Matrix as an Interstitial Transport System

Abstract

T he extracellular space, or the interstitium, can be broadly divided into a fluid phase (water, electrolytes, nutrients, and some plasma proteins) and the extracellular matrix (ECM). In the heart, the ECM comprises structural proteins (primarily collagen types I and III) that form the fibrillar structure of the matrix; the basement membrane that forms an interface between the cardiomyocytes and the interstitial space as well as the molecules that mediate the cell-ECM connection; and the nonstructural proteins such as proteoglycans. Molecules traveling in the extracellular space come in contact with different ECM components, and these interactions determine the direction, speed, and distance of their transport, whereas the ECM can also provide a reservoir for several growth factors and cytokines. Moreover, the cell-ECM connection allows for transmission of signals across the cell membrane. Therefore, in addition to the classical role of ECM in providing structural support, it contributes to a multitude of intra-and extracellular events. Several thorough reviews have been published recently on the structural properties of the ECM and its remodeling in heart disease. [1][2][3] In this review, we will discuss less explored aspects of ECM function, such as its conductivity in extracellular transportation, its role in cell-cell interactions, and different modes of cell-cell communication through the extracellular space.

Engineered heart slices for electrophysiological and contractile studies

“…For example, the ECM can retain growth factors and mediate the availability of these and other signaling molecules [21]. Additionally, cell function is affected by integrin-matrix binding and other biomechanical pathways [21,22].…”

“…For example, the ECM can retain growth factors and mediate the availability of these and other signaling molecules [21]. Additionally, cell function is affected by integrin-matrix binding and other biomechanical pathways [21,22]. Although the degree of retention of different ECM constituents varies with the decellularization method [14], the complex protein composition of native ECM is largely retained following decellularization, which is an advantage over scaffolds that provide only one or a small number of ECM proteins, since cell growth depends on a variety of ECM proteins [8,23].…”

Myocardial matrix metalloproteinase-2: inside out and upside down

“…While the myocardial ECM is an interstitial transport system, the tracks leading from the ECM continue intracellularly to provide a continuum from the nucleus of one cell to the nucleus of another. [80] Another area of investigation involves the different intracellular MMP-2 isoforms, the effects of their post-translational modifications, and their unique roles in cardiac pathologies. The development of MMP-2 specific inhibitors, particularly for intracellular isoforms, is highly encouraged.…”

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

“…The vast potential of miRNA therapies for tissue repair and RM has been extensively reviewed in the last few years in either general terms [25,141] or with more focused applications in mind such as bone/orthopedics, [104,142] angiogenesis, [143] the cardiovascular system, [144] or skin, [145] but the area of scaffold-based miRNA delivery in RM is still relatively in its infancy. To date, reports on scaffold-mediated miRNA delivery have focused more on specific areas of regenerative medicine including osteogenesis and bone repair as well as the cardiovascular arena (Table 2), but this progress report aims to give a broader overview encompassing a variety of areas of RM.…”