Stem Cell Based Tissue Engineering and Regenerative Medicine: A Review Focusing on Adult Stem Cells

Tissue engineering has emerged as a field that attempts to harness the bodies\u27 own developmental and repair features to treat diseases and illnesses. Many of these illnesses are caused by necrosis or loss of functionality of complete organs or specific cell types. Early discoveries in embryonic stem cells fueled a wave of research that led to claims about possibly regenerating nonfunctioning organs. Although we are still far away from being able to grow functional organs in a Petri dish, the field continues to progress forward, and new clinical trials have been approved for using both embryonic and adult stem cell based solutions for regenerative medicine and tissue engineering. Current trends have moved towards adult stem cells for cell based therapies as they offer an autologous source and are less tumorigenic than their embryonic and induced-pluripotent stem cell counter parts. This review will begin with an outline of stem cell classes and then focus on current therapies in myocardial tissue repair, neural tissue repair, diabetes, as well as osteogenic and chondrogenic differentiation are also reviewed

Progress of Mesenchymal Stem Cell Therapy for Neural and Retinal Diseases

Complex circuitry and limited regenerative power make central nervous system (CNS) disorders the most challenging and difficult for functional repair. With elusive disease mechanisms, traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases. However, the number of neurons still diminishes in many patients. Recently, stem cell therapy has been proposed as a viable option. Mesenchymal stem cells (MSCs), a widely-studied human adult stem cell population, have been discovered for more than 20 years. MSCs have been found all over the body and can be conveniently obtained from different accessible tissues: bone marrow, blood, and adipose and dental tissue. MSCs have high proliferative and differentiation abilities, providing an inexhaustible source of neurons and glia for cell replacement therapy. Moreover, MSCs also show neuroprotective effects without any genetic modification or reprogramming. In addition, the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation. These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders. Here, we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases. This review article will focus on multiple sclerosis, spinal cord injury, autism, glaucoma, retinitis pigmentosa and age-related macular degeneration

Pluripotent Adult Stem Cells: A Potential Revolution in Regenerative Medicine and Tissue Engineering

Stem cells have generated a lot of excitement among the researchers, clinicians and the public alike. Various types of stem cells are being evaluated for their regenerative potential. Marginal benefit resulting by transplanting autologus stem cells (deemed to be absolutely safe) in various clinical conditions has been proposed to be a growth factor effect rather than true regeneration. In contrast, various pre-clinical studies have been undertaken, using differentiated cells from embryonic stem cells or induced pluripotent stem cells have shown promise, functional improvement and no signs of teratoma formation. The scientists are not in a rush to reach the clinic but a handful of clinical studies have shown promise. This book is a collection of studies/reviews, beginning with an introduction to the pluripotent stem cells and covering various aspects like derivation, differentiation, ethics, etc., and hence would provide insight into the recent standing on the pluripotent stem cells biology. The chapters have been categorized into three sections, covering subjects ranging from the generation of pluripotent stem cells and various means of their derivation from embryonic as well as adult tissues, the mechanistic understanding of pluripotency and narrating the potential therapeutic implications of these in vitro generated cells in various diseases, in addition to the associated pros and cons in the same.https://nsuworks.nova.edu/cnso_bio_facbooks/1014/thumbnail.jp

Ion Mobility and Gas-Phase Covalent Labeling Study of the Structure and Reactivity of Gaseous Ubiquitin Ions Electrosprayed from Aqueous and Denaturing Solutions

Gas-phase ion/ion chemistry was coupled to ion mobility/mass spectrometry analysis to correlate the structure of gaseous ubiquitin to its solution structures with selective covalent structural probes. Collision cross section (CCS) distributions were measured to ensure the ubiquitin ions were not unfolded when they were introduced to the gas phase. Aqueous solutions stabilizing the native state of ubiquitin yielded folded ubiquitin structures with CCS values consistent with previously published literature. Denaturing solutions favored several families of unfolded conformations for most of the charge states evaluated. Gas-phase covalent labeling via ion/ion reactions was followed by collision-induced dissociation of the intact, labeled protein to determine which residues were labeled. Ubiquitin 5+ and 6+ electrosprayed from aqueous conditions were covalently modified preferentially at the lysine 29 and arginine 54 positions, indicating that elements of three-dimensional structure were maintained in the gas phase. On the other hand, most ubiquitin ions produced in denaturing conditions were labeled at various other lysine residues, likely due to the availability of additional sites following methanol- and low-pH-induced unfolding. These data support the conservation of ubiquitin structural elements in the gas phase. The research presented here provides the basis for residue-specific characterization of biomolecules in the gas phase

Gas-Phase Ion/Ion Chemistry for Structurally Sensitive Probes of Gaseous Protein Ion Structure: Electrostatic and Electrostatic to Covalent Cross-Linking

Intramolecular interactions within a protein are key in maintaining protein tertiary structure and understanding how proteins function. Ion mobility-mass spectrometry (IM-MS) has become a widely used approach in structural biology since it provides rapid measurements of collision cross sections (CCS), which inform on the gas-phase conformation of the biomolecule under study. Gas-phase ion/ion reactions target amino acid residues with specific chemical properties and the modified sites can be identified by MS. In this study, electrostatically reactive, gas-phase ion/ion chemistry and IM-MS are combined to characterize the structural changes between ubiquitin electrosprayed from aqueous and denaturing conditions. The electrostatic attachment of sulfo-NHS acetate to ubiquitin via ion/ion reactions and fragmentation by electron-capture dissociation (ECD) provide the identification of the most accessible protonated sites within ubiquitin as the sulfonate group forms an electrostatic complex with accessible protonated side chains. The protonated sites identified by ECD from the different solution conditions are distinct and, in some cases, reflect the disruption of interactions such as salt bridges that maintain the native protein structure. This agrees with previously published literature demonstrating that a high methanol concentration at low pH causes the structure of ubiquitin to change from a native (N) state to a more elongated A state. Results using gas-phase, electrostatic cross-linking reagents also point to similar structural changes and further confirm the role of methanol and acid in favoring a more unfolded conformation. Since cross-linking reagents have a distance constraint for the two reactive sites, the data is valuable in guiding computational structures generated by molecular dynamics. The research presented here describes a promising strategy that can detect subtle changes in the local environment of targeted amino acid residues to inform on changes in the overall protein structure

Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.

Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration

Mass-Matching in Higgsless

Modern extra-dimensional Higgsless scenarios rely on a mass-matching between fermionic and bosonic KK resonances to evade constraints from precision electroweak measurements. After analyzing all of the Tevatron and LEP bounds on these so-called Cured Higgsless scenarios, we study their LHC signatures and explore how to identify the mass-matching mechanism, the key to their viability. We find singly and pair produced fermionic resonances show up as clean signals with 2 or 4 leptons and 2 hard jets, while neutral and charged bosonic resonances are visible in the dilepton and leptonic WZ channels, respectively. A measurement of the resonance masses from these channels shows the matching necessary to achieve $S\simeq 0$. Moreover, a large single production of KK-fermion resonances is a clear indication of compositeness of SM quarks. Discovery reach is below 10 fb$^{-1}$ of luminosity for resonances in the 700 GeV range.Comment: 28 pages, 18 figure

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or