, Yoshiko; Kirita, Tadaaki; Ohgushi, Hajime

    2006-01-01

    We isolated dental papilla from impacted human molar and proliferated adherent fibroblastic cells after collagenase treatment of the papilla. The cells were negative for hematopoietic markers but positive for CD29, CD44, CD90, CD105, and CD166. When the cells were further cultured in the presence of β-glycerophosphate, ascorbic acid, and dexamethasone for 14 days, mineralized areas together with osteogenic differentiation evidenced by high alkaline phosphatase activity and osteocalcin contents were observed. The differentiation was confirmed at both protein and gene expression levels. The cells can also be cryopreserved and, after thawing, could show in vivo bone-forming capability. These results indicate that mesenchymal type cells localize in dental papilla and that the cells can be culture expanded/utilized for bone tissue engineering

  12. Hepatic regeneration and the epithelial to mesenchymal transition.

    Science.gov (United States)

    Xue, Zeng-Fu; Wu, Xiu-Min; Liu, Ming

    2013-03-07

    Liver injuries are repaired by fibrosis and regeneration. The core stage is the repair response and fibrosis formation as a scar. The cause of overly-responsive scar formation and diminished regeneration, especially in liver fibrosis and cirrhosis, is still unknown. The epithelial to mesenchymal transition (EMT), a previously discovered mechanism, plays an important role in liver fibrosis and tumor metastasis. Recently, EMT has been found to be associated with liver and bile duct cell fibrosis. Analyzing the established models and chronic disease processes, we propose that EMT liver cells may also lose their regenerative capability due to phenotype changes and that the remaining liver cells may quickly lose their regenerative capability in liver fibrosis or cirrhosis. Recognizing these phenotype changes or transition cells may play an important role in targeting therapy to reverse fibrosis not only by disrupting the transition that is necessary to produce the extracellular matrix but also by restoring the regenerative capacity of EMT-like cells.

  13. The Modulatory Effects of Mesenchymal Stem Cells on Osteoclastogenesis

    Science.gov (United States)

    Sharaf-Eldin, Wessam E.; Abu-Shahba, Nourhan; Mahmoud, Marwa; El-Badri, Nagwa

    2016-01-01

    The effect of mesenchymal stem cells (MSCs) on bone formation has been extensively demonstrated through several in vitro and in vivo studies. However, few studies addressed the effect of MSCs on osteoclastogenesis and bone resorption. Under physiological conditions, MSCs support osteoclastogenesis through producing the main osteoclastogenic cytokines, RANKL and M-CSF. However, during inflammation, MSCs suppress osteoclast formation and activity, partly via secretion of the key anti-osteoclastogenic factor, osteoprotegerin (OPG). In vitro, co-culture of MSCs with osteoclasts in the presence of high concentrations of osteoclast-inducing factors might reflect the in vivo inflammatory pathology and prompt MSCs to exert an osteoclastogenic suppressive effect. MSCs thus seem to have a dual effect, by stimulating or inhibiting osteoclastogenesis, depending on the inflammatory milieu. This effect of MSCs on osteoclast formation seems to mirror the effect of MSCs on other immune cells, and may be exploited for the therapeutic potential of MSCs in bone loss associated inflammatory diseases. PMID:26823668

  14. Osteoarthritis and Mesenchymal Stem Cell Therapy: An Overview

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Putri Purwanthi

    2017-08-01

    Full Text Available Osteoarthritis (OA is the most common form of arthritis that affects cartilage joints and leads to disability. OA becomes the major public health problem, as it is the most leading cause of disability and morbidity worldwide. Treatment choices for OA can be classified into several categories such as non-pharmacologic, pharmacologic, surgical therapy, and cell-based therapy. There is no curative treatment for OA, while conventional treatments that are commonly used focus on alleviating the pain as the main symptom of the disease. Mesenchymal stem cells (MSCs that can be found in several tissues of human body offer a new strategy for OA treatment owing to their ability to differentiate into chondrocytes. This article provides an overview about the basic concept of osteoarthritis as well as an insight about the MSCs therapy, including their basic characteristics, source, and transplantation strategies in the OA area.

  15. Mesenchymal Stem Cells and Their Clinical Applications in Osteoarthritis.

    Science.gov (United States)

    Chang, Yu-Hsun; Liu, Hwan-Wun; Wu, Kun-Chi; Ding, Dah-Ching

    2016-01-01

    Osteoarthritis is a chronic degenerative joint disorder characterized by articular cartilage destruction and osteophyte formation. Chondrocytes in the matrix have a relatively slow turnover rate, and the tissue itself lacks a blood supply to support repair and remodeling. Researchers have evaluated the effectiveness of stem cell therapy and tissue engineering for treating osteoarthritis. All sources of stem cells, including embryonic, induced pluripotent, fetal, and adult stem cells, have potential use in stem cell therapy, which provides a permanent biological solution. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, and umbilical cord show considerable promise for use in cartilage repair. MSCs can be sourced from any or all joint tissues and can modulate the immune response. Additionally, MSCs can directly differentiate into chondrocytes under appropriate signal transduction. They also have immunosuppressive and anti-inflammatory paracrine effects. This article reviews the current clinical applications of MSCs and future directions of research in osteoarthritis.

  16. Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

    Directory of Open Access Journals (Sweden)

    Maria Ausiliatrice Puglisi

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs, represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

  17. Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

    Science.gov (United States)

    Puglisi, Maria Ausiliatrice; Tesori, Valentina; Lattanzi, Wanda; Piscaglia, Anna Chiara; Gasbarrini, Giovanni Battista; D'Ugo, Domenico M.; Gasbarrini, Antonio

    2011-01-01

    Mesenchymal stem cells (MSCs), represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases. PMID:22228987

  18. Mesenchymal Stem Cells after Polytrauma: Actor and Target

    Directory of Open Access Journals (Sweden)

    Markus Huber-Lang

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent cells that are considered indispensable in regeneration processes after tissue trauma. MSCs are recruited to damaged areas via several chemoattractant pathways where they function as “actors” in the healing process by the secretion of manifold pro- and anti-inflammatory, antimicrobial, pro- and anticoagulatory, and trophic/angiogenic factors, but also by proliferation and differentiation into the required cells. On the other hand, MSCs represent “targets” during the pathophysiological conditions after severe trauma, when excessively generated inflammatory mediators, complement activation factors, and damage- and pathogen-associated molecular patterns challenge MSCs and alter their functionality. This in turn leads to complement opsonization, lysis, clearance by macrophages, and reduced migratory and regenerative abilities which culminate in impaired tissue repair. We summarize relevant cellular and signaling mechanisms and provide an up-to-date overview about promising future therapeutic MSC strategies in the context of severe tissue trauma.

  19. Circulating mesenchymal stem cells and their clinical implications

    Directory of Open Access Journals (Sweden)

    Liangliang Xu

    2014-01-01

    Full Text Available Circulating mesenchymal stem cells (MSCs is a new cell source for tissue regeneration and tissue engineering. The characteristics of circulating MSCs are similar to those of bone marrow-derived MSCs (BM-MSCs, but they exist at a very low level in healthy individuals. It has been demonstrated that MSCs are able to migrate to the sites of injury and that they have some distinct genetic profiles compared to BM-MSCs. The current review summaries the basic knowledge of circulating MSCs and their potential clinical applications, such as mobilizing the BM-MSCs into circulation for therapy. The application of MSCs to cure a broad spectrum of diseases is promising, such as spinal cord injury, cardiovascular repair, bone and cartilage repair. The current review also discusses the issues of using of allogeneic MSCs for clinical therapy.

  20. Mesenchymal stem cells homing to improve bone healing

    Directory of Open Access Journals (Sweden)

    Weiping Lin

    2017-04-01

    Full Text Available Cell therapy continues to attract growing interest as a promising approach to treat a variety of diseases. Mesenchymal stem cells (MSCs have been one of the most intensely studied candidates for cell therapy. Since the homing capacity of MSCs is an important determinant of effective MSC-based therapy, the enhancement of homing efficiency is essential for optimizing the therapeutic outcome. Furthermore, trafficking of endogenous MSCs to damaged tissues, also referred to as endogenic stem cell homing, and the subsequent participation of MSCs in tissue regeneration are considered to be a natural self-healing response. Therefore, strategies to stimulate and reinforce the mobilisation and homing of MSCs have become a key point in regenerative medicine. The current review focuses on advances in the mechanisms and factors governing trafficking of MSCs, and the relationship between MSC mobilisation and skeletal diseases, providing insights into strategies for their potential translational implications.

