Bovine mitral valve organ culture: Role of interstitial cells in repair of valvular injury

Lester, Wanda M.

doi:10.1016/0022-2828(92)91158-2

Cited by 29 publications

(25 citation statements)

References 23 publications

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“…1a-c; see Franke et al 1979a, b;Herrmann et al 2007). Remarkably, most of these VICs in situ were not closely packed but appeared evenly dispersed, so that the individual VIC for the most part appeared to be surrounded and thus separated by matrix, except for a few cell processes protruding into the extracellular matrix (ECM; see also Kühnel 1966a, b;Filip et al 1986;Lester et al 1988Lester et al , 1992. In addition, we regularly noted a minor VIC population that was also positive for sm-α-actin and often appeared to be enriched in a conspicuous subcortical valve layer extending with some distance parallel to the Fig.…”

Section: Resultsmentioning

confidence: 93%

“…This also holds for cardiac valves and their major cell type, the valvular interstitial cells (VICs), in spite of numerous projects on valve replacement and the design of engineered artificial valves (see Cebotari et al 2006;Lichtenberg et al 2006; for a recent review, see Schoen 2008). However, whereas many studies have dealt with some selected cytoplasmic structures and proteins of VICs in situ or in culture (see Lester et al 1988Lester et al , 1992Messier et al 1994;Icardo and Colvee 1995;Mulholland and Gotlieb 1996;Taylor et al 2000Taylor et al , 2003Bertipaglia et al 2003;Cimini et al 2003;Schenke-Leyland et al 2004;Yperman et al 2004;Latif et al 2005aLatif et al , b, 2006Latif et al , 2007Blevins et al 2006;Brand et al 2006;Chester and Taylor 2007;Pho et al 2008), little is known of the molecular composition of their cell-cell junctions. Therefore, we provide a general cell-biological basis for the design of valve replacement structures and have determined the molecular ensemble of the AJs that connect VICs and thus establish the architecture of the VIC junctions.…”

Section: Introductionmentioning

confidence: 97%

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Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture

et al. 2009

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Remarkable efforts have recently been made in the tissue engineering of heart valves to improve the results of valve transplantations and replacements, including the design of artificial valves. However, knowledge of the cell and molecular biology of valves and, specifically, of valvular interstitial cells (VICs) remains limited. Therefore, our aim has been to determine and localize the molecules forming the adhering junctions (AJs) that connect VICs in situ and in cell culture. Using biochemical and immunolocalization methods at the light- and electron-microscopic levels, we have identified, in man, cow, sheep and rat, the components of VIC-connecting AJs in situ and in cell culture. These AJs contain, in addition to the transmembrane glycoproteins N-cadherin and cadherin-11, the typical plaque proteins alpha- and beta-catenin as well as plakoglobin and p120, together with minor amounts of protein p0071, i.e. a total of five plaque proteins of the armadillo family. While we can exclude the occurrence of desmogleins, desmocollins and desmoplakin, we have noted with surprise that AJs of VICs in cell cultures, but not those growing in the valve tissue, contain substantial amounts of the desmosomal plaque protein, plakophilin-2. Clusters of AJs occur not only on the main VIC cell bodies but are also found widely dispersed on their long filopodia thus forming, in the tissue, a meshwork that, together with filopodial attachments to paracrystalline collagen fiber bundles, establishes a three-dimensional suprastructure, the role of which is discussed with respect to valve formation, regeneration and function.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 97%

Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture

et al. 2009

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“…12 It is also present in several heart valverelated diseases (eg, calcific aortic stenosis, 18,19 mitral valve prolapse, 20,21 and Marfan syndrome). 22 By using a well-characterized wound model, 11 we also reported an up-regulation of TGF-␤ at the in vitro wound edge. The exogenous addition of TGF-␤ further activates the VICs along the wound edge and stimulates their proliferation to enhance wound closure within the first 24 hours after wounding.…”

mentioning

confidence: 73%

“…2,4,6 -8 Like other myofibroblasts, 9 VICs regulate wound repair, as demonstrated by the increased number and enhanced production of ECM components, both in diseased valves and in in vitro wound models. 10,11 Thus, understanding the regulation of the biological and pathobiological features of VICs is essential for understanding the pathogenesis of heart valve diseases.…”

mentioning

confidence: 99%

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

Gotlieb

2011

The American Journal of Pathology

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Although valve interstitial cell (VIC) growth is an essential feature of injured and diseased valves, the regulation of VIC growth is poorly understood. Transforming growth factor (TGF)-␤ promotes VIC proliferation in early-stage wound repair; thus, herein, we tested the hypothesis that TGF-␤ regulates VIC proliferation under normal nonwound conditions using low-density porcine VIC monolayers. Cell numbers were counted during a 10-day period, whereas proliferation and apoptosis were quantified by bromodeoxyuridine staining and TUNEL, respectively. The extent of retinoblastoma protein phosphorylation and expression of cyclin D1, CDK 4, and p27 were compared using Western blot analysis. Adhesion was quantified using a trypsin adhesion assay, and morphological change was demonstrated by immunofluorescence localization of ␣-smooth muscle actin and vinculin. TGF-␤-treated VICs were rhomboid; significantly decreased in number, proliferation, and retinoblastoma protein phosphorylation; and concomitantly had decreased expression of cyclin D1/CDK4 and increased expression of p27. TGF-␤-treated VICs adhered better to substratum and had more vinculin plaques and ␣-smooth muscle actin stress fibers than did controls. Thus, the regulation of VIC growth by TGF-␤ is context dependent. TGF-␤ prevents excessive heart valve growth under normal physiological conditions while it promotes cell proliferation in the early stages of repair, when increased VICs are required.

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“…However, the materials that are commonly used lack growth potential, and long-term results have revealed several material-related failures, such as stenosis, thromboembolization, calcium deposition, and risk of infection (13). Previously, organ cultures such as heart valves were developed to study the biological characteristics of native aortic valves cultured in vitro and understand fundamental valve pathogenesis (14)(15)(16)(17). An organ culture maintains cells within their na- tive microstructural environment, and thus offers greater potential.…”

Section: Discussionmentioning

confidence: 99%

The Porcine Aortic Tissue Culture System in vitro for Stem Cell Research

Kim

Yang

et al. 2011

Int J Stem Cells

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Background and Objectives: Due to the shortage of human donors for transplantation, the use of animal organs for xenotransplantation has come into great interest. Xeno-derived vessels and cardiac valves would be possible alternatives for the patient suffering from cardiovascular diseases. Therefore, we established in vitro culture system of a porcine vessel that could be helpful for the research of xenograft and stem cell research. Methods and Results: We primarily isolated porcine thoracic aorta, cultured square-shaped pieces up to 17 days and analyzed its morphology and characters. The endothelial cells were primarily isolated from cultured porcine aortic pieces and their morphology, function and character were analyzed in order to confirm them as endothelial cells at day 3, 4, 8, 10 and 17. Even at day 17, the morphology exhibited the intact endothelial layer as well as specifically expressed CD31 and von Willebrand factor. The morphology of primarily isolated cells from cultured tissues was identical as an endothelial cell. By flow cytometry analysis, more than 80% of the isolated cells expressed CD31 and up to 80% took up acetyl low density lipoprotein (ac-LDL) until day 10 of tissue culture period even though it decreased to about 50% at day 17 that means they not only showed typical endothelial cell characters but also functioned properly. Conclusions: We successfully established and optimized a porcine vascular tissue in vitro culture system that could be a valuable model for in vitro study of xenotransplantation and stem cell research.

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Bovine mitral valve organ culture: Role of interstitial cells in repair of valvular injury

Cited by 29 publications

References 23 publications

Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture

Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

The Porcine Aortic Tissue Culture System in vitro for Stem Cell Research

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