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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

3D cell culture --- biomaterial disease models --- Neuron --- neurodegeneration --- tumor --- Blood Brain Barrier (BBB) --- Brain Disorders --- Hydrogels --- iPSC = induced pluripotent stem cell --- Bioprinting

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Following the implementation of next-generation sequencing technologies (e.g., exome and genome sequencing) in molecular diagnostics, the majority of genetic defects underlying inherited retinal disease (IRD) can readily be identified. In parallel, opportunities to counteract the molecular consequences of these defects are rapidly emerging, providing hope for personalized medicine. ‘Classical’ gene augmentation therapy has been under study for several genetic subtypes of IRD and can be considered a safe and sometimes effective therapeutic strategy. The recent market approval of the first retinal gene augmentation therapy product (LuxturnaTM, for individuals with bi-allelic RPE65 mutations) by the FDA has not only demonstrated the potential of this specific approach, but also opened avenues for the development of other strategies. However, every gene—or even every mutation—may need a tailor-made therapeutic approach, in order to obtain the most efficacious strategy with minimal risks associated. In addition to gene augmentation therapy, other subtypes of molecular therapy are currently being designed and/or implemented, including splice modulation, DNA or RNA editing, optogenetics and pharmacological modulation. In addition, the development of proper delivery vectors has gained strong attention, and should not be overlooked when designing and testing a novel therapeutic approach. In this Special Issue, we aim to describe the current state of the art of molecular therapeutics for IRD, and discuss existing and novel therapeutic strategies, from idea to implementation, and from bench to bedside.

induced pluripotent stem cell (iPSC) --- clustered regularly interspaced short palindromic repeats (CRISPR) --- homology-directed repair (HDR) --- Enhanced S-Cone Syndrome (ESCS) --- NR2E3 --- AAV --- retina --- gene therapy --- dual AAV --- gold nanoparticles --- DNA-wrapped gold nanoparticles --- ARPE-19 cells --- retinal pigment epithelium --- clathrin-coated vesicles --- endosomal trafficking --- retinitis pigmentosa --- autosomal dominant --- G56R --- putative dominant negative effect --- gapmer antisense oligonucleotides --- allele-specific knockdown --- Leber congenital amaurosis and allied retinal ciliopathies --- CEP290 --- Flanders founder c.4723A &gt --- T nonsense mutation --- Cilia elongation --- spontaneous nonsense correction --- AON-mediated exon skipping --- microRNA --- photoreceptors --- rods --- cones --- bipolar cells --- Müller glia --- retinal inherited disorders --- retinal degeneration --- antisense oligonucleotides --- Stargardt disease --- inherited retinal diseases --- splicing modulation --- RNA therapy --- ABCA4 --- iPSC-derived photoreceptor precursor cells --- cyclic GMP --- apoptosis --- necrosis --- drug delivery systems --- translational medicine --- Usher syndrome --- Leber congenital amaurosis --- RPE65 --- nonprofit --- patient registry --- translational --- protein trafficking --- protein folding --- protein degradation --- chaperones --- chaperonins --- heat shock response --- unfolded protein response --- autophagy --- therapy --- IRD --- DNA therapies --- RNA therapies --- compound therapies --- clinical trials --- Retinitis Pigmentosa GTPase Regulator --- adeno-associated viral --- Retinitis Pigmentosa (RP) --- choroideremia --- REP1 --- inherited retinal disease --- treatment --- apical polarity --- crumbs complex --- fetal retina --- PAR complex --- retinal organoids --- retinogenesis --- gene augmentation --- adeno-associated virus (AAV) --- n/a --- Müller glia

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Recently, stem cells have been drawing increasing interest in basic and translational research that aims to understand stem cell biology and generate new therapies for various disorders. Many stem cells can be cultured in 2D relatively easily using tissue culture plastic. However, many of these cultures do not represent the natural conditions of stem cells in the body. In the body, microenvironments include numerous supporting cells and molecules. Therefore, researchers and clinicians have sought ideal stem cell preparations for basic research and clinical applications, which may be attainable through 3D culture of stem cells. The 3D cultures mimic the conditions of the natural environment of stem cells better, as cells in 3D cultures exhibit many unique and desirable characteristics that could be beneficial for therapeutic interventions. 3D stem cell cultures may employ supporting structures, such as various matrices or scaffolds, in addition to stem cells, to support complex structures. This book brings together recent research on 3D cultures of various stem cells to increase the basic understanding of stem cell culture techniques and also to highlight stem cell preparations for possible novel therapeutic applications.