  1. Restoration of Corneal Transparency by Mesenchymal Stem Cells

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    Sharad K. Mittal

    2016-10-01

    Full Text Available Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF. Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy.

  2. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    Science.gov (United States)

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  3. Genetically engineered mesenchymal stem cells: applications in spine therapy.

    Science.gov (United States)

    Aslan, Hadi; Sheyn, Dima; Gazit, Dan

    2009-01-01

    Spine disorders and intervertebral disc degeneration are considered the main causes for the clinical condition commonly known as back pain. Spinal fusion by implanting autologous bone to produce bony bridging between the two vertebrae flanking the degenerated-intervertebral disc is currently the most efficient treatment for relieving the symptoms of back pain. However, donor-site morbidity, complications and the long healing time limit the success of this approach. Novel developments undertaken by regenerative medicine might bring more efficient and available treatments. Here we discuss the pros and cons of utilizing genetically engineered mesenchymal stem cells for inducing spinal fusion. The combination of the stem cells, gene and carrier are crucial elements for achieving optimal spinal fusion in both small and large animal models, which hopefully will lead to the development of clinical applications.

  4. Separation of Mesenchymal Stem Cells Through a Strategic Centrifugation Protocol.

    Science.gov (United States)

    Ferlin, Kimberly M; Kaplan, David S; Fisher, John P

    2016-04-01

    Despite great promise surrounding mesenchymal stem cells (MSCs), their implementation for tissue engineering strategies remains in the development phases. Many of the concerns regarding the clinical use of MSCs originate from population heterogeneity, during both isolation and differentiation. In this study, we utilize our previously developed centrifugation cell adhesion protocol for the separation of MSCs. Our findings reveal that MSCs can be isolated from whole bone marrow using a 200 g (700 pN) centrifugal force after 24 h of culture on polystyrene with cell surface marker expression equivalent to positive controls. During differentiation, a centrifugation protocol with identical force parameters could be applied 14 days into chondrogenic differentiation to isolate differentiated chondrocytes, which exhibited increased expression of chondrogenic markers compared to controls. In summary, the use of our developed centrifugation cell adhesion protocol has proven to be an effective means to separate MSC populations, decreasing the heterogeneity of subsequent cell therapy products.

  5. Epigenetic regulation of osteogenesis: human embryonic palatal mesenchymal cells.

    Science.gov (United States)

    Barkhordarian, Andre; Sison, Jay; Cayabyab, Riana; Mahanian, Nicole; Chiappelli, Francesco

    2011-01-06

    Mesenchymal stem cells (MSCs) provide an appropriate model to study epigenetic changes during osteogenesis and bone regeneration due to their differentiation potential. Since there are no unique markers for MSCs, methods of identification are limited. The complex morphology of human embryonic palatal mesenchyme stem cell (HEPM) requires analysis of fractal dimensions to provide an objective quantification of self-similarity, a statistical transformation of cellular shape and border complexity. We propose the hypothesis of a study to compare and contrast sequential steps of osteogenic differentiation in HEPMs both phenotypically using immunocytochemistry, and morphometrically using fractal analysis from undifferentiated passage 1 (P1) to passage 7 (P7) cells. The proof-of-concept is provided by results we present here that identify and compare the modulation of expression of certain epigenetic biomarkers (alkaline phosphatase, ALP; stromal interaction molecule-1, STRO-1; runt-related transcription factor-2, RUNX2), which are established markers of osteogenesis in bone marrow studies, of osteoblastic/skeletal morphogenesis, and of osteoblast maturation. We show that Osteoinductive medium (OIM) modulates the rate of differentiation of HEPM into Run-2+ cells, the most differentiated subpopulation, followed by ALP+ and STRO-1+ cells. Taken together, our phenotypical and morphometric data demonstrate the feasibility of using HEPM to assess osteogenic differentiation from an early undifferentiated to a differentiated stage. This research model may lay the foundation for future studies aimed at characterizing the epigenetic characteristics of osteoimmunological disorders and dysfunctions (e.g., osteoarthritis, temporomandibular joint disorders), so that proteomic profiling can aid the diagnosis and monitor the prognosis of these and other osteoimmunopathologies.

  6. Mesenchymal stem cells are highly resistant to sulfur mustard.

    Science.gov (United States)

    Schmidt, Annette; Scherer, Michael; Thiermann, Horst; Steinritz, Dirk

    2013-12-05

    The effect of sulfur mustard (SM) to the direct injured tissues of the skin, eyes and airways is well investigated. Little is known about the effect of SM to mesenchymal stem cells (MSC). However, this is an interesting aspect. Comparing the clinical picture of SM it is known today that MSC play an important role e.g. in chronic impaired wound healing. Therefore we wanted to get an understanding about how SM affects MSC and if these findings might become useful to get a better understanding of the effect of sulfur mustard gas with respect to skin wounds. We used mesenchymal stem cells, isolated from femoral heads from healthy donors and treated them with a wide range of SM to ascertain the dose-response-curve. With the determined inhibitory concentrations IC1 (1μM), IC5 (10μM), IC10 (20μM) and IC25 (40μM) we did further investigations. We analyzed the migratory ability and the differentiation capacity under influence of SM. Already very low concentrations of SM demonstrated a strong effect to the migratory activity whereas the differentiation capacity seemed not to be affected. Putting these findings together it seems to be likely that a link between MSC and the impaired wound healing after SM exposure might exist. Same as in patients with chronic impaired wound healing MSC had shown a reduced migratory activity. The fact that MSC are able to tolerate very high concentrations of SM and still do not lose their differentiation capacity may reveal new ways of treating wounds caused by sulfur mustard. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis.

    Science.gov (United States)

    Koh, Yong-Gon; Jo, Seung-Bae; Kwon, Oh-Ryong; Suh, Dong-Suk; Lee, Seung-Woo; Park, Sung-Ho; Choi, Yun-Jin

    2013-04-01

    The purpose of this study was to evaluate the clinical and imaging results of patients who received intra-articular injections of autologous mesenchymal stem cells for the treatment of knee osteoarthritis. The study group comprised 18 patients (6 men and 12 women), among whom the mean age was 54.6 years (range, 41 to 69 years). In each patient the adipose synovium was harvested from the inner side of the infrapatellar fat pad by skin incision extension at the arthroscopic lateral portal site after the patient underwent arthroscopic debridement. After stem cells were isolated, a mean of 1.18 × 10(6) stem cells (range, 0.3 × 10(6) to 2.7 × 10(6) stem cells) were prepared with approximately 3.0 mL of platelet-rich plasma (with a mean of 1.28 × 10(6) platelets per microliter) and injected into the selected knees of patients. Clinical outcome was evaluated with the Western Ontario and McMaster Universities Osteoarthritis Index, the Lysholm score, and the visual analog scale (VAS) for grading knee pain. We also compared magnetic resonance imaging (MRI) data collected both preoperatively and at the final follow-up. Western Ontario and McMaster Universities Osteoarthritis Index scores decreased significantly (P stem cells injected. The results of our study are encouraging and show that intra-articular injection of infrapatellar fat pad-derived mesenchymal stem cells is effective for reducing pain and improving knee function in patients being treated for knee osteoarthritis. Level IV, therapeutic case series. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  8. Endothelial-to-mesenchymal transition in pulmonary hypertension.

