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This Research Topic honors the memory of Prof. Antonius “Ton” G. Rolink (April 19, 1953–August 06, 2017), our colleague, mentor and friend in immunology. It is now over a year since Ton left us. This article collection, authored by many of Ton’s friends and colleagues, reflects the huge contribution to cellular and molecular immunology that work emanating directly from Ton’s own hands and laboratory have made to the understanding of lymphocyte development. Ton’s hard work, expertise, generosity, passion for science and infectious humor were legendary and for all of those lucky enough to have been his colleague, he ensured that science was fun. We take this opportunity of thanking all contributors for submitting their manuscripts; we are sure that Ton would have enjoyed reading and making his own insightful comments on them. In the form of original research and review articles, these papers cover many of Ton’s scientific interests in different aspects of lymphocyte development in mouse and man. In the first section, Development of hematopoietic cells and lymphocytes, Klein et al. describe the accumulation of multipotent hematopoietic progenitors in peripheral lymphoid organs of IL-7xFlt3L double transgenic mice and Pang et al. the role of the transcription factor PU.1 on the development of Common Lymphoid Progenitors. In Early B cell development, Winkler and Mårtensson review the role of the Pre-B cell receptor in B cell development and papers by Hobeika et al. and Brennecke et al. describe models of inducible B cell development. For B cell selection, survival and tolerance, Smulski and Eibel review the role of BAFF and Kowalczyk-Quintans et al. analyse the role of membrane-bound BAFF. The impact of BIM on B cell homeostasis is discussed by Liu et al. The role of the MEK-ERK pathway in B cell tolerance is discussed by Greaves et al. and the transcriptional regulation of germinal center development is reviewed by Song and Matthias. For Hematological diseases, Ghia reviews how studies of B cell development help the understanding of Leukemia development, Kim and Schaniel review how iPS technology helps the understanding of hematological diseases and Hellmann et al. describe development of new therapeutic antibody drug conjugates. Finally, in T cell development, homeostasis and graft vs. host disease, Heiler et al. describe the therapeutic effects of IL-2/anti-IL-2 immune complexes in GvHD, Calvo-Asensio et al. describe the DNA damage response of thymocyte progenitors and Mori and Pieters review the role of Coronin 1 in T cell survival.

T cell development --- B cell selection and survival --- BAFF --- Cytokines --- IPSC --- Leukemia --- T cell survival --- Transcription Factors --- B cell development --- Hematopoietic Stem Cells

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This Research Topic honors the memory of Prof. Antonius “Ton” G. Rolink (April 19, 1953–August 06, 2017), our colleague, mentor and friend in immunology. It is now over a year since Ton left us. This article collection, authored by many of Ton’s friends and colleagues, reflects the huge contribution to cellular and molecular immunology that work emanating directly from Ton’s own hands and laboratory have made to the understanding of lymphocyte development. Ton’s hard work, expertise, generosity, passion for science and infectious humor were legendary and for all of those lucky enough to have been his colleague, he ensured that science was fun. We take this opportunity of thanking all contributors for submitting their manuscripts; we are sure that Ton would have enjoyed reading and making his own insightful comments on them. In the form of original research and review articles, these papers cover many of Ton’s scientific interests in different aspects of lymphocyte development in mouse and man. In the first section, Development of hematopoietic cells and lymphocytes, Klein et al. describe the accumulation of multipotent hematopoietic progenitors in peripheral lymphoid organs of IL-7xFlt3L double transgenic mice and Pang et al. the role of the transcription factor PU.1 on the development of Common Lymphoid Progenitors. In Early B cell development, Winkler and Mårtensson review the role of the Pre-B cell receptor in B cell development and papers by Hobeika et al. and Brennecke et al. describe models of inducible B cell development. For B cell selection, survival and tolerance, Smulski and Eibel review the role of BAFF and Kowalczyk-Quintans et al. analyse the role of membrane-bound BAFF. The impact of BIM on B cell homeostasis is discussed by Liu et al. The role of the MEK-ERK pathway in B cell tolerance is discussed by Greaves et al. and the transcriptional regulation of germinal center development is reviewed by Song and Matthias. For Hematological diseases, Ghia reviews how studies of B cell development help the understanding of Leukemia development, Kim and Schaniel review how iPS technology helps the understanding of hematological diseases and Hellmann et al. describe development of new therapeutic antibody drug conjugates. Finally, in T cell development, homeostasis and graft vs. host disease, Heiler et al. describe the therapeutic effects of IL-2/anti-IL-2 immune complexes in GvHD, Calvo-Asensio et al. describe the DNA damage response of thymocyte progenitors and Mori and Pieters review the role of Coronin 1 in T cell survival.

