Key Roles of RGD-Recognizing Integrins During Cardiac Development, on Cardiac Cells, and After Myocardial Infarction

Possible Treatment of Myocardial Infarct Based on Tissue Engineering Using a Cellularized Solid Collagen Scaffold Functionalized with Arg-Glyc-Asp (RGD) Peptide

“…This observation has been confirmed by another research group, but in their experiments, the MSCs in collagen scaffolds are still associated with Matrigel™ [54]. The RGD peptide is also known to enhance angiogenesis in the presence of endothelial cell progenitors [23] and thus may also facilitate construct survival and functionality upon implantation. We anticipate that the functionalization of the collagen polymers used for making 3D environments for epicardial or intramyocardial cell delivery may well be improved with the RGD peptide that is present, but not functional, on native collagen [29,48].…”

“…Integrins that recognize the RGD motif have been shown to play a key role during cardiac development [18], pressure overload [19] and after MI [20][21][22] (for review [23]). After infarction, cells involved in the regenerative process are in the epicardial layer [24] and may thus be easier to treat with an epicardial therapy if available.…”

“…After infarction, cells involved in the regenerative process are in the epicardial layer [24] and may thus be easier to treat with an epicardial therapy if available. The interaction of regenerative cells with the local RGD motif of fibronectin has been shown to be essential with respect to their functionality and regenerative capacity [21,23]. Animal studies have shown that cellular engraftment is substantially higher if the cells are transferred as a contractile tissue structure rather than via free cell injections or infusions [9].…”

“…Animal studies have shown that cellular engraftment is substantially higher if the cells are transferred as a contractile tissue structure rather than via free cell injections or infusions [9]. Three-dimensional cultures have been shown to enhance cell ECM interactions through integrins and intercellular cell-cell interactions [23]. Associating cells with 3D scaffolds is the most promising way to improve cellular transplantation, especially if the cell-containing preparations are applied onto the epicardium instead of being intramyocardially injected [25][26][27][28][29].…”

“…Nowadays, the most promising cell types for cell therapy are multipotent human mesenchymal stem cells and resident cardiac stem cell preparations, such as "Cardiospheres" isolated from heart biopsies and embryonic cells: iPS-CM or ES-CM [30]. The crucial role of integrins with regard to therapeutic cardiac cells has been well documented (for review [23]). It has been shown that the present association of human angiogenic progenitor cells, isolated from blood with an injectable collagen type I, enhances their therapeutic effect in the context of an ischemic heart model by enhancing interactions with integrins α5 for fibronectin and α2β1 for collagen on these cells [32].…”