    Science.gov (United States)

    Ranchoux, Benoît; Antigny, Fabrice; Rucker-Martin, Catherine; Hautefort, Aurélie; Péchoux, Christine; Bogaard, Harm Jan; Dorfmüller, Peter; Remy, Séverine; Lecerf, Florence; Planté, Sylvie; Chat, Sophie; Fadel, Elie; Houssaini, Amal; Anegon, Ignacio; Adnot, Serge; Simonneau, Gerald; Humbert, Marc; Cohen-Kaminsky, Sylvia; Perros, Frédéric

    2015-03-17

    The vascular remodeling responsible for pulmonary arterial hypertension (PAH) involves predominantly the accumulation of α-smooth muscle actin-expressing mesenchymal-like cells in obstructive pulmonary vascular lesions. Endothelial-to-mesenchymal transition (EndoMT) may be a source of those α-smooth muscle actin-expressing cells. In situ evidence of EndoMT in human PAH was obtained by using confocal microscopy of multiple fluorescent stainings at the arterial level, and by using transmission electron microscopy and correlative light and electron microscopy at the ultrastructural level. Findings were confirmed by in vitro analyses of human PAH and control cultured pulmonary artery endothelial cells. In addition, the mRNA and protein signature of EndoMT was recognized at the arterial and lung level by quantitative real-time polymerase chain reaction and Western blot analyses. We confirmed our human observations in established animal models of pulmonary hypertension (monocrotaline and SuHx). After establishing the first genetically modified rat model linked to BMPR2 mutations (BMPR2(Δ140Ex1/+) rats), we demonstrated that EndoMT is linked to alterations in signaling of BMPR2, a gene that is mutated in 70% of cases of familial PAH and in 10% to 40% of cases of idiopathic PAH. We identified molecular actors of this pathological transition, including twist overexpression and vimentin phosphorylation. We demonstrated that rapamycin partially reversed the protein expression patterns of EndoMT, improved experimental PAH, and decreased the migration of human pulmonary artery endothelial cells, providing the proof of concept that EndoMT is druggable. EndoMT is linked to alterations in BPMR2 signaling and is involved in the occlusive vas cular remodeling of PAH, findings that may have therapeutic implications. © 2015 American Heart Association, Inc.

  9. Epithelial Mesenchymal Transition in Cancer Progression: Prev entive Phytochemicals.

    Science.gov (United States)

    Illam, Soorya P; Narayanankutty, Arunaksharan; Mathew, Shaji E; Valsalakumari, Remya; Jacob, Rosemol M; Raghavamenon, Achuthan C

    2017-01-01

    Epithelial-Mesenchymal Transition (EMT) is the conversion of epithelial cells into mesenchymal phenotype generally observed during embryogenesis and wound healing as well as in malignant transformation. Several signaling pathways and transcription factors associated with EMT have been explored. Dietary phytochemicals that are multi-targeted agents which interfere with these pathways, assume preventive potential against pathologic EMT. The present review aims to provide a detailed description of the nature and characteristics of EMT in physiological and pathophysiological conditions and the scope of phytochemicals in its prevention. Details regarding the initiation, progression as well as prevention of pathologic EMT and metastasis and recent patents on preventive phytochemicals were obtained from PubMed literatures and patent databases. The phenotypic changes during EMT are regulated by transcription factors like Snail, Slug, Twist and Zeb, which are activated through diverse signaling pathways of TGF-β, NF-kB, Wnt and Notch. s phytocompounds that are potent enough to interfere with these signaling pathways, which in turn prevent pathological implications of EMT. Present review also discusses 28 recent patents on those phytocompounds. EMT is a significant pharmacological target for developing preventive agents to combat pathological conditions like malignancy. Many of the phytochemicals cited in this review are being enrolled for different phases of clinical trials for their efficacy. In spite of the major limitations regarding bioavailability, sensitivity and tolerance of these compounds, their synthetic analogs, formulations and efficient drug delivery systems are also being attempted which will hopefully generate productive and promising results in near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Mesenchymal stem cell therapy for osteoarthritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Wyles CC

    2015-08-01

    Full Text Available Cody C Wyles,1 Matthew T Houdek,2 Atta Behfar,3 Rafael J Sierra,21Mayo Medical School, 2Department of Orthopedic Surgery, 3Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Osteoarthritis (OA is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.Keywords: mesenchymal stem cell, osteoarthritis, treatment, regenerative medicine, cell therapy

  11. Phosphaturic mesenchymal tumor of the tibia with oncogenic osteomalacia in a teenager.

    Science.gov (United States)

    Farmakis, Shannon G; Siegel, Marilyn J

    2015-08-01

    Phosphaturic mesenchymal tumor is an uncommon cause of a paraneoplastic syndrome that can be associated with osteogenic osteomalacia. This tumor most commonly occurs in middle-aged men and women. We report a rare case of a phosphaturic mesenchymal tumor in a 16-year-old girl with multiple fractures as a result of severe osteoporosis. CT and MRI showed a mass arising from the tibia.

  12. Oncostatin-M Differentially Regulates Mesenchymal and Proneural Signature Genes in Gliomas via STAT3 Signaling

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    Kumar Natesh

    2015-02-01

    Full Text Available Glioblastoma (GBM, the most malignant of the brain tumors is classified on the basis of molecular signature genes using TCGA data into four subtypes- classical, mesenchymal, proneural and neural. The mesenchymal phenotype is associated with greater aggressiveness and low survival in contrast to GBMs enriched with proneural genes. The proinflammatory cytokines secreted in the microenvironment of gliomas play a key role in tumor progression. The study focused on the role of Oncostatin-M (OSM, an IL-6 family cytokine in inducing mesenchymal properties in GBM. Analysis of TCGA and REMBRANDT data revealed that expression of OSMR but not IL-6R or LIFR is upregulated in GBM and has negative correlation with survival. Amongst the GBM subtypes, OSMR level was in the order of mesenchymal > classical > neural > proneural. TCGA data and RT-PCR analysis in primary cultures of low and high grade gliomas showed a positive correlation between OSMR and mesenchymal signature genes-YKL40/CHI3L1, fibronectin and vimentin and a negative correlation with proneural signature genes-DLL3, Olig2 and BCAN. OSM enhanced transcript and protein level of fibronectin and YKL-40 and reduced the expression of Olig2 and DLL3 in GBM cells. OSM-regulated mesenchymal phenotype was associated with enhanced MMP-9 activity, increased cell migration and invasion. Importantly, OSM induced mesenchymal markers and reduced proneural genes even in primary cultures of grade-III glioma cells. We conclude that OSM-mediated signaling contributes to aggressive nature associated with mesenchymal features via STAT3 signaling in glioma cells. The data suggest that OSMR can be explored as potential target for therapeutic intervention.

  13. Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation?

    OpenAIRE

    van Lent, Peter LEM; van den Berg, Wim B

    2013-01-01

    Although it is generally accepted that osteoarthritis is a degenerative condition of the cartilage, other tissues such as synovium in which immunological and inflammatory reactions occur contribute to the development of joint pathology. This sheds new light on the potential mechanism of action of mesenchymal stem cell therapy in osteoarthritis. Rather than tissue repair due to local transformation of injected mesenchymal stem cells to chondrocytes and filling defects in cartilage, such treatm...

  14. Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

    DEFF Research Database (Denmark)

    Haack-Sorensen, M.; Friis, T.; Bindslev, L.

    2008-01-01

    OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under...... compliant medium for MSC cultivation, expansion and differentiation. The expanded and differentiated MSCs can be used in autologous mesenchymal stromal cell therapy in patients with ischaemic heart disease Udgivelsesdato: 2008...

