Macrophage-extracellular matrix interactions: Perspectives for tissue engineered heart valve remodeling

Abstract

In situ heart valve tissue engineering approaches have been proposed as promising strategies to overcome the limitations of current heart valve replacements. Tissue engineered heart valves (TEHVs) generated from in vitro grown tissue engineered matrices (TEMs) aim at mimicking the microenvironmental cues from the extracellular matrix (ECM) to favor integration and remodeling of the implant. A key role of the ECM is to provide mechanical support to and attract host cells into the construct. Additionally, each ECM component plays a critical role in regulating cell adhesion, growth, migration, and differentiation potential. Importantly, the immune response to the implanted TEHV is also modulated biophysically via macrophage-ECM protein interactions. Therefore, the aim of this review is to summarize what is currently known about the interactions and signaling networks occurring between ECM proteins and macrophages, and how these interactions may impact the long-term in situ remodeling outcomes of TEMs. First, we provide an overview of in situ tissue engineering approaches and their clinical relevance, followed by a discussion on the fundamentals of the remodeling cascades. We then focus on the role of circulation-derived and resident tissue macrophages, with particular emphasis on the ramifications that ECM proteins and peptides may have in regulating the host immune response. Finally, the relevance of these findings for heart valve tissue engineering applications is discussed.

Development of an iPSC-derived tissue-resident macrophage-based platform for the in vitro immunocompatibility assessment of human tissue engineered matrices

“…The reported polarization is in alignment with peripheral blood-derived macrophages from literature 12 , 31 , 45 , 48 . Macrophage polarization states are crucial for ECM-based hTEM remodeling in vivo 49 . Even though the polarization response agrees with literature in the up-regulation of general polarization markers (e.g., IL-6, IL-1β, TNF-α, IL-8 and MCP-1) 45 , it has not been employed for a functional evaluation of immunocompatibility.…”

“…In general, it has been recently reviewed that ECM composition has indeed the potential to affect the initial macrophage infiltration and polarization 49 . Our hTEM proteomic composition has been extensively analyzed in multiscale characterization study 9 .…”

Development of an iPSC-derived resident tissue macrophage-based platform for the in vitro immunocompatibility assessment of human tissue engineered matrices

“…Macrophage polarization states are crucial for ECM-based hTEM remodeling in vivo 55 . Even though the polarization response agrees with literature in the up-regulation of general polarization markers (e.g., IL-6, IL-1β, TNF-α, IL-8 and MCP-1) 51 , it has not been employed for a functional evaluation of immunocompatibility.…”

Cardiovascular Protection with a Long-Acting GLP-1 Receptor Agonist Liraglutide: An Experimental Update

“…Maladaptive cardiac remodeling refers to molecular, cellular and interstitial alterations in the myocardium, leading to histopathological changes in the structure, shape and function of the heart [ 6 , 7 , 8 ]. This process is associated with a poor prognosis due to ventricular dysfunction.…”

“…The mechanisms of action that have been proposed are the generation of proinflammatory mediators, reduction of endothelial nitric oxide synthase (eNOS) release, upregulation of endothelial adhesion molecules, attenuation of endothelium-dependent vasorelaxation and augmentation of extravascular cell migration [ 3 , 4 ]. In heart failure, morphological changes, such as cardiac hypertrophy and fibrosis, cause progressive loss of cardiomyocytes and deterioration of ventricular function through an extracellular matrix remodeling process [ 5 , 6 ] that includes extravascular infiltration of macrophages, differentiation of myofibroblasts, activation of TGFβ/Smads-mediated signaling and augmentation of collagen synthesis [ 7 ].…”