Controlling the balance of endothelial cells (ECs) and smooth muscle cells (SMCs) in blood vessels is critically important to minimize the risk associated with vascular implants. Extracellular matrix (ECM) plays a key role in controlling the cellular balance, suggesting a promising source of cell-selective peptides. To obtain EC- or SMC-selective peptides, we start by highlighting sequence differences found among ECM molecules as enriched targets for cell-selective peptides. We explored the EC- or SMC-selective performance of tripeptides that are specifically enriched only in collagen type IV, but not in types I, II, III, and V. Collagen type IV was chosen since it is the major ECM in the basement membrane of blood vessels, which separates ECs and SMCs. Among 114 collagen type IV-derived tripeptides pre-screened from in silico analysis, 22 peptides (19%) were found to promote cell-selective adhesion, as determined by peptide array. One of the best performing EC-selective peptides (Cys-Ala-Gly (CAG)) was mixed into an electrospun fine-fiber, a vascular graft material, for practical application. Compared to unmodified fiber, the CAG containing fiber surface was found to enhance adhesion of ECs (+190%) while limiting SMCs (−20%). These results are not only consistent with the hypothesis of ECM as a source of cell selective peptides, but also suggest a new genre of EC- or SMC-selective peptides for tissue engineering applications. Collectively, these findings favorably support the screening approach used to discover new peptides for these purposes. Biotechnol. Bioeng.
submitted by carenniloagrast 2 years and 4 months ago
There is no effective therapy for advanced liver fibrosis. Angiotensin type 1 (AT1) receptor blockers attenuate liver fibrogenesis, yet their efficacy in reversing advanced fibrosis is unknown. We investigated whether the specific delivery of an AT1 receptor blocker to activated hepatic stellate ...
Pathologic intraocular neovascularization is a key component of many canine ophthalmic diseases such as uveitis, retinal detachment, intraocular neoplasms, and corneal perforation. The purpose of this study was to evaluate the structure of pre-iridal fibrovascular membranes (PIFMs) associated wit...
Fibroblasts are heterogeneous mesenchymal cells that play important roles in the production and maintenance of extracellular matrix. Although their heterogeneity is recognized, progenitor progeny relationships among fibroblasts and the factors that control fibroblast differentiation are poorly de...
A key mechanism for mesenchymal stem cells/bone marrow stromal cells (MSCs) to promote tissue repair is by secretion of soluble growth factors. Clinical application could therefore be optimized by a combination of cell and gene therapies, where MSCs are genetically modified to express higher leve...
In situvascular tissue engineering (TE) aims at regenerating vessels using implanted synthetic scaffolds. An envisioned strategy is to capture and differentiate progenitor cells from the bloodstream into the porous scaffold to initiate tissue formation. Among these cells are the endothelial colon...
Inhibition of the cannabinoid receptor CB1 (CB1-R) exerts numerous positive cardiovascular effects such as modulation of blood pressure, insulin sensitivity and serum lipid concentrations. However, direct vascular effects of CB1-R inhibition remain unclear. CB1-R expression was validated in vascu...
Mineralocorticoid receptor (MR) activation is proinflammatory and proatherogenic. Antagonism of MR improves survival in humans with congestive heart failure caused by atherosclerotic disease. In animal models, activation of MR exacerbates atherosclerosis. The enzyme 11β-hydroxysteroid dehydr...
The origin of the mesenchymal cells responsible for the intimal fibrosis in Systemic Sclerosis (SSc) has not been fully identified. Here, we investigated whether subendothelial mesenchymal cells may emerge through transdifferentiation of endothelial cells (EC) into myofibroblasts via endothelial-...
Wound healing generally induces an inflammatory response associated with tissue fibrosis in which activated macrophage and myofibroblast cells are primarily involved. Although this is known to be the underlying mechanism for scarring and various fibrotic pathologies, no effective intervention is ...
Cannabinoid receptor CB2 activation inhibits inflammatory proliferation and migration of vascular smooth muscle cells in vitro. The potential in vivo relevance of these findings is unclear. We performed carotid balloon distension injury in hypercholesterolemic apolipoprotein E knockout (ApoE&ndas...