  15. Fate map of the dental mesenchyme: dynamic development of the dental papilla and follicle.

    Science.gov (United States)

    Rothová, Michaela; Peterková, Renata; Tucker, Abigail S

    2012-06-15

    At the bud stage of tooth development the neural crest derived mesenchyme condenses around the dental epithelium. As the tooth germ develops and proceeds to the cap stage, the epithelial cervical loops grow and appear to wrap around the condensed mesenchyme, enclosing the cells of the forming dental papilla. We have fate mapped the dental mesenchyme, using in vitro tissue culture combined with vital cell labelling and tissue grafting, and show that the dental mesenchyme is a much more dynamic population then previously suggested. At the bud stage the mesenchymal cells adjacent to the tip of the bud form both the dental papilla and dental follicle. At the early cap stage a small population of highly proliferative mesenchymal cells in close proximity to the inner dental epithelium and primary enamel knot provide the major contribution to the dental papilla. These cells are located between the cervical loops, within a region we have called the body of the enamel organ, and proliferate in concert with the epithelium to create the dental papilla. The condensed dental mesenchymal cells that are not located between the body of the enamel organ, and therefore are at a distance from the primary enamel knot, contribute to the dental follicle, and also the apical part of the papilla, where the roots will ultimately develop. Some cells in the presumptive dental papilla at the cap stage contribute to the follicle at the bell stage, indicating that the dental papilla and dental follicle are still not defined populations at this stage. These lineage-tracing experiments highlight the difficulty of targeting the papilla and presumptive odontoblasts at early stages of tooth development. We show that at the cap stage, cells destined to form the follicle are still competent to form dental papilla specific cell types, such as odontoblasts, and produce dentin, if placed in contact with the inner dental epithelium. Cell fate of the dental mesenchyme at this stage is therefore determined

  16. Larval mesenchyme cell specification in the primitive echinoid occurs independently of the double-negative gate.

    Science.gov (United States)

    Yamazaki, Atsuko; Kidachi, Yumi; Yamaguchi, Masaaki; Minokawa, Takuya

    2014-07-01

    Echinoids (sea urchins) are divided into two major groups - cidaroids (a 'primitive' group) and euechinoids (a 'derived' group). The cidaroids are a promising model species for understanding the ancestral developmental mechanisms in echinoids, but little is known about the molecular mechanisms of cidaroid development. In euechinoids, skeletogenic mesenchyme cell specification is regulated by the double-negative gate (DNG), in which hesC represses the transcription of the downstream mesenchyme specification genes (alx1, tbr and ets1), thereby defining the prospective mesenchyme region. To estimate the ancestral mechanism of larval mesenchyme cell specification in echinoids, the expression patterns and roles of mesenchyme specification genes in the cidaroid Prionocidaris baculosa were examined. The present study reveals that the expression pattern and function of hesC in P. baculosa were inconsistent with the DNG model, suggesting that the euechinoid-type DNG is not utilized during cidaroid mesenchyme specification. In contrast with hesC, the expression patterns and functions of alx1, tbr and ets1 were similar between P. baculosa and euechinoids. Based on these results, we propose that the roles of alx1, tbr and ets1 in mesenchyme specification were established in the common ancestor of echinoids, and that the DNG system was acquired in the euechinoid lineage after divergence from the cidaroid ancestor. The evolutionary timing of the establishment of the DNG suggests that the DNG was originally related to micromere and/or primary mesenchyme cell formation but not to skeletogenic cell differentiation. © 2014. Published by The Company of Biologists Ltd.

  17. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    OpenAIRE

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-l...

  18. Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy

    Science.gov (United States)

    2016-01-01

    The paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria. PMID:27651799

  19. Mesenchymal Stromal Cells Epithelial Transition Induced by Renal Tubular Cells-Derived Extracellular Vesicles.

    Directory of Open Access Journals (Sweden)

    Giulia Chiabotto

    Full Text Available Mesenchymal-epithelial interactions play an important role in renal tubular morphogenesis and in maintaining the structure of the kidney. The aim of this study was to investigate whether extracellular vesicles (EVs produced by human renal proximal tubular epithelial cells (RPTECs may induce mesenchymal-epithelial transition of bone marrow-derived mesenchymal stromal cells (MSCs. To test this hypothesis, we characterized the phenotype and the RNA content of EVs and we evaluated the in vitro uptake and activity of EVs on MSCs. MicroRNA (miRNA analysis suggested the possible implication of the miR-200 family carried by EVs in the epithelial commitment of MSCs. Bone marrow-derived MSCs were incubated with EVs, or RPTEC-derived total conditioned medium, or conditioned medium depleted of EVs. As a positive control, MSCs were co-cultured in a transwell system with RPTECs. Epithelial commitment of MSCs was assessed by real time PCR and by immunofluorescence analysis of cellular expression of specific mesenchymal and epithelial markers. After one week of incubation with EVs and total conditioned medium, we observed mesenchymal-epithelial transition in MSCs. Stimulation with conditioned medium depleted of EVs did not induce any change in mesenchymal and epithelial gene expression. Since EVs were found to contain the miR-200 family, we transfected MSCs using synthetic miR-200 mimics. After one week of transfection, mesenchymal-epithelial transition was induced in MSCs. In conclusion, miR-200 carrying EVs released from RPTECs induce the epithelial commitment of MSCs that may contribute to their regenerative potential. Based on experiments of MSC transfection with miR-200 mimics, we suggested that the miR-200 family may be involved in mesenchymal-epithelial transition of MSCs.

  20. We can Diagnose it if we Consider it. Diagnostic Pitfall for Placenta: Placental Mesenchymal Dysplasia

    Directory of Open Access Journals (Sweden)

    Havva Serap TORU

    2018-01-01

    Full Text Available Placental mesenchymal dysplasia is an increasingly recognizable abnormality. Early cases have been confused with partial hydatidiform mole. Placental mesenchymal dysplasia is probably under-diagnosed because of being an unfamiliar clinical entity and also mistaken for gestational trophoblastic disease due to the similar sonographic findings of two entities. In this report, we describe the clinical, gross, and histopathological findings of placental mesenchymal dysplasia in two cases. The 33-week-preterm baby of a 26-year-old woman with cardiovascular disease and 342 gram placenta and the 19-week fetus with trisomy 21 of a 40 year-old woman were terminated. Macroscopically thick-walled vessels and microscopically hydropic villous with peripherally localized thick-walled vessels without trophoblastic cell proliferation were observed in both cases. These two cases represent a rare placental anomaly that is benign but it is challenging to distinguish placental mesenchymal dysplasia from an incomplete mole. Placental mesenchymal dysplasia should be included in the differential diagnosis of sonographic findings that show a normal appearing fetus and a placenta with cystic lesions. Placental mesenchymal dysplasia is associated with pregnancy-related hypertension. In conclusion, the most important point is “you can diagnose it if you consider it”.

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

    Science.gov (United States)

    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.

  2. GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma.

    Science.gov (United States)

    Moreno, Marta; Pedrosa, Leire; Paré, Laia; Pineda, Estela; Bejarano, Leire; Martínez, Josefina; Balasubramaniyan, Veerakumar; Ezhilarasan, Ravesanker; Kallarackal, Naveen; Kim, Sung-Hak; Wang, Jia; Audia, Alessandra; Conroy, Siobhan; Marin, Mercedes; Ribalta, Teresa; Pujol, Teresa; Herreros, Antoni; Tortosa, Avelina; Mira, Helena; Alonso, Marta M; Gómez-Manzano, Candelaria; Graus, Francesc; Sulman, Erik P; Piao, Xianhua; Nakano, Ichiro; Prat, Aleix; Bhat, Krishna P; de la Iglesia, Núria

    2017-11-21

    A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM) and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and classical GBMs and is lost during their transition toward a mesenchymal subtype. GPR56 loss of function promotes mesenchymal differentiation and radioresistance of glioma initiating cells both in vitro and in vivo. Accordingly, a low GPR56-associated signature is prognostic of a poor outcome in GBM patients even within non-G-CIMP GBMs. Mechanistically, we reveal GPR56 as an inhibitor of the nuclear factor kappa B (NF-κB) signaling pathway, thereby providing the rationale by which this receptor prevents mesenchymal differentiation and radioresistance. A pan-cancer analysis suggests that GPR56 might be an inhibitor of the mesenchymal transition across multiple tumor types beyond GBM. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Carlos Augusto Galvão; Ginani, Fernanda [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil); Soares, Diego Moura [Universidade Federal de Pernambuco, Recife, PE (Brazil); Henriques, Águida Cristina Gomes; Freitas, Roseana de Almeida [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil)

    2014-07-01

    To evaluate the effect of low-level laser irradiation on the proliferation and possible nuclear morphological changes of mouse mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow and adipose tissue were submitted to two applications (T0 and T48 hours) of low-level laser irradiation (660nm; doses of 0.5 and 1.0J/cm{sup 2}). The trypan blue assay was used to evaluate cell viability, and growth curves were used to analyze proliferation at zero, 24, 48, and 72 hours. Nuclear alterations were evaluated by staining with DAPI (4'-6-diamidino-2-phenylindole) at 72 hours. Bone marrow-derived mesenchymal stem cells responded to laser therapy in a dose-dependent manner. Higher cell growth was observed when the cells were irradiated with a dose of 1.0J/cm{sup 2}, especially after 24 hours (p<0.01). Adipose-derived mesenchymal stem cells responded better to a dose of 1.0J/cm{sup 2}, but higher cell proliferation was observed after 48 hours (p<0.05) and 72 hours (p<0.01). Neither nuclear alterations nor a significant change in cell viability was detected in the studied groups. Low-level laser irradiation stimulated the proliferation of mouse mesenchymal stem cells without causing nuclear alterations. The biostimulation of mesenchymal stem cells using laser therapy might be an important tool for regenerative therapy and tissue engineering.

