Follicle development in cryopreserved bitch ovarian tissue grafted to immunodeficient mouse

The present study evaluated: (1) in vivo follicular development in canine ovarian tissue after slow freezing and xenotransplantation; and (2) the use of erythropoietin (EPO) as an angiogenic factor to optimise the transplantation procedure. Frozen–thawed ovarian tissue from five bitches was grafted into severe combined immunodeficient (SCID) mice (n = 47) treated with or without EPO (500 IU kg–1, once daily for 3 days) (Groups A and B, respectively) and analysed after 0, 1, 8 or 16 weeks. Follicle grade, follicle density, follicle morphology and stromal cells density were assessed by histological analysis, whereas vascularisation of the graft was quantified by immunohistochemistry with anti-α-smooth muscle actin antibody. Despite a massive loss of follicles after grafting, secondary follicle density was higher at 8 and 16 weeks than at 1 week regardless of EPO treatment. EPO significantly improved early follicle morphology and stromal cell density after 8 weeks and blood vessel density at 16 weeks after transplantation (P < 0.05). Intact secondary follicles with more than three granulosa cells layers were observed 16 weeks after transplantation. The results suggest that canine ovarian tissue can be successfully preserved by our slow-freezing protocol because the tissue showed follicular growth after xenotransplantation. EPO treatment did not lessen the massive loss of follicles after transplantation.

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A Step Forward Toward the Understanding of the Long-Term Pathogenesis of Double Capsule Formation in Macrotextured Implants: A Prospective Histological Analysis

Aesthetic Surgery Journal ◽

10.1093/asj/sjy293 ◽

2018 ◽

Vol 39 (11) ◽

pp. 1191-1199 ◽

Cited By ~ 3

Author(s):

Caroline A Glicksman ◽

Michel A Danino ◽

Johnny I Efanov ◽

Arij El Khatib ◽

Monica Nelea

Keyword(s):

Smooth Muscle ◽

Histological Analysis ◽

Incidental Finding ◽

Smooth Muscle Actin ◽

Muscle Actin ◽

Alpha Smooth Muscle Actin ◽

Level Of Evidence ◽

Staining Techniques ◽

Hematoxylin And Eosin ◽

Mechanical Shearing

Abstract Background Although increasingly reported in the literature, most plastic surgeons cannot define the etiology of double capsules. Often an incidental finding at implant exchange, double capsules are frequently associated with macrotextured devices. Several mechanisms have been proposed, including at the forefront that shearing causes a delamination of the periprosthetic capsule into a double capsule. Objectives This study was designed to confirm the hypothesis that mechanical forces are involved in formation of double capsules by histological analysis. Methods A prospective analysis of consecutive implants with double capsules removed over 2 years was performed. Data collected at the time of surgery included Baker classification, reason for explant, implant manufacturer and style, and any presence of a seroma associated with the capsule. Specimens were sent for analysis by histology utilizing hematoxylin and eosin and alpha-smooth muscle actin staining techniques. Results Eight double capsules were collected for specimen analysis. All capsules demonstrated evidence of granulation tissue, alpha-smooth muscle actin positive myofibroblasts, and folds with embedded texture. Fibrosis surrounded weak areas with presence of layering and splitting, creating a potential space that is prone to separation. Tears and folds from granulomatous reaction are also present within the outer layer of the double capsule, which can only be explained by a mechanical shearing force as a pathogenic mechanism. Conclusions Understanding the pathogenesis of double capsules may allow plastic surgeons to refine their indications for macrotextured implants while providing guidance to patients on avoidance of activities that produce shear-forces. The findings support the hypothesis that shearing forces delaminate the capsule into 2 separate distinct capsules. Level of Evidence: 5

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A stable explant culture of HER2/neu invasive carcinoma supported by alpha-Smooth Muscle Actin expressing stromal cells to evaluate therapeutic agents

BMC Cancer ◽

10.1186/1471-2407-8-119 ◽

2008 ◽

Vol 8 (1) ◽

Cited By ~ 2

Author(s):

Marie P Piechocki

Keyword(s):

Smooth Muscle ◽

Stromal Cells ◽

Invasive Carcinoma ◽

Smooth Muscle Actin ◽

Therapeutic Agents ◽

Explant Culture ◽

Muscle Actin ◽

Alpha Smooth Muscle Actin

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β-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse

The Journal of Cell Biology ◽

10.1083/jcb.200403050 ◽

2004 ◽

Vol 166 (3) ◽

pp. 359-367 ◽

Cited By ~ 269

Author(s):

Stefan Liebner ◽

Anna Cattelino ◽

Radiosa Gallini ◽

Noemi Rudini ◽

Monica Iurlaro ◽

...