T cell development --- B cell selection and survival --- BAFF --- Cytokines --- IPSC --- Leukemia --- T cell survival --- Transcription Factors --- B cell development --- Hematopoietic Stem Cells --- T cell development --- B cell selection and survival --- BAFF --- Cytokines --- IPSC --- Leukemia --- T cell survival --- Transcription Factors --- B cell development --- Hematopoietic Stem Cells

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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

Civil engineering, surveying & building --- Mechanical engineering & materials --- 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.

Research & information: general --- Biology, life sciences --- 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) --- 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)

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The regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) have made these cells the focus of multiple pre-clinical studies and clinical trials. While the results from these clinical studies have established that MSCs are safe, the efficacy of these cells is not as well-established. In this regard, there have been increased efforts towards generating potentiated/activated MSCs with enhanced therapeutic efficacy. Research on the mechanisms for enhancing MSC potency and efficacy is an area of active study with great potential for translation into clinical settings. The purpose of this book is to bring together recent research from a broad range of topics relating to potentiation strategies for enhancing MSC therapeutic efficacy, including growth factor pre-conditioning, hypoxia, and 3D culture. The research compiled in this book increases the basic understanding of MSC culture techniques and describes some MSC preparations for potential novel therapeutic applications.

Medicine --- cell therapy --- immunomodulation --- polyunsaturated fatty acid --- CD206 --- phagocytosis --- mesenchymal stem cells --- Vadadustat --- AKB-6548 --- preconditioning --- priming --- secretome --- chemotaxis --- Wharton’s jelly mesenchymal stem cells --- umbilical cord --- oxygen conditions --- secretory profile --- neuroprotection --- mesenchymal stromal cells --- 3D culture --- neurospheres --- spheroids --- pluripotency --- neural --- quiescence --- mesothelioma --- malignant pleural mesothelioma (MPM) --- liver cirrhosis --- placenta-derived mesenchymal stem cells --- WKYMVm --- combination therapy --- iPSC-derived MSCs --- iMSC secretome --- pre-conditioning --- angiogenesis --- IFN-γ --- hypoxia --- potentiation of iMSC efficacy --- nanofiber-hydrogel composite --- spinal cord injury --- inflammation --- macrophages --- secondary injury --- astrocytes --- axon growth --- adipose tissue-derived stem cells (ASCs) --- autophagy --- rapamycin --- 3-methyladenine --- immunosuppression --- exosome --- engineered cardiac patches --- adipose-derived stem cell --- paracrine potential --- osteogenic differentiation --- hepatocyte growth factor --- fibroblast growth factor 2 --- cell therapy --- immunomodulation --- polyunsaturated fatty acid --- CD206 --- phagocytosis --- mesenchymal stem cells --- Vadadustat --- AKB-6548 --- preconditioning --- priming --- secretome --- chemotaxis --- Wharton’s jelly mesenchymal stem cells --- umbilical cord --- oxygen conditions --- secretory profile --- neuroprotection --- mesenchymal stromal cells --- 3D culture --- neurospheres --- spheroids --- pluripotency --- neural --- quiescence --- mesothelioma --- malignant pleural mesothelioma (MPM) --- liver cirrhosis --- placenta-derived mesenchymal stem cells --- WKYMVm --- combination therapy --- iPSC-derived MSCs --- iMSC secretome --- pre-conditioning --- angiogenesis --- IFN-γ --- hypoxia --- potentiation of iMSC efficacy --- nanofiber-hydrogel composite --- spinal cord injury --- inflammation --- macrophages --- secondary injury --- astrocytes --- axon growth --- adipose tissue-derived stem cells (ASCs) --- autophagy --- rapamycin --- 3-methyladenine --- immunosuppression --- exosome --- engineered cardiac patches --- adipose-derived stem cell --- paracrine potential --- osteogenic differentiation --- hepatocyte growth factor --- fibroblast growth factor 2