  4. Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

    International Nuclear Information System (INIS)

    Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

    2011-01-01

    Highlights: → Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. → The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. → Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

  5. Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells.

    Science.gov (United States)

    Zhang, Zhaocheng; Nör, Felipe; Oh, Min; Cucco, Carolina; Shi, Songtao; Nör, Jacques E

    2016-06-01

    Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/β-catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, β-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/β-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587. © 2016 AlphaMed Press.

  6. Evidences of early senescence in multiple myeloma bone marrow mesenchymal stromal cells.

    Directory of Open Access Journals (Sweden)

    Thibaud André

    Full Text Available BACKGROUND: In multiple myeloma, bone marrow mesenchymal stromal cells support myeloma cell growth. Previous studies have suggested that direct and indirect interactions between malignant cells and bone marrow mesenchymal stromal cells result in constitutive abnormalities in the bone marrow mesenchymal stromal cells. DESIGN AND METHODS: The aims of this study were to investigate the constitutive abnormalities in myeloma bone marrow mesenchymal stromal cells and to evaluate the impact of new treatments. RESULTS: We demonstrated that myeloma bone marrow mesenchymal stromal cells have an increased expression of senescence-associated β-galactosidase, increased cell size, reduced proliferation capacity and characteristic expression of senescence-associated secretory profile members. We also observed a reduction in osteoblastogenic capacity and immunomodulatory activity and an increase in hematopoietic support capacity. Finally, we determined that current treatments were able to partially reduce some abnormalities in secreted factors, proliferation and osteoblastogenesis. CONCLUSIONS: We showed that myeloma bone marrow mesenchymal stromal cells have an early senescent profile with profound alterations in their characteristics. This senescent state most likely participates in disease progression and relapse by altering the tumor microenvironment.

  7. BMP7 and EREG Contribute to the Inductive Potential of Dental Mesenchyme.

    Science.gov (United States)

    Gao, Bo; Zhou, Xin; Zhou, Xuedong; Pi, Caixia; Xu, Ruoshi; Wan, Mian; Yang, Jing; Zhou, Yue; Liu, Chengcheng; Sun, Jianxun; Zhang, Yan; Zheng, Liwei

    2015-05-08

    Odontogenesis is accomplished by reciprocal signaling between the epithelial and mesenchymal compartments. It is generally accepted that the inductive mesenchyme is capable of inducing the odontogenic commitment of both dental and non-dental epithelial cells. However, the duration of this signal in the developing dental mesenchyme and whether adult dental pulp tissue maintains its inductive capability remain unclear. This study investigated the contribution of growth factors to regulating the inductive potential of the dental mesenchyme. Human oral epithelial cells (OEs) were co-cultured with either human dental mesenchymal/papilla cells (FDPCs) or human dental pulp cells (ADPCs) under 2-dimensional or 3-dimensional conditions. Odontogenic-associated genes and proteins were detected by qPCR and immunofluorescence, respectively, and significant differences were observed between the two co-culture systems. The BMP7 and EREG expression levels in FDPCs were significantly higher than in ADPCs, as indicated by human growth factor PCR arrays and immunofluorescence analyses. OEs co-cultured with ADPCs supplemented with BMP7 and EREG expressed ameloblastic differentiation genes. Our study suggests that BMP7 and EREG expression in late bell-stage human dental papilla contributes to the inductive potential of dental mesenchyme. Furthermore, adult dental pulp cells supplemented with these two growth factors re-established the inductive potential of postnatal dental pulp tissue.

  8. Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells

    International Nuclear Information System (INIS)

    Barboza, Carlos Augusto Galvão; Ginani, Fernanda; Soares, Diego Moura; Henriques, Águida Cristina Gomes; Freitas, Roseana de Almeida

    2014-01-01

    To evaluate the effect of low-level laser irradiation on the proliferation and possible nuclear morphological changes of mouse mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow and adipose tissue were submitted to two applications (T0 and T48 hours) of low-level laser irradiation (660nm; doses of 0.5 and 1.0J/cm 2 ). The trypan blue assay was used to evaluate cell viability, and growth curves were used to analyze proliferation at zero, 24, 48, and 72 hours. Nuclear alterations were evaluated by staining with DAPI (4'-6-diamidino-2-phenylindole) at 72 hours. Bone marrow-derived mesenchymal stem cells responded to laser therapy in a dose-dependent manner. Higher cell growth was observed when the cells were irradiated with a dose of 1.0J/cm 2 , especially after 24 hours (p<0.01). Adipose-derived mesenchymal stem cells responded better to a dose of 1.0J/cm 2 , but higher cell proliferation was observed after 48 hours (p<0.05) and 72 hours (p<0.01). Neither nuclear alterations nor a significant change in cell viability was detected in the studied groups. Low-level laser irradiation stimulated the proliferation of mouse mesenchymal stem cells without causing nuclear alterations. The biostimulation of mesenchymal stem cells using laser therapy might be an important tool for regenerative therapy and tissue engineering

  9. Mechanisms of the epithelial-to-mesenchymal transition in sea urchin embryos

    Science.gov (United States)

    Katow, Hideki

    2015-01-01

    Sea urchin mesenchyme is composed of the large micromere-derived spiculogenetic primary mesenchyme cells (PMC), veg2-tier macromere-derived non-spiculogenetic mesenchyme cells, the small micromere-derived germ cells, and the macro- and mesomere-derived neuronal mesenchyme cells. They are formed through the epithelial-to-mesenchymal transition (EMT) and possess multipotency, except PMCs that solely differentiate larval spicules. The process of EMT is associated with modification of epithelial cell surface property that includes loss of affinity to the apical and basal extracellular matrices, inter-epithelial cell adherens junctions and epithelial cell surface-specific proteins. These cell surface structures and molecules are endocytosed during EMT and utilized as initiators of cytoplasmic signaling pathways that often initiate protein phosphorylation to activate the gene regulatory networks. Acquisition of cell motility after EMT in these mesenchyme cells is associated with the expression of proteins such as Lefty, Snail and Seawi. Structural simplicity and genomic database of this model will further promote detailed EMT research. PMID:26716069

  10. Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac1.

    Science.gov (United States)

    Nakaya, Yukiko; Kuroda, Shinya; Katagiri, Yuji T; Kaibuchi, Kozo; Takahashi, Yoshiko

    2004-09-01

    Mesenchymal-epithelial transitions (MET) are crucial for vertebrate organogenesis. The roles of Rho family GTPases in such processes during actual development remain largely unknown. By electroporating genes into chick presomitic mesenchymal cells, we demonstrate that Cdc42 and Rac1 play important and different roles in the MET that generates the vertebrate somites. Presomitic mesenchymal cells, which normally contribute to both the epithelial and mesenchymal populations of the somite, were hyperepithelialized when Cdc42 signaling was blocked. Conversely, cells taking up genes that elevate Cdc42 levels remained mesenchymal. Thus, Cdc42 activity levels appear critical for the binary decision that defines the epithelial and mesenchymal somitic compartments. Proper levels of Rac1 are necessary for somitic epithelialization, since cells with activated or inhibited Rac1 failed to undergo correct epithelialization. Furthermore, Rac1 appears to be required for Paraxis to act as an epithelialization-promoting transcription factor during somitogenesis.

  11. Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact.

    Science.gov (United States)

    Takigawa, Hidehiko; Kitadai, Yasuhiko; Shinagawa, Kei; Yuge, Ryo; Higashi, Yukihito; Tanaka, Shinji; Yasui, Wataru; Chayama, Kazuaki

    2017-05-01

    We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow-derived mesenchymal stem cells (MSCs) migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT)-related genes such as fibronectin (FN), SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury

    OpenAIRE

    Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal ...

