In Search of Living Valve Substitutes

Yacoub, Magdi H.

doi:10.1016/j.jacc.2015.07.007

Cited by 29 publications

(20 citation statements)

References 15 publications

(9 reference statements)

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“…15 Conceptually, this builds on breakthroughs, over the past 10 to 15 years, in the pre-clinical and clinical application of decellularized allo- and xenografts for heart valve repair and replacement, 16 including the limitations and challenges associated with the approach. 17 …”

Section: Fibroblasts and Adult Myocardial Homeostasismentioning

confidence: 99%

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

Gourdie

Dimmeler

Kohl

2016

Nat Rev Drug Discov

268

204

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Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development.

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Section: Fibroblasts and Adult Myocardial Homeostasismentioning

confidence: 99%

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

Gourdie

Dimmeler

Kohl

2016

Nat Rev Drug Discov

268

204

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“…It has been shown that integrins regulate proliferation, differentiation, and action of growth factors in other non-valve cell types (36)(37)(38). This observation has led to the concept that the extracellular matrix is able to instruct the cells that populate the valve via communication through integrins to intracellular signaling pathways (35,39). These cellmatrix connections also perform a key role in the transduction of mechanical signals to the cells.…”

Section: Diverse Functionality Of the Extracellular Matrixmentioning

confidence: 99%

Which Biological Properties of Heart Valves Are Relevant to Tissue Engineering?

Chester¹,

Grande‐Allen

2020

Front. Cardiovasc. Med.

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Over the last 20 years, the designs of tissue engineered heart valves have evolved considerably. An initial focus on replicating the mechanical and structural features of semilunar valves has expanded to endeavors to mimic the biological behavior of heart valve cells as well. Studies on the biology of heart valves have shown that the function and durability of native valves is underpinned by complex interactions between the valve cells, the extracellular matrix, and the mechanical environment in which heart valves function. The ability of valve interstitial cells to synthesize extracellular matrix proteins and remodeling enzymes and the protective mediators released by endothelial cells are key factors in the homeostasis of valve function. The extracellular matrix provides the mechanical strength and flexibility required for the valve to function, as well as communicating with the cells that are bound within. There are a number of regulatory mechanisms that influence valve function, which include neuronal mechanisms and the tight regulation of growth and angiogenic factors. Together, studies into valve biology have provided a blueprint for what a tissue engineered valve would need to be capable of, in order to truly match the function of the native valve. This review addresses the biological functions of heart valve cells, in addition to the influence of the cells' environment on this behavior and examines how well these functions are addressed within the current strategies for tissue engineering heart valves in vitro, in vivo, and in situ.

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“…In the past, we have used dura mater with apparently good results, but they are no longer available. Tissue engineering of patches or entire valves is an emerging area of surgical research (16). While not currently in use, such technologies will hopefully be available in the near future potentially improving outcomes at a lower cost.…”

Section: How To Repair the Rheumatic Aortic Valvementioning

confidence: 99%