Molecular and functional changes in voltage-gated Na⁺ channels in cardiomyocytes during mouse embryogenesis.

Background: Embryonic cardiomyocytes undergo profound changes in their electrophysiological properties during development. However, the molecular and functional changes in Na⁺ channel during cardiogenesis are not yet fully explained.

Methods And Results: To study the functional changes in the Na⁺ channel during cardiogenesis, Na⁺ currents were recorded in the early (EDS) and late (LDS) developmental stages of cardiomyocytes in embryonic mice.

Ca(v)2.3 Ca2+ channel interacts with the G1-subunit of V-ATPase.

Background: Calcium channels are essential in coupling action potential to signal transduction in cells. There are several types of calcium channels, which can be pharmacologically classified as L-, N-, P/Q-, R- and T-type. But molecular basis of R-type channels is less clearly understood compared the other channel types.

Specific gene signatures and pathways in mesodermal cells and their derivatives derived from embryonic stem cells.

The vertebrate early stage embryo is consisting of the three primary germ layers ectoderm, mesoderm and endoderm, from which all organ tissues are developed. During early embryonic development, mesodermal cells become sequentially determined to more precisely defined cell types including muscle, heart, vasculature, blood, kidney, gonads, dermis and cartilage. How the prospective mesodermal cells integrate the various signals they receive and how they resolve this information to regulate their morphogenetic behavior and cell fate decisions is largely unknown.

Imaging herpes simplex virus type 1 amplicon vector-mediated gene expression in human glioma spheroids.

Vectors derived from herpes simplex virus type 1 (HSV-1) have great potential for transducing therapeutic genes into the central nervous system; however, inefficient distribution of vector particles in vivo may limit their therapeutic potential in patients with gliomas. This study was performed to investigate the extent of HSV-1 amplicon vector-mediated gene expression in a three-dimensional glioma model of multicellular spheroids by imaging highly infectious HSV-1 virions expressing green fluorescent protein (HSV-GFP). After infection or microscopy-guided vector injection of glioma spheroids at various spheroid sizes, injection pressures and injection times, the extent of HSV-1 vector-mediated gene expression was investigated via laser scanning microscopy.

Concise review: induced pluripotent stem cells and lineage reprogramming: prospects for bone regeneration.

Bone tissue for transplantation therapies is in high demand in clinics. Osteodegenerative diseases, in particular, osteoporosis and osteoarthritis, represent serious public health issues affecting a respectable proportion of the elderly population. Furthermore, congenital indispositions from the spectrum of craniofacial malformations such as cleft palates and systemic disorders including osteogenesis imperfecta are further increasing the need for bone tissue.

Effects of cryopreservation on the transcriptome of human embryonic stem cells after thawing and culturing.

Human embryonic stem cells (hESCs) can be propagated indefinitely in vitro in an undifferentiated pluripotent state, can differentiate into derivatives of all three germ layers and are of considerable interest for applications in regenerative medicine. Clinical application of hESCs, however, requires reliable protocols for cryopreservation. Current protocols for cryopreservation of hESCs suffer from low recovery rates of hESCs and loss of pluripotency after thawing.

Extract derived from rat brains in the acute phase following traumatic brain injury impairs survival of undifferentiated stem cells and induces rapid differentiation of surviving cells.

Dramatic cerebral responses following brain injury (TBI) comprise inflammation, cell death, and modulation of trophic factor release. These cerebral modulations might induce and/or attenuate acute neuronal damage. Here, we investigated the effect of tissue extract derived from healthy (HBE) or injured rat brain (TBE) on the differentiation of cultured embryonic stem cells in vitro.

Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation.

Background And Purpose: Teratogenic substances induce adverse effects during the development of the embryo. Multilineage differentiation of human embryonic stem cells (hESCs) mimics the development of the embryo in vitro. Here, we propose a transcriptomic approach in hESCs for monitoring specific toxic effects of compounds as an alternative to traditional time-consuming and cost-intensive in vivo tests requiring large numbers of animals.

Biological and physicochemical characterization of a serum- and xeno-free chemically defined cryopreservation procedure for adult human progenitor cells.

While therapeutic cell transplantations using progenitor cells are increasingly evolving towards phase I and II clinical trials and chemically defined cell culture is established, standardization in biobanking is still in the stage of infancy. In this study, the EU FP6-funded CRYSTAL (CRYo-banking of Stem cells for human Therapeutic AppLication) consortium aimed to validate novel Standard Operating Procedures (SOPs) to perform and validate xeno-free and chemically defined cryopreservation of human progenitor cells and to reduce the amount of the potentially toxic cryoprotectant additive (CPA) dimethyl sulfoxide (DMSO). To achieve this goal, three human adult progenitor and stem cell populations-umbilical cord blood (UCB)-derived erythroid cells (UCB-ECs), UCB-derived endothelial colony forming cells (UCB-ECFCs), and adipose tissue (AT)-derived mesenchymal stromal cells (AT-MSCs)-were cryopreserved in chemically defined medium supplemented with 10% or 5% DMSO.

Fibroblasts support functional integration of purified embryonic stem cell-derived cardiomyocytes into avital myocardial tissue.

Transplantation of purified pluripotent stem cell-derived cardiomyocytes into damaged myocardium might become a therapy to improve contractile function after myocardial infarction. However, engraftment remains problematic. Aim of this study was to investigate whether murine embryonic fibroblasts (MEFs) support the functional integration of purified embryonic stem cell-derived cardiomyocytes (ES-CMs).