  13. Advances in the Genetic Characterization of Cutaneous Mesenchymal Neoplasms: Implications for Tumor Classification and Novel Diagnostic Markers.

    Science.gov (United States)

    Compton, Leigh A; Doyle, Leona A

    2017-06-01

    Cutaneous mesenchymal neoplasms often pose significant diagnostic challenges; many such entities are rare or show clinical and histologic overlap with both other mesenchymal and non-mesenchymal lesions. Recent advances in the genetic classification of many cutaneous mesenchymal neoplasms have not only helped define unique pathologic entities and increase our understanding of their biology, but have also provided new diagnostic markers. This review details these recent discoveries, with a focus on their implications for tumor classification and diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord.

    Science.gov (United States)

    Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

    2014-09-15

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.

  15. Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yang, E-mail: Ly10160624@163.com; Han, Dong, E-mail: Donghan@bjmu.edu.cn; Wang, Lei, E-mail: wanglei_dentist@163.com; Feng, Hailan, E-mail: kqfenghl@bjmu.edu.cn

    2013-05-17

    Highlights: •Down-regulation of Wnt10a in dental mesenchymal cells impairs odontogenesis of reassociated tooth germs. •Dspp is down- and up-regulated after Wnt10a-knockdown and overexpression in dental mesenchymal cells. •Down-regulation of Wnt10a inhibits proliferation of dental mesenchymal cells. -- Abstract: The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10a impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation.

  16. Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells

    International Nuclear Information System (INIS)

    Liu, Yang; Han, Dong; Wang, Lei; Feng, Hailan

    2013-01-01

    Highlights: •Down-regulation of Wnt10a in dental mesenchymal cells impairs odontogenesis of reassociated tooth germs. •Dspp is down- and up-regulated after Wnt10a-knockdown and overexpression in dental mesenchymal cells. •Down-regulation of Wnt10a inhibits proliferation of dental mesenchymal cells. -- Abstract: The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10a impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation

  17. Impact of mesenchymal stem cell secreted PAI-1 on colon cancer cell migration and proliferation.

    Science.gov (United States)

    Hogan, Niamh M; Joyce, Myles R; Murphy, J Mary; Barry, Frank P; O'Brien, Timothy; Kerin, Michael J; Dwyer, Roisin M

    2013-06-14

    Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs+antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1 and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67-88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the significant functional impact of Mesenchymal Stem Cell-secreted PAI-1 on colon cancer cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

    Science.gov (United States)

    Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

    2014-01-01

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord. PMID:25374590

  19. AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs.

    Science.gov (United States)

    Collino, Federica; Bruno, Stefania; Incarnato, Danny; Dettori, Daniela; Neri, Francesco; Provero, Paolo; Pomatto, Margherita; Oliviero, Salvatore; Tetta, Ciro; Quesenberry, Peter J; Camussi, Giovanni

    2015-10-01

    Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell-promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI. Copyright © 2015 by the American Society of Nephrology.

  20. Células-tronco mesenquimais Mesenchymal stem cell

    Directory of Open Access Journals (Sweden)

    Betânia Souza Monteiro

    2010-02-01

    Full Text Available Dentre todas as células-tronco estudadas até o presente momento, as mesenquimais (MSC destacam-se por sua elevada plasticidade, podendo originar tecidos mesodermais e não mesodermais. Além disso, possuem características imunomoduladoras e imunossupressoras que ampliam as possibilidades de utilização terapêutica. As MSC secretam uma grande variedade de citocinas pró e anti-inflamatórias e fatores de crescimento e, por meio dessas moléculas bioativas, proporcionam a modulação da resposta inflamatória, o restabelecimento do suprimento vascular e a reparação adequada do tecido, contribuindo para a homeostasia tissular e imunológica sob condições fisiológicas. Também podem induzir as demais células presentes no nicho tecidual a secretarem outros fatores solúveis que estimulam a diferenciação dessas células indiferenciadas, favorecendo o processo de reparação. A terapia celular com MSC é uma alternativa terapêutica promissora, porém a compreensão da biologia dessas células ainda é uma ciência em formação. Este artigo tem por objetivo realizar uma breve revisão sobre as células mesenquimais indiferenciadas.Of all the stem cells studied so far, the mesenchymal stem cells (MSC stand out for their high plasticity and capacity of generating mesodermal and non-mesodermal tissues. In addition, immunomodulatory and immunosuppressive features that expand possibilities for therapeutic use are present in these cells. A variety of pro and anti-inflammatory cytokines and growth factors are secrete for MSC and provide a modulation of inflammatory response, re-establishment of vascular supply and adequate repair of the tissue, contributing to tissue homeostasis under physiologic conditions. Therefore, they can induce secretion of soluble factors that stimulate their differentiation by other cells present at the niche's tissue, promoting the repair process. Cell therapy using MSC is a promises therapeutic alternative, but

  1. Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β.

    Science.gov (United States)

    Mele, Valentina; Muraro, Manuele G; Calabrese, Diego; Pfaff, Dennis; Amatruda, Nunzia; Amicarella, Francesca; Kvinlaug, Brynn; Bocelli-Tyndall, Chiara; Martin, Ivan; Resink, Therese J; Heberer, Michael; Oertli, Daniel; Terracciano, Luigi; Spagnoli, Giulio C; Iezzi, Giandomenica

    2014-06-01

    Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor sites, where they can integrate into the tumor-associated stroma. However, molecular mechanisms and outcome of their interaction with cancer cells have not been fully clarified. In this study, we investigated the effects mediated by bone marrow-derived MSC on human colorectal cancer (CRC) cells in vitro and in vivo. We found that MSC triggered epithelial-to-mesenchymal transition (EMT) in tumor cells in vitro, as indicated by upregulation of EMT-related genes, downregulation of E-cadherin and acquisition of mesenchymal morphology. These effects required cell-to-cell contact and were mediated by surface-bound TGF-β newly expressed on MSC upon coculture with tumor cells. In vivo tumor masses formed by MSC-conditioned CRC cells were larger and characterized by higher vessel density, decreased E-cadherin expression and increased expression of mesenchymal markers. Furthermore, MSC-conditioned tumor cells displayed increased invasiveness in vitro and enhanced capacity to invade peripheral tissues in vivo. Thus, by promoting EMT-related phenomena, MSC appear to favor the acquisition of an aggressive phenotype by CRC cells. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  2. Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells.

    Science.gov (United States)

    Ricciardi, M; Zanotto, M; Malpeli, G; Bassi, G; Perbellini, O; Chilosi, M; Bifari, F; Krampera, M

    2015-03-17

    Epithelial-to-mesenchymal transition (EMT) has a central role in cancer progression and metastatic dissemination and may be induced by local inflammation. We asked whether the inflammation-induced acquisition of mesenchymal phenotype by neoplastic epithelial cells is associated with the onset of mesenchymal stromal cell-like immune-regulatory properties that may enhance tumour immune escape. Cell lines of lung adenocarcinoma (A549), breast cancer (MCF7) and hepatocellular carcinoma (HepG2) were co-cultured with T, B and NK cells before and after EMT induction by either the supernatant of mixed-lymphocyte reactions or inflammatory cytokines. EMT occurrence following inflammatory priming elicited multiple immune-regulatory effects in cancer cells resulting in NK and T-cell apoptosis, inhibition of lymphocyte proliferation and stimulation of regulatory T and B cells. Indoleamine 2,3-dioxygenase, but not Fas ligand pathway, was involved at least in part in these effects, as shown by the use of specific inhibitors. EMT induced by inflammatory stimuli confers to cancer cells some mesenchymal stromal cell-like immune-modulatory properties, which could be a cue for cancer progression and metastatic dissemination by favouring immune escape.