Keyword(s):

Wnt Signaling ◽

Heart Development ◽

Transcriptional Activity ◽

Ex Vivo ◽

Smooth Muscle Actin ◽

Muscle Actin ◽

Endocardial Cushions ◽

Smad Phosphorylation ◽

Mesenchymal Transformation

During heart development endocardial cells within the atrio-ventricular (AV) region undergo TGFβ-dependent epithelial-mesenchymal transformation (EMT) and invade the underlying cardiac jelly. This process gives rise to the endocardial cushions from which AV valves and part of the septum originate. In this paper we show that in mouse embryos and in AV explants TGFβ induction of endocardial EMT is strongly inhibited in mice deficient for endothelial β-catenin, leading to a lack of heart cushion formation. Using a Wnt-signaling reporter mouse strain, we demonstrated in vivo and ex vivo that EMT in heart cushion is accompanied by activation of β-catenin/TCF/Lef transcriptional activity. In cultured endothelial cells, TGFβ2 induces α-smooth muscle actin (αSMA) expression. This process was strongly reduced in β-catenin null cells, although TGFβ2 induced smad phosphorylation was unchanged. These data demonstrate an involvement of β-catenin/TCF/Lef transcriptional activity in heart cushion formation, and suggest an interaction between TGFβ and Wnt-signaling pathways in the induction of endothelial-mesenchymal transformation.

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Epithelial Cells and Their Neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00075.2005 ◽

2005 ◽

Vol 289 (1) ◽

pp. G2-G7 ◽

Cited By ~ 129

Author(s):

D. W. Powell ◽

P. A. Adegboyega ◽

J. F. Di Mari ◽

R. C. Mifflin

Keyword(s):

Lamina Propria ◽

Information Flow ◽

Stromal Cells ◽

Smooth Muscle Actin ◽

Distant Metastases ◽

Muscle Actin ◽

Mural Cells ◽

Intestinal Neoplasms ◽

Extracellular Matrix Molecules

Intestinal myofibroblasts are α-smooth muscle actin-positive stromal cells that exist as a syncytium with fibroblasts and mural cells in the lamina propria of the gut. Through expression and secretion of cytokines, chemokines, growth factors, prostaglandins, and basal lamina/extracellular matrix molecules, as well as expression of adhesion molecules and receptors for many of the same soluble factors and matrix, myofibroblasts mediate information flow between the epithelium and the mesenchymal elements of the lamina propria. With the use of these factors and receptors, they play a fundamental role in intestinal organogenesis and in the repair of wounding or disease. Intestinal neoplasms enlist and conscript myofibroblast factors and matrix molecules to promote neoplastic growth, carcinoma invasion, and distant metastases.

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Stromal Incorporation of VEGFR-1+, CD68+ and α-SMA+ Hemangiogenic Cells Correlates with Histologic Subtype in Non-Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v106.11.1930.1930 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1930-1930 ◽

Cited By ~ 1

Author(s):

Jia Ruan ◽

Elizabeth Hyjek ◽

Andrea T. Hooper ◽

Loic Vincent ◽

Pouneh Kermani ◽

...

Keyword(s):

