scholarly journals Valvular endothelial cells are recruited into interstitial cells for heart valve homeostasis

2017 ◽  
Vol 145 ◽  
pp. S150
Author(s):  
Kin Ming Kwan ◽  
Pak Lun Baggio Liu ◽  
Ka Kui Tong
Keyword(s):  
Endothelial Cells ◽  
Heart Valve ◽  
Interstitial Cells

scholarly journals Molecular and functional characteristics of heart-valve interstitial cells

2007 ◽  
Vol 362 (1484) ◽  
pp. 1437-1443 ◽  
Author(s):  
Adrian H Chester ◽  
Patricia M Taylor
Keyword(s):  
Endothelial Cells ◽  
Heart Valve ◽  
Heart Valves ◽  
Cell Types ◽  
Interstitial Cells ◽  
Individual Characteristics ◽  
The Body ◽  
Integral Role ◽  
Valve Function ◽  
And Function

The cells that reside within valve cusps play an integral role in the durability and function of heart valves. There are principally two types of cells found in cusp tissue: the endothelial cells that cover the surface of the cusps and the interstitial cells (ICs) that form a network within the extracellular matrix (ECM) within the body of the cusp. Both cell types exhibit unique functions that are unlike those of other endothelial and ICs found throughout the body. The valve ICs express a complex pattern of cell-surface, cytoskeletal and muscle proteins. They are able to bind to, and communicate with, each other and the ECM. The endothelial cells on the outflow and inflow surfaces of the valve differ from one another. Their individual characteristics and functions reflect the fact that they are exposed to separate patterns of flow and pressure. In addition to providing a structural role in the valve, it is now known that the biological function of valve cells is important in maintaining the integrity of the cusps and the optimum function of the valve. In response to inappropriate stimuli, valve interstitial and endothelial cells may also participate in processes that lead to valve degeneration and calcification. Understanding the complex biology of valve interstitial and endothelial cells is an important requirement in elucidating the mechanisms that regulate valve function in health and disease, as well as setting a benchmark for the function of cells that may be used to tissue engineer a heart valve.

Abstract 319: Tnf-α and Il-1β Decrease Myofibroblast Differentiation in 3d-cultured Mitral Valve Interstitial Cells

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Amadeus Zhu ◽  
Jane Grande-Allen
Keyword(s):  
Smooth Muscle ◽  
Mitral Valve ◽  
Heart Valve ◽  
Interstitial Cells ◽  
Valve Disease ◽  
Tissue Type ◽  
Heart Valve Diseases ◽  
Valve Interstitial Cells ◽  
Tnf Α ◽  
Valve Diseases

Background: Fibrosis contributes to many heart valve diseases such as calcific aortic valve disease, rheumatic heart disease, and secondary mitral regurgitation. Heart valve leaflets are populated by quiescent, fibroblast-like valve interstitial cells (VICs). During fibrosis, VICs differentiate into activated, myofibroblast-like cells that adversely remodel the extracellular matrix. Activated VICs overexpress α-smooth muscle actin (ACTA2/αSMA) and smooth muscle 22-α (TAGLN/SM22α) and display increased contractility. Tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) have been reported to either promote or inhibit fibrosis, depending on tissue type. Understanding how TNF-α and IL-1β affect VIC activation in the mitral valve of the heart could enable development of pharmaceutical treatments for heart valve diseases, which are currently managed surgically. Methods: To avoid artifactual activation on tissue culture plastic, VICs were encapsulated in biomimetic scaffolds consisting of polyethylene glycol (4% w/v) functionalized with protease-degradable (GGGPQGIWGQGK) and integrin-binding (RGDS) peptides. These 3D cultures were treated with 10 ng/ml TNF-α, 10 ng/ml IL-1β, or vehicle for 2 days in low-serum (1%) media. RNA and protein were measured via qRT-PCR, western blotting, and immunostaining. To measure contractility, VICs were encapsulated in collagen I (2.5 mg/ml) gels and allowed to contract freely for 2 days. Results: TNF-α and IL-1β significantly decreased RNA expression of ACTA2 (TNF-α: -91±6%, IL-1β: -99±1% change vs. vehicle) and TAGLN (TNF-α: -77±9%, IL-1β: -93±1% change). TNF-α and IL-1β also significantly decreased αSMA protein expression (TNF-α: -76±11%, IL-1β: -91±5% change) and the percentage of αSMA-positive cells (vehicle: 21±3%, TNF-α: 13±2%, IL-1β: 13±5% positive). Finally, TNF-α and IL-1β attenuated VIC-mediated collagen gel contraction (vehicle: 81±7%, TNF-α: 71±3%, IL-1β: 61±4% contraction). Conclusions: TNF-α and IL-1β decrease VIC activation in a 3D culture model of the mitral valve. These results reveal novel pathway targets for reducing fibrosis during mitral valve disease. Future work will use this model to study the downstream signaling events that drive VIC de-activation.

scholarly journals Valve Interstitial Cells: The Key to Understanding the Pathophysiology of Heart Valve Calcification

2017 ◽  
Vol 6 (9) ◽  
Author(s):  
Arkady Rutkovskiy ◽  
Anna Malashicheva ◽  
Gareth Sullivan ◽  
Maria Bogdanova ◽  
Anna Kostareva ◽  
...  
Keyword(s):  
Heart Valve ◽  
Interstitial Cells ◽  
Valve Calcification ◽  
Valve Interstitial Cells

Regeneration ability of valvular interstitial cells from diseased heart valve leaflets

RSC Advances ◽  
2016 ◽  
Vol 6 (115) ◽  
pp. 113859-113870 ◽  
Author(s):  
Soumen Jana ◽  
Rebecca Hennessy ◽  
Federico Franchi ◽  
Melissa Young ◽  
Ryan Hennessy ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Heart Valve ◽  
Interstitial Cells ◽  
Regeneration Ability ◽  
Valvular Interstitial Cells ◽  
Aortic Valve Leaflets ◽  
Ability To Regenerate

Valvular interstitial cells from diseased aortic valve leaflets show their ability to regenerate–to proliferate and grow, to express appropriate genes and to deposit suitable proteins–in a non-degenerative nanofibrous substrate.

scholarly journals Reendothelialization of Human Heart Valve Neoscaffolds Using Umbilical Cord-Derived Endothelial Cells

2013 ◽  
Vol 77 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Alexander Weymann ◽  
Bastian Schmack ◽  
Takayuki Okada ◽  
P^|^aacute;l So^|^oacute;s ◽  
Roland Ist^|^oacute;k ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Cord ◽  
Heart Valve ◽  
Human Heart

scholarly journals Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

2021 ◽  
Vol 8 ◽  
Author(s):  
Ionela Movileanu ◽  
Marius Harpa ◽  
Hussam Al Hussein ◽  
Lucian Harceaga ◽  
Alexandru Chertes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Cell Fate ◽  
Heart Valve ◽  
Pediatric Patients ◽  
Living Tissue ◽  
Congenital Diseases ◽  
Challenges And Opportunities

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries.Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls.Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold.Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology.

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