  3. Fuzheng Huayu Recipe Ameliorates Liver Fibrosis by Restoring Balance between Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition in Hepatic Stellate Cells

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    Qin Pan

    2015-01-01

    Full Text Available Activation of hepatic stellate cells (HSCs depending on epithelial-to-mesenchymal transition (EMT reflects the key event of liver fibrosis. Contrastively, mesenchymal-to-epithelial transition (MET of HSCs facilitates the fibrosis resolution. Here we investigated the effect of Fuzheng Huayu (FZHY recipe, a Chinese herbal decoction made of Radix Salviae Miltiorrhizae, Semen Persicae, Cordyceps sinensis, Pollen Pini, and Gynostemma pentaphyllum, on liver fibrosis concerning the balance of EMT and MET in HSCs. In contrast to the increased TGF-β1/BMP-7 ratio in activated HSCs, FZHY administration induced significant upregulation of BMP-7 and downregulation of TGF-β1 at both transcription and translation levels. Restoration of TGF-β1/BMP-7 ratio inhibited the expression of p38 MAPK and phosphorylated p38 MAPK, resulting in the reversal of epithelial-to-mesenchymal transition (EMT to mesenchymal-to-epithelial transition (MET as characterized by the abolishment of EMT markers (α-SMA and desmin and reoccurrence of MET marker (E-cadherin. In vivo treatment of FZHY recipe also demonstrated the statistical reduction of activated HSCs with EMT phenotype, which attenuated the carbon tetrachloride- (CCl4- induced liver fibrosis in a dose-dependent manner. These findings may highlight a novel antifibrotic role of FZHY recipe on the basis of rebalancing EMT and MET in HSCs.

  4. Collagen gel contraction serves to rapidly distinguish epithelial- and mesenchymal-derived cells irrespective of alpha-smooth muscle actin expression

    DEFF Research Database (Denmark)

    Nielsen, Helga Lind; Gudjonsson, Thorarinn; Villadsen, René

    2004-01-01

    Mesenchymal-like cells in the stroma of breast cancer may arise as a consequence of plasticity within the epithelial compartment, also referred to as epithelial-mesenchymal transition, or by recruitment of genuine mesenchymal cells from the peritumoral stroma. Cells of both the epithelial...... under these conditions did not augment contractility. It is concluded that epithelial-derived mesenchymal-like cells are functionally defective within a connective tissue environment irrespective of an apparent contractile phenotype....

  5. Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine.

    Science.gov (United States)

    Nowakowski, Adam; Walczak, Piotr; Janowski, Miroslaw; Lukomska, Barbara

    2015-10-01

    Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented.

  6. Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells

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    Amitabh C. Pandey

    2017-01-01

    Full Text Available Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.

  7. Immunolocalization of endocan during the endothelial-mesenchymal transition process

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    L. M. Carrillo

    2011-06-01

    Full Text Available Endocan is a dermatan sulfate proteoglycan (DSPG that has been observed in the cytoplasm of endothelial cells of small and large vessels in lung, kidney, liver, colon, ovary and brain tumors. This DSPG has been implicated in the regulation of cellular activities such as adhesion, migration, and proliferation. Given the important roles played by endocan in such processes, we sought to determine whether this DSPG is present in the chicken embryo aortic wall in embryonic days 12 and 14 when intimal thickening and endothelial transformation are notorious. Immunolabeling of serial paraffin cross-sections revealed endocan immunoreactivity at the endothelium and some mesenchymal cells constituting the intimal thickening but not in the cells arranged in lamellar layers. We also investigated whether endocan was present in monolayers of primary embryonic aortic endothelial cells attached to fibronectin and stimulated with epidermal growth factor. Endocan immunoreactivity was detected at the plasma membrane in arrays typical of focal complexes in the leading edge of the cells that were separating, detaching, and migrating toward cell-free areas. This study demonstrates for the first time the presence of endocan during the aortic wall remodeling, and provides evidence that suggests a possible contribution of this DSPG in the EndoMT process.

  8. Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

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    Dixin Cui

    2017-01-01

    Full Text Available Temporomandibular joint osteoarthritis (TMJ OA is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs, derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering.

  9. Concave microwell plate facilitates chondrogenesis from mesenchymal stem cells.

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    Ko, Ji-Yun; Im, Gun-Il

    2016-11-01

    To compare in vitro chondrogenesis from bone marrow-derived mesenchymal stem cells using concave microwell plates with those obtained using culture tubes. Pellets cultured in concave microwell plates had a significantly higher level of GAG per DNA content and greater proteoglycan content than those cultured in tubes at day 7 and 14. Three chondrogenic markers, SOX-9, COL2A1 and aggrecan, showed significantly higher expression in pellets cultured in concave microwell plates than those cultured in tubes at day 7 and 14. At day 21, there was not a significant difference in the expression of these markers. COL10A1, the typical hypertrophy marker, was significantly lower in concave microwell plates during the whole culture period. Runx-2, a marker of hypertrophy and osteogenesis, was significantly lower at day 7 in pellets cultured in concave microwell plates than those cultured in tubes. Concave microwell plates provide a convenient and effective tool for the study of in vitro chondrogenesis and may replace the use of propylene culture tube.

  10. Mesenchymal Stem Cells Mitigate Cirrhosis through BMP7

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    Bing Li

    2015-01-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs has therapeutic effects on various diseases, while its effect on developing cirrhosis as well as the underlying mechanism remained largely unknown. Methods: Twenty C57BL/6 mice were randomly separated into 2 groups of ten each. One group received transplantation of MSCs, while the other group received saline as control. The mice then received intraperitoneal injection of carbon tetrachloride (CCl4 twice per week for 8 weeks to develop cirrhosis. After another 4 weeks, the levels of cirrhosis in these mice were evaluated by liver fibrosis area, portal pressure, sodium balance and excretion. Transcripts of transforming growth factor β 1 (TGFβ1 and bone morphogenic protein 7 (BMP7 in the mouse livers were quantified by RT-qPCR. BMP7-depleted MSCs were prepared and applied in this model, and compared to MSCs. Results: Liver fibrosis, portal hypertension and sodium retention that were developed by CCl4, were all significantly alleviated by MSCs transplantation, which decreased TGFβ1 levels and increased BMP7 levels in the injured liver. MSCs were found to express extremely high levels of BMP7. Knockdown of BMP7 in MSCs completely abolished the protective effect of MSCs against CCl4-induced cirrhosis. Conclusions: MSCs mitigate cirrhosis through their production of BMP7 against the fibrogenic effect of TGFβ1 in the injured liver.

  11. Guidance of mesenchymal stem cells on fibronectin structured hydrogel films.

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    Annika Kasten

    Full Text Available Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN that was homogeneously immmobilized to NCO-sP(EO-stat-PO, which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.

  12. Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases

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    Andrea Farini

    2014-01-01

    Full Text Available Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials.

  13. Mesenchymal stromal cells ameliorate acute allergic rhinitis in rats.

    Science.gov (United States)

    Li, Chunlei; Fu, Yanxia; Wang, Yinyin; Kong, Yanhua; Li, Mengdi; Ma, Danhui; Zhai, Wanli; Wang, Hao; Lin, Yuting; Liu, Sihan; Ren, Fangli; Li, Jun; Wang, Yi

    2017-10-01

    Mesenchymal stromal cells (MSCs) have been extensively investigated as a potential antiinflammatory treatment in many inflammatory-related diseases; however, it remains unclear whether MSCs could be used to treat acute allergic rhinitis. A rat model of allergic rhinitis was treated with MSCs. The effect of MSCs on the inflammation of allergic rhinitis was evaluated by sneezing, nose rubbing, the pathology of the nasal mucosa, and the expression of interleukin 4, tumour necrosis factor alpha, and immunoglobulin E in the serum of rats. Also, the population of MSCs isolated from umbilical cords of humans was evaluated to determine if they could inhibit the symptoms and inflammation of acute allergic rhinitis in a rat model. We observed that this population of cells inhibited sneezing, nose rubbing, and changes in the pathology of the nasal mucosa. Intriguingly, we observed that MSCs reduced the expression of interleukin 4, tumour necrosis factor alpha, and immunoglobulin E in the serum. Furthermore, MSCs reduced the expression of histamine and the recruitment of macrophages in the nasal mucosa of allergic rhinitis rats. We reasoned that the effect of MSCs on allergic rhinitis might be through its regulation of the secretion of related cytokines from macrophages during the process of acute allergic rhinitis. This work suggested that MSCs from the umbilical cords of humans could be used as a positive clinical therapy for the human disease. Copyright © 2017 The Authors Cell Biochemistry & Function Published by John Wiley & Sons Ltd.