hematopoiesis --- hematopoietic stem cells --- stem cell culture --- 2D culture --- 3D culture --- embryonic stem cells --- three-dimensional --- self-assembling scaffold --- pluripotency --- culture conditions --- expansion --- growth --- niche --- human cortical progenitors --- silicon pillars --- cell growth --- hiPSC-derived neural progenitors --- cerebral cortex --- carcinogen --- protein phosphatase 2A (PP2A) --- intestinal tumor --- intestinal organoid --- Lgr5+ crypt stem cell --- mouse embryonic stem cell --- differentiation protocol --- ureteric bud progenitor cells --- 3D kidney organoids --- intestinal organoids --- canine intestine --- differentiation --- organoid culture --- induced pluripotent stem cells --- neurospheres --- neurite outgrowth --- neurotoxicity --- hBM-MSCs --- cytokines --- tenogenic markers --- cyclic strain --- 3D microenvironment --- PLGA carriers --- bioreactor --- cardiac microtissues --- iPSC-derived cardiomyocytes --- cardiac fibroblasts --- cardiac fibrosis --- cardiac rhythm --- TGF-β signalling --- drug screening --- in vitro model --- stem cell --- 3D --- culture condition --- regenerative medicine --- scaffold --- organoid --- adipose tissue-derived mesenchymal stem cells --- stromal vascular fraction --- platelet rich plasma --- platelet concentrates --- veterinary regenerative medicine

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Vision is the most important sense in higher mammals. The retina is the first step in visual processing and the window to the brain. It is not surprising that problems arising in the retina lead to moderate to severe visual impairments. We offer here a collection of reviews as well as original papers dealing with various aspects of retinal function as well as dysfunction. New approaches in retinal research are described, such as the expression and localization of the endocannabinoid system in the normal retina and the role of cannabinoid receptors that could offer new avenues of research in the development of potential treatments for retinal diseases. Moreover, new insights are offered in advancing knowledge towards the prevention and cure of visual pathologies, mainly AMD, RP, and diabetic retinopathy.

eye --- retina --- development --- vascularization --- hypoxia --- autophagy --- programmed cell death --- cellular senescence --- retinogenesis --- altricial bird species --- precocial bird species --- senescence-associated galactosidase activity --- diabetes mellitus --- retinopathy --- microvascular --- complication --- optical coherence tomography --- angiography --- black --- African-American --- systemic disease --- biomarker --- retinal degenerative diseases --- mesenchymal stem cells --- stem cell therapy --- experimental models --- clinical trials --- AMD --- age-related macular degeneration --- trichostatin A (TSA) --- HDAC --- histone deacetylase --- vascular endothelial growth factor (VEGF) --- retinal degeneration --- endoplasmic reticulum --- stress response --- unfolded protein response --- GRP78 --- retinal glial cell --- diabetic retinopathy --- zebrafish --- neurovascular unit --- microvascular complications and dysfunction --- metabolism --- motor protein --- myosin 1C --- photoreceptor --- rhodopsin --- outer segments --- visual function --- macroglia --- astrocytes --- Müller cells --- optic nerve crush --- retinal ganglion cells --- spinal cord injury --- signal transducer and activator of transcription 3 --- epidermal growth factor --- Drp1 --- apoptosis --- mitochondria --- microglia --- neurodegeneration --- multiple sclerosis --- retinal microglia --- microglia morphotype --- light damage --- functional analysis --- early detection --- remodeling --- lactate --- GPR81 --- HCAR1 --- growth cone --- dLGN --- axon --- 3,5-DHBA --- kallikrein-kinin system --- kinin receptors --- GFAP --- osteopontin --- retinal detachment --- diabetes --- antioxidants --- bioenergetics --- respiration --- ATP --- glucagon-like peptide-1 --- exendin-4 --- catalase --- immunohistochemistry --- electron microscopy --- Charles Bonnet syndrome --- EEG --- visual hallucination --- resting state --- high-fat diet --- gut microbiome --- gut-retina axis --- RNA sequencing --- germ-free mice --- complement cascade --- angiogenesis --- retinal inflammation --- AII amacrine cell --- Prox1 --- parvalbumin --- gap junction --- eccentricity --- ON/OFF asymmetry --- arterioles --- betulinic acid --- ischemia-reperfusion injury --- reactive oxygen species --- retinal vessels --- retinal fluorescence imaging --- amyloid --- cognitive decline --- Alzheimer’s disease --- optic neuritis --- oxidative stress --- neuroprotection --- fingolimod --- iPSC-RPE --- retinal pigment epithelium --- immunodeficient RCS rat --- ultrathin parylene --- retinal transplantation --- CD4+CD25+ --- inflammation --- iPSC --- typical cannabinoid receptors --- atypical cannabinoid receptors --- electroretinography --- monkeys --- visual system --- eye inflammation --- lipopolysaccharide --- natural bioactive extracts --- Ac2-26 --- FPR receptor --- inflammatory mediators --- retinal light injury --- LED screen --- optical filter --- retinal protection --- regeneration --- progenitor cell --- hyperglycemia --- photoreceptors --- neurod --- Notch --- n/a --- Müller cells --- Alzheimer's disease

