Biomaterializing the promise of cardiac tissue engineering.

During an average individual's lifespan, the human heart pumps nearly 200 million liters of blood delivered by approximately 3 billion heartbeats. Therefore, it is not surprising that native myocardium under this incredible demand is extraordinarily complex, both structurally and functionally. As a result, successful engineering of adult-mimetic functional cardiac tissues is likely to require utilization of highly specialized biomaterials representative of the native extracellular microenvironment.

Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells.

Our knowledge of pluripotent stem cell biology has advanced considerably in the past four decades, but it has yet to deliver on the great promise of regenerative medicine. The slow progress can be mainly attributed to our incomplete understanding of the complex biologic processes regulating the dynamic developmental pathways from pluripotency to fully-differentiated states of functional somatic cells. Much of the difficulty arises from our lack of specific tools to query, or manipulate, the molecular scale circuitry on both single-cell and organismal levels.

Stem Cell Surface Marker Expression Defines Late Stages of Reprogramming to Pluripotency in Human Fibroblasts.

Unlabelled: Our current understanding of the induction of pluripotency by defined factors indicates that this process occurs in discrete stages characterized by specific alterations in the cellular transcriptome and epigenome. However, the final phase of the reprogramming process is incompletely understood. We sought to generate tools to characterize the transition to a fully reprogramed state.

Comparison of reprogramming efficiency between transduction of reprogramming factors, cell-cell fusion, and cytoplast fusion.

Reprogramming human somatic cells into pluripotent cells opens up new possibilities for transplantation therapy, the study of disease, and drug screening. In addition to somatic cell nuclear transfer, several approaches to reprogramming human cells have been reported: transduction of defined transcription factors to generate induced pluripotent stem cell (iPSC), human embryonic stem cell (hESC)-somatic cell fusion, and hESC cytoplast-somatic cell fusion or exposure to extracts of hESC. Here, we optimized techniques for hESC-human fibroblast fusion and enucleation and cytoplast fusion, and then compared the reprogramming efficiency between iPSC generation, cell-fusion and cytoplast-fusion.

Current technology for the derivation of pluripotent stem cell lines from human embryos.

Technology for the derivation, propagation, and characterization of pluripotent stem cell lines from the human embryo has undergone considerable refinement and improvement since the first published description of human embryonic stem cells in 1998. In particular, there has been extensive effort to optimize protocols and develop defined culture systems with a view toward future clinical applications of embryonic stem cell-derived products. Here, we review the current status of methodology for human embryonic stem cell derivation and culture, and we highlight the challenges that remain for workers in the field.

Manipulation of small-molecule inhibitory kinetics modulates MCH-R1 function.

The capacity of novel benzopyridazinone-based antagonists to inhibit MCH-R1 function, relative to their affinity for the receptor, has been investigated. Three compounds that differ by the addition of either a chlorine atom, or trifluoromethyl group, have nearly identical receptor affinities; however their abilities to inhibit receptor elicited signaling events, measured as a function of time, are dramatically altered. Both the chlorinated and trifluoromethyl modified compounds have a very slow on-rate to maximal functional inhibition relative to the unmodified base compound.

Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors.

Indiplon (NBI 34060) is a novel pyrazolopyrimidine currently in development for the treatment of insomnia. We have previously shown that indiplon exhibits high-affinity binding to native GABA(A) receptors from rat brain and acts as a positive allosteric modulator of GABA(A) receptor currents in cultured rat neurons (Sullivan et al., 2004).

Role of the GLT-1 subtype of glutamate transporter in glutamate homeostasis: the GLT-1-preferring inhibitor WAY-855 produces marginal neurotoxicity in the rat hippocampus.

Glutamate is the major excitatory neurotransmitter in the central nervous system and is tightly regulated by cell surface transporters to avoid increases in concentration and associated neurotoxicity. Selective blockers of glutamate transporter subtypes are sparse and so knock-out animals and antisense techniques have been used to study their specific roles. Here we used WAY-855, a GLT-1-preferring blocker, to assess the role of GLT-1 in rat hippocampus.

Developmental roles of pufferfish Hox clusters and genome evolution in ray-fin fish.

The pufferfish skeleton lacks ribs and pelvic fins, and has fused bones in the cranium and jaw. It has been hypothesized that this secondarily simplified pufferfish morphology is due to reduced complexity of the pufferfish Hox complexes. To test this hypothesis, we determined the genomic structure of Hox clusters in the Southern pufferfish Spheroides nephelus and interrogated genomic databases for the Japanese pufferfish Takifugu rubripes (fugu).