  14. Ion Channels in Hematopoietic and Mesenchymal Stem Cells

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    Serena Pillozzi

    2012-01-01

    Full Text Available Hematopoietic stem cells (HSCs reside in bone marrow niches and give rise to hematopoietic precursor cells (HPCs. These have more restricted lineage potential and eventually differentiate into specific blood cell types. Bone marrow also contains mesenchymal stromal cells (MSCs, which present multilineage differentiation potential toward mesodermal cell types. In bone marrow niches, stem cell interaction with the extracellular matrix is mediated by integrin receptors. Ion channels regulate cell proliferation and differentiation by controlling intracellular Ca2+, cell volume, release of growth factors, and so forth. Although little evidence is available about the ion channel roles in true HSCs, increasing information is available about HPCs and MSCs, which present a complex pattern of K+ channel expression. K+ channels cooperate with Ca2+ and Cl− channels in regulating calcium entry and cell volume during mitosis. Other K+ channels modulate the integrin-dependent interaction between leukemic progenitor cells and the niche stroma. These channels can also regulate leukemia cell interaction with MSCs, which also involves integrin receptors and affects the MSC-mediated protection from chemotherapy. Ligand-gated channels are also implicated in these processes. Nicotinic acetylcholine receptors regulate cell proliferation and migration in HSCs and MSCs and may be implicated in the harmful effects of smoking.

  15. Growth Hormone and the Epithelial-to-Mesenchymal Transition.

    Science.gov (United States)

    Brittain, Alison L; Basu, Reetobrata; Qian, Yanrong; Kopchick, John J

    2017-10-01

    Previous studies have implicated growth hormone (GH) in the progression of several cancers, including breast, colorectal, and pancreatic. A mechanism by which GH may play this role in cancer is through the induction of the epithelial-to-mesenchymal transition (EMT). During the EMT process, epithelial cells lose their defining phenotypes, causing loss of cellular adhesion and increased cell migration. This review aims to carefully summarize the previous two decades of research that points to GH as an initiator of EMT, in both cancerous and noncancerous tissues. Sources were collected using PubMed and Google Scholar search engines by using specific GH- and/or EMT-related terms. Identified manuscripts were selected for further analysis based on presentation of GH-induced molecular markers of the EMT process in vivo or in vitro. Cellular mechanisms involved in GH-induced EMT are the focus of this review, both in cancerous and noncancerous epithelial cells. Our findings suggest that a myriad of molecular mechanisms are induced by GH that cause EMT and may point to potential therapeutic use of GH antagonists or any downregulator of GH action in EMT-related disease. Copyright © 2017 Endocrine Society

  16. Mesenchymal Stem Cells for Treating Articular Cartilage Defects and Osteoarthritis.

    Science.gov (United States)

    Wang, Yu; Yuan, Mei; Guo, Quan-yi; Lu, Shi-bi; Peng, Jiang

    2015-01-01

    Articular cartilage damage and osteoarthritis are the most common joint diseases. Joints are prone to damage caused by sports injuries or aging, and such damage regularly progresses to more serious joint disorders, including osteoarthritis, which is a degenerative disease characterized by the thinning and eventual wearing out of articular cartilage, ultimately leading to joint destruction. Osteoarthritis affects millions of people worldwide. Current approaches to repair of articular cartilage damage include mosaicplasty, microfracture, and injection of autologous chondrocytes. These treatments relieve pain and improve joint function, but the long-term results are unsatisfactory. The long-term success of cartilage repair depends on development of regenerative methodologies that restore articular cartilage to a near-native state. Two promising approaches are (i) implantation of engineered constructs of mesenchymal stem cell (MSC)-seeded scaffolds, and (ii) delivery of an appropriate population of MSCs by direct intra-articular injection. MSCs may be used as trophic producers of bioactive factors initiating regenerative activities in a defective joint. Current challenges in MSC therapy are the need to overcome current limitations in cartilage cell purity and to in vitro engineer tissue structures exhibiting the required biomechanical properties. This review outlines the current status of MSCs used in cartilage tissue engineering and in cell therapy seeking to repair articular cartilage defects and related problems. MSC-based technologies show promise when used to repair cartilage defects in joints.

  17. Mesenchymal stem cells for cartilage regeneration in osteoarthritis.

    Science.gov (United States)

    Kristjánsson, Baldur; Honsawek, Sittisak

    2017-09-18

    Osteoarthritis (OA) is a slowly progressive disease where cartilage of the synovial joint degenerates. It is most common in the elderly where patients experience pain and reduce physical activity. In combination with lack of conventional treatment, patients are often left with no other choices than arthroplasty. Over the last years, multipotent stromal cells have been used in efforts to treat OA. Mesenchymal stem/progenitor cells (MSCs) are stromal cells that can differentiate into bone, fat, and cartilage cells. They reside within bone marrow and fat. MSCs can also be found in synovial joints where they affect the progression of OA. They can be isolated and proliferated in an incubator before being applied in clinical trials. When it comes to treatment, emphasis has hitherto been on autologous MSCs, but allogenic cells from healthy donors are emerging as another source of the cells. The first adaptations of MSCs revolved in the use of cell-rich matrix, delivered as invasive surgical procedure, which resulted in production of hyaline cartilage and fibrocartilage. However, the demand for less invasive delivery of cells has prompted the use of direct intra-articular injections, wherein a large amount of suspended cells are implanted in the cartilage defect.

  18. Therapeutic application of mesenchymal stem cells in osteoarthritis.

    Science.gov (United States)

    Ruiz, Maxime; Cosenza, Stella; Maumus, Marie; Jorgensen, Christian; Noël, Danièle

    2016-01-01

    Osteoarthritis (OA) is a degenerative disease characterized by cartilage degradation and subchondral bone alterations. This disease represents a global public health problem whose prevalence is rapidly growing with the increasing aging of the population. With the discovery of mesenchymal stem cells (MSC) as possible therapeutic agents, their potential for repairing cartilage damage in OA is under investigation. Characterization of MSCs and their functional properties are mentioned with an insight into their trophic function and secretory profile. We present a special focus on the types of extracellular vesicles (EVs) that are produced by MSCs and their role in the paracrine activity of MSCs. We then discuss the therapeutic approaches that have been evaluated in pre-clinical models of OA and the results coming out from the clinical trials in patients with OA. MSC-based therapy seems a promising approach for the treatment of patients with OA. Further research is still needed to demonstrate their efficacy in clinical trials using controlled, prospective studies. However, the emergence of MSC-derived EVs as possible therapeutic agents could be an alternative to cell-based therapy.

  19. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

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    Sean D. Owens

    2016-01-01

    Full Text Available Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM or adipose tissue derived MSCs (ad-MSCs were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89% were positive for anti-bovine serum albumin (BSA antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  20. Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells

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    Aanei, Carmen Mariana, E-mail: caanei@yahoo.com [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Eloae, Florin Zugun [Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Flandrin-Gresta, Pascale [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Tavernier, Emmanuelle [Service Hematologie Clinique, Institut de Cancerologie de la Loire, 42270, Saint-Priest-en-Jarez (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Carasevici, Eugen [Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania); Guyotat, Denis [Service Hematologie Clinique, Institut de Cancerologie de la Loire, 42270, Saint-Priest-en-Jarez (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France); Campos, Lydia [Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France); CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne (France)

    2011-11-01

    Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their cellular microenvironment is essential to maintain 'stemness'. In cancer biology, focal adhesion (FA) proteins are involved in survival signal transduction in a wide variety of human tumours. To define the role of FA proteins in the haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and p130CAS, and analysed for reactivity, intensity and cellular localisation. Immunofluorescence microscopy allowed us to identify qualitative and quantitative differences, and subcellular localisation analysis revealed that in pathological MSCs, paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and enhanced nuclear co-localisation of these proteins correlated with a consistent proliferative advantage in MSCs from patients with refractory anaemia with excess blasts (RAEB) and negatively impacted clonogenicity of HPCs. These results suggest that signalling via FA proteins could be implicated in HPC-MSC interactions. Further, because FAK is an HSP90{alpha}/{beta} client protein, these results suggest the utility of HSP90{alpha}/{beta} inhibition as a target for adjuvant therapy for myelodysplasia.