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Even today, cardiovascular diseases are the main cause of death worldwide, and therapeutic approaches are very restricted. Due to the limited regenerative capabilities of terminally differentiated cardiomyocytes post injury, new strategies to treat cardiac patients are urgently needed. Post myocardial injury, resident fibroblasts begin to generate the extracellular matrix, resulting in fibrosis, and finally, cardiac failure. Recently, preclinical investigations and clinical trials raised hope in stem cell-based approaches, to be an effective therapy option for these diseases. So far, several types of stem cells have been identified to be promising candidates to be applied for treatment: cardiac progenitor cells, bone marrow derived stem cells, embryonic and induced pluripotent stem cells, as well as their descendants. Furthermore, the innovative techniques of direct cardiac reprogramming of cells offered promising options for cardiovascular research, in vitro and in vivo. Hereby, the investigation of underlying and associated mechanisms triggering the therapeutic effects of stem cell application is of particular importance to improve approaches for heart patients. This Special Issue of Cells provides the latest update in the rapidly developing field of regenerative medicine in cardiology.

Fabry disease --- human embryonic stem cells --- CRISPR/Cas9 genomic editing --- Mass spectrometry proteomic analysis --- hypertrophic cardiomyopathy --- disease model --- physical exercise --- cardiac cellular regeneration --- microRNA (miR) --- Akt signaling --- cardiomyocyte proliferation --- cardiac hypertrophy --- cardioprotection --- myocarditis --- inflammation --- leukocytes --- cardiomyocytes --- multi-electrode-array --- micro-electrode-array --- MEA --- drug/toxicity screening --- field potential --- arrhythmia --- electrocardiography --- cardiac regeneration --- stem cells --- iPSC --- PSC --- ESC --- cardiovascular disease --- regeneration --- cardiac progenitor cells --- induced pluripotent stem cells --- transdifferentiation --- direct reprogramming --- genetic engineering --- cardiac tissue engineering --- biomaterials --- 18F-FDG PET --- cardiac induced cells --- cardiac function --- non-invasive imaging --- human pluripotent stem cell --- ventricular --- maturation --- bone marrow stem cells --- angiogenesis --- myocardial infarction --- human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) --- iPS cells --- big conductance calcium activated potassium channel (BK) --- Maxi-K --- slo1 --- KCa1.1 --- iberiotoxin --- long QT syndrome --- mesenchymal stromal cells (MSC) --- mRNA --- miRNA --- cardiac reprogramming --- cardiac differentiation --- cardiovascular diseases --- adult stem cells --- myocardial infraction --- 3D printing --- 3D model --- bioprinting --- cardiovascular medicine --- heart --- myocardium --- heart valves --- vascular graft --- endothelialization --- tissue engineering --- decorin --- fibronectin --- electrospinning --- endothelial progenitor cells --- bioreactor --- biostable polyurethane --- MicroRNA --- Mir-133 --- coronary heart disease --- biomarker --- meta-analysis