Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats.

Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging.

Cell-responsive hydrogel for encapsulation of vascular cells.

The in vitro potential of a synthetic matrix metalloproteinase (MMP)-responsive poly(ethylene glycol) (PEG)-based hydrogel as a bioactive co-encapsulation system for vascular cells and a small bioactive peptide, thymosin beta4 (Tbeta4), was examined. We show that the physical incorporation of Tbeta4 in this bioactive matrix creates a three-dimensional (3D) environment conducive for human umbilical vein endothelial cell (HUVEC) adhesion, survival, migration and organization. Gels with entrapped Tbeta4 increased the survival of HUVEC compared to gels without Tbeta4, and significantly up-regulated the endothelial genes vascular endothelial-cadherin and angiopoietin-2, whereas von Willebrand factor was significantly down-regulated.

Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG-hydrogel.

We show that synthetic three-dimensional (3D) matrix metalloproteinase (MMP)-sensitive poly(ethylene glycol) (PEG)-based hydrogels can direct differentiation of pluripotent cardioprogenitors, using P19 embryonal carcinoma (EC) cells as a model, along a cardiac lineage in vitro. In order to systematically probe 3D matrix effects on P19 EC differentiation, matrix elasticity, MMP-sensitivity and the concentration of a matrix-bound RGDSP peptide were modulated. Soft matrices (E=322+/-64.

Fate of undifferentiated mouse embryonic stem cells within the rat heart: role of myocardial infarction and immune suppression.

Abstract It has recently been suggested that the infarcted rat heart microenvironment could direct pluripotent mouse embryonic stem cells to differentiate into cardiomyocytes through an in situ paracrine action. To investigate whether the heart can function as a cardiogenic niche and confer an immune privilege to embryonic stem cells, we assessed the cardiac differentiation potential of undifferentiated mouse embryonic stem cells (mESC) injected into normal, acutely or chronically infarcted rat hearts. We found that mESC survival depended on immunosuppression both in normal and infarcted hearts.

Enhanced intimal thickening of expanded polytetrafluoroethylene grafts coated with fibrin or fibrin-releasing vascular endothelial growth factor in the pig carotid artery interposition model.

Objective: Intimal hyperplasia and surface thrombogenicity are major factors in the high failure rate of synthetic small-diameter bypass grafts. Vascular endothelial growth factor is a potent stimulus for endothelial growth, and its provision in a fibrin matrix coating at the luminal graft surface may hold a key to spontaneous graft endothelialization and improved graft patency.

Methods: Pigs underwent bilateral carotid artery interposition of expanded polytetrafluoroethylene grafts either impregnated with fibrin (n = 11)--engineered to locally release vascular endothelial growth factor121 (vascular endothelial growth factor-fibrin; n = 11)--or left uncoated (n = 12).

The Young's modulus of fetal preterm and term amniotic membranes.

Objective: To examine the Young's modulus of the human amniotic membranes, as well as its relationship to gestational age. To determine whether cellular and material-related parameters affect this modulus.

Study Design: In a prospective study at the Obstetric outpatient clinic of the University Hospital Zurich Young's modulus, thickness and mesenchymal:epithelial cell ratio of amniotic membranes of preterm (N=23) and term (N=40) placentae were examined.

Adult 'endothelial progenitor cells'. Renewing vasculature.

During embryogenesis, endothelial progenitor cells participate in the initial processes of primitive blood vessel formation (vasculogenesis). It has become evident that progenitors to vascular endothelial cells also exist in the adult. Endothelial progenitors normally reside in the adult bone marrow but may become mobilized into circulation by cytokine or angiogenic growth factor signals from the periphery, enter extravascular tissue, and promote de novo vessel formation by virtue of physically integrating into vessels and/or supplying growth factors (adult vasculogenesis).

Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity.

A number of vascular therapies could benefit from advanced methods for presentation of angiogenic growth factors, including growth of endothelium on small caliber vascular grafts and revascularization of ischemic tissue through induction of collateral vessels and microvessels. To explore methods to optimize the presentation and release of angiogenic factors in such applications in device integration and tissue repair, we studied three variant forms of vascular endothelial growth factor 121 (VEGF121), each with differential susceptibility to local cellular proteolytic activity, formulated within fibrin matrices. (1) The prototypic variant alpha2PI(1-8)-VEGF121 remains immobilized in fibrin matrices until its liberation by cell-associated enzymes, such as plasmin, that degrade the fibrin network [slow, cell-demanded release; J.

Immobilization of the enzyme beta-lactamase on biotin-derivatized poly(L-lysine)-g-poly(ethylene glycol)-coated sensor chips: a study on oriented attachment and surface activity by enzyme kinetics and in situ optical sensing.

Understanding the conformation, orientation, and specific activity of proteins bound to surfaces is crucial for the development and optimization of highly specific and sensitive biosensors. In this study, the very efficient enzyme beta-lactamase is used as a model protein. The wild-type form was genetically engineered by site-directed mutagenesis to introduce single cysteine residues on the surface of the enzyme.

Cardiac tissue engineering: regeneration of the wounded heart.

New solutions are needed to regenerate hearts damaged by myocardial infarction, to overcome bad prognosis of patients with heart failure, and to address the shortage of heart donors. In the past few years, cardiac tissue engineering has emerged as a new and ambitious approach that combines knowledge from material chemistry with cell biology and medicine. In this short review, we present an overview on the most promising materials and cell-therapy strategies used in the past few years for the regeneration of the wounded heart.

Atomic force microscope: a tool for studying ionophores.

The aim of the investigations was to show the analytical use of an atomic force microscopy (AFM) tip coated with an ion-selective membrane and to show that the ion-selective boundary potential is detectable as a force induced by ion-selective electrostatic interactions, which are more pronounced than double-layer forces. This new technique allows the area-specific ion exchange over boundaries to be displayed with a destruction-free technique by AFM in an aqueous buffer. From experiments with ISEs (ion-selective electrodes), a boundary potential for valinomycin was assumed to be established in close vicinity to a K+-releasing surface.