Smooth Muscle ◽

Stromal Cells ◽

Smooth Muscle Actin ◽

Hematopoietic Cells ◽

Hodgkin's Lymphoma ◽

Muscle Actin ◽

Alpha Smooth Muscle Actin ◽

Stromal Compartment ◽

Non Hodgkin's Lymphoma ◽

Benign Hyperplasia

Abstract BACKGROUND: Tumor stromal environment has been increasingly recognized to contribute to tumorigenesis. Vascular endothelial growth factor receptor-1+ (VEGFR-1+) hematopoietic cells and alpha-smooth muscle actin+ (α-SMA+) stromal cells both contribute to tumor neo-angiogenesis. However, their roles in promoting neo-angiogenesis specifically in human lymphomas remain unknown. METHODS: We examined the spatial localization of vascular and stromal cells expressing CD34 (vasculature), α-SMA (stromal cells), VEGFR-1 (hematopoietic cells and neo-vessels) and CD68 (myelomonocytic hematopoietic cells) by immunohistochemistry in 42 cases of non-Hodgkin’s lymphoma (NHL) specimens, which include diffuse large B-cell lymphoma (DLBCL, n=28), Burkitt lymphoma (BL, n=2), follicular lymphoma (FL, n=7), and chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL, n=5). RESULTS: There was a significant increase in CD68+ hematopoietic cells and a profound increase in the tissue hemangiogenic index, as defined by the degree of infiltration of both VEGFR-1+ neo-vessels and CD68+ cells, in aggressive lymphomas including DLBCL as compared to the indolent subtypes. Specifically, CD68 cell counts (mean±S.E. in 200X high power field (HPF)) for aggressive vs. indolent vs. benign hyperplasia were: 235.48±16.91 (n=30) vs. 35.98±4.48 (n=12) vs. 79.06±12.41 (n=5), p<0.0001 by ANOVA test; hemangiogenic index for DLBCL vs. CLL vs. FL: 18.14±1.27% (n=5) vs. 3.39±0.97% (n=4) vs. 6.08±1.26% (n=5), p< 0.0001. Transformed DLBCL (from indolent subtypes) had a similar increase in CD68+ cells compared to de novo DLBCL (193.97±58.10 (n=5) vs. 241.77±18.15 (n=23), p=0.81). In DLBCL, CD68+ cells were localized to the peri-endothelial region of the VEGFR-1+ neo-vessels and stromal compartment. Remarkably, although the expression of alpha-smooth muscle actin (α-SMA) was barely detectable in the aggressive subtypes, there was a profound diffuse increase of α-SMA throughout the stromal compartment of CLL/SLL. Surprisingly, there was no correlation between the CD34+ microvessel density (MVD) and the lymphoma subtypes (aggressive vs. indolent vs. benign hyperplasia: 39.29±3.42 vs. 41.88±5.38 vs. 47.92±5.84, p=0.61). CONCLUSIONS: These data introduce the novel concept that the extent of vessel density has no correlation with the histologic grade of lymphomas. However, the stromal hemangiogenic index, as quantified by the incorporation of CD68+, VEGFR-1+, and α-SMA+ cells, correlates with NHL subtypes. Increased incorporation of pro-angiogenic CD68+ cells and diminished localization of α-SMA+ cells to the peri-vascular zone may contribute to enhanced neo-angiogenesis and tumor growth in DLBCL; while decrease in the CD68+ cells and increase in the α-SMA+ cells may promote neo-vessel stability in CLL/SLL. Thus stromal hemangiogenic components in lymphoma could potentially be targeted for therapeutic intervention.

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Combination of 13-Cis Retinoic Acid and Lovastatin: Marked Antitumor Potential In Vivo in a Pheochromocytoma Allograft Model in Female Athymic Nude Mice

Endocrinology ◽

10.1210/en.2014-1027 ◽

2014 ◽

Vol 155 (7) ◽

pp. 2377-2390 ◽

Cited By ~ 8

Author(s):

Svenja Nölting ◽

Alessio Giubellino ◽

Yasin Tayem ◽

Karen Young ◽

Michael Lauseker ◽

...

Keyword(s):

Smooth Muscle ◽

Retinoic Acid ◽

Smooth Muscle Actin ◽

Treated Group ◽

Muscle Actin ◽

Tumor Mass ◽

Viable Tumor ◽

Over Time

Currently, there are no reliably effective therapeutic options for metastatic pheochromocytoma (PCC) and paraganglioma. Moreover, there are no therapies that may prevent the onset or progression of tumors in patients with succinate dehydrogenase type B mutations, which are associated with very aggressive tumors. Therefore, we tested the approved and well-tolerated drugs lovastatin and 13-cis-retinoic acid (13cRA) in vitro in an aggressive PCC mouse cell line, mouse tumor tissue-derived (MTT) cells, and in vivo in a PCC allograft nude mouse model, in therapeutically relevant doses. Treatment was started 24 hours before sc tumor cell injection and continued for 30 more days. Tumor sizes were measured from outside by caliper and sizes of viable tumor mass by bioluminescence imaging. Lovastatin showed antiproliferative effects in vitro and led to significantly smaller tumor sizes in vivo compared with vehicle treatment. 13cRA promoted tumor cell growth in vitro and led to significantly larger viable tumor mass and significantly faster increase of viable tumor mass in vivo over time compared with vehicle, lovastatin, and combination treatment. However, when combined with lovastatin, 13cRA enhanced the antiproliferative effect of lovastatin in vivo. The combination-treated mice showed slowest tumor growth of all groups with significantly slower tumor growth compared with the vehicle-treated mice and significantly smaller tumor sizes. Moreover, the combination-treated group displayed the smallest size of viable tumor mass and the slowest increase in viable tumor mass over time of all groups, with a significant difference compared with the vehicle- and 13cRA-treated group. The combination-treated tumors showed highest extent of necrosis, lowest median microvessel density and highest expression of α-smooth muscle actin. The combination of high microvessel density and low α-smooth muscle actin is a predictor of poor prognosis in other tumor entities. Therefore, this drug combination may be a well-tolerated novel therapeutic or preventive option for malignant PCC.

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