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals.

Although myocyte cell transplantation studies have suggested a promising therapeutic potential for myocardial infarction, a major obstacle to the development of clinical therapies for myocardial repair is the difficulties associated with obtaining relatively homogeneous ventricular myocytes for transplantation. Human embryonic stem cells (hESCs) are a promising source of cardiomyocytes. Here we report that retinoid signaling regulates the fate specification of atrial versus ventricular myocytes during cardiac differentiation of hESCs.

Direct contact of umbilical cord blood endothelial progenitors with living cardiac tissue is a requirement for vascular tube-like structures formation.

The umbilical cord blood derived endothelial progenitor cells (EPCs) contribute to vascular regeneration in experimental models of ischaemia. However, their ability to participate in cardiovascular tissue restoration has not been elucidated yet. We employed a novel coculture system to investigate whether human EPCs have the capacity to integrate into living and ischaemic cardiac tissue, and participate to neovascularization.

Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C.

Aim: To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I(Ca,L)) in rat ventricular myocytes.

Methods: The whole-cell patch-clamp techniques were used to record I(Ca,L) in rat ventricular myocytes.

Results: Hyposmotic challenge(∼220 mosmol/L) induced biphasic changes of I(Ca,L), a transient increase followed by a sustained decrease.

Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.

Background: Functional and molecular integrity of cardiomyocytes (CMs) derived from induced pluripotent stem (iPS) cells is essential for their use in tissue repair, disease modelling and drug screening. In this study we compared global transcriptomes of beating clusters (BCs) microdissected from differentiating human iPS cells and embryonic stem (ES) cells.

Results: Hierarchical clustering and principal component analysis revealed that iPS-BCs and ES-BCs cluster together, are similarly enriched for cardiospecific genes and differ in expression of only 1.

Functional characterization of inward rectifier potassium ion channel in murine fetal ventricular cardiomyocytes.

Aims: Previous studies have shown the dramatic changes in electrical properties of murine fetal cardiomyocytes, while details on inward rectifier potassium current (IK1) are still seldom discussed. Thus we aimed to characterize the functional expression and functional role of IK1 in murine fetal ventricular cardiomyocytes.

Methods: Whole cell patch clamp was applied to investigate the electrophysiological properties of IK1.

Induced pluripotent stem cells: a new approach for physiological research.

The generation of induced pluripotent stem (iPS) cells by controlled delivery of reprogramming factors enables the derivation of pluripotent cells from a variety of somatic cell types. Patient-tailored iPS cells remove the major roadblock of immune rejection for clinical applications associated with the use of human embryonic stem (hES) cells. Beside therapeutic issues, iPS cell technology opens the door for broader research on human pluripotent cells because ethical limitations are lifted with iPS cells compared to hES cells.

Analyzing murine electrocardiogram with PhysioToolkit.

Quantitative electrocardiogram (ECG) analysis is a very important tool in cardiovascular and neuroedocrine research. It is useful in clinical trials with human beings, as well as in animals such as rabbits, rats, and mice, for example, in studying knockout models. The species of interest differ in their typical baseline heart rate and therefore in the sampling rate in ECG detection.

Isolation and functional characterization of alpha-smooth muscle actin expressing cardiomyocytes from embryonic stem cells.

Early mammalian heart development is characterized by transient expression of alpha-smooth muscle actin (Acta2). To date, cardiomyocytes expressing Acta2 in the early stages of in vivo development have not been characterized. To functionally characterize Acta2-expressing cardiomyocytes, we used a transgenic ES cell line expressing both the puromycin acetyl transferase (Pac) and enhanced green fluorescent protein (EGFP) cassettes under the control of the Acta2 promoter.

Electrophysiological basis of the first heart beats.

Aims: Earlier studies on cardiac pacemaker activity were inconclusive regarding the electrophysiological mechanism(s) of first electrical activity generation during cardiac development. We therefore aimed to investigate the role of ion channels in action potential (AP) formation and pacemaker activity during very early murine heart development (E8.5).

The aging heart: changes in the pharmacodynamic electrophysiological response to verapamil in aged rabbit hearts.

The aim of this study was to investigate whether the L-type calcium current (I(Ca.L)) may be altered in aged hearts and whether the classical calcium antagonist verapamil may exhibit altered pharmacological profile in aged hearts. We examined male New Zealand rabbits aged either 6 months or 26 months.

WITHDRAWN: Capsaicin inhibits beta-adrenergically-activated Na(+) current through endogenous calcineurin in cardiac myocytes.

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.

Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicity testing.

Developmental neurotoxicity (DNT) is a serious concern for environmental chemicals, as well as for food and drug constituents. Animal-based DNT models have relatively low sensitivity, and they are burdened by high work-load, cost and animal ethics. Murine embryonic stem cells (mESC) recapitulate several critical processes involved in the development of the nervous system if they are induced to differentiate into neural cells.

Effect of ZnCl2 and chelation of zinc ions by N,N-diethyldithiocarbamate (DEDTC) on the ERG b-wave amplitude from the isolated superfused vertebrate retina.

Purpose: NiCl(2) (15 microM) enhances the ERG b-wave amplitude of vertebrate retina, up to 1.5-fold by blocking E/R-type voltage-gated Ca(2+) channels, which is mediated by blocking the release of GABA onto ionotropic GABA-A and GABA-C receptors. In vivo, it is likely that zinc, rather than nickel ions, may be involved in the modulation of retinal signalling.