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Stem cell memory

Raul Vizcardo, Nicholas D Klemen, S M Rafiqul Islam, Devikala Gurusamy, Naritaka Tamaoki, Daisuke Yamada, Haruhiko Koseki, Benjamin L Kidder, Zhiya Yu, Li Jia, Amanda N Henning, Meghan L Good, Marta Bosch-Marce, Takuya Maeda, Chengyu Liu, Zied Abdullaev, Svetlana Pack, Douglas C Palmer, David F Stroncek, Fumito Ito, Francis A Flomerfelt, Michael J Kruhlak, Nicholas P Restifo
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+ CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs)...
March 20, 2018: Cell Reports
Hirofumi Noguchi, Chika Miyagi-Shiohira, Yoshiki Nakashima
Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. The pattern of expressed genes, DNA methylation, and covalent histone modifications in iPS cells are very similar to those in ES cells. However, it has recently been shown that, following the reprogramming of mouse/human iPS cells, epigenetic memory is inherited from the parental cells. These findings suggest that the phenotype of iPS cells may be influenced by their cells of origin and that their skewed differentiation potential may prove useful in the generation of differentiated cell types that are currently difficult to produce from ES/iPS cells for the treatment of human diseases...
March 21, 2018: International Journal of Molecular Sciences
Andrea M Byrne, Tal Schechter, Robyn Westmacott
We report the neuropsychological profile of a 6-year-old girl with Wiskott-Aldrich syndrome, a rare X-linked immunodeficiency disorder associated with thrombocytopenia, eczema, recurrent infections, and malignancy. Wiskott-Aldrich syndrome occurs almost exclusively in males and is extremely rare in females, with no known research focused on cognitive and academic functioning in this population. Our patient was referred due to concerns about her memory and academic functioning. She had a history of progressive thrombocytopenia and hematopoietic stem cell transplantation at age 15 months...
March 2018: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
Yin-Qiu Fan, Jing-Cheng Cui, Jun Yang, Pin Wang
OBJECTIVE: To observe the effect of "Huayu Tongluo"(Blood-stasis Dispersing and Meridian-collateral Dredging) moxibustion on the delayed memory and expression of Nestin and Doublecortin (DCX) proteins in the hippocampus in vascular dementia (VD) rats in the view of neurogenesis produced by intracerebral transplantation of neural stem cells (NSCs) and endothelial progenitor cells (EPCs). METHODS: Healthy male Wistar rats were randomized into control group, VD model group,NSCs+EPCs group and NSCs+EPCs moxibustion group...
March 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Nicolle H R Litjens, Lotte van der Wagen, Jurgen Kuball, Jaap Kwekkeboom
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse...
2018: Frontiers in Immunology
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Alexandra J Harvey, Carmel O'Brien, Jack Lambshead, John R Sheedy, Joy Rathjen, Andrew L Laslett, David K Gardner
Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming...
2018: PloS One
Laura B Ngwenya, Sarmistha Mazumder, Zachary R Porter, Amy Minnema, Duane J Oswald, H Francis Farhadi
Cognitive deficits after traumatic brain injury (TBI) are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis...
2018: Stem Cells International
M Radek, J-G Tenberge, S Hilke, G Wilde, M Peterlechner
Electron microscopy images are interference patterns and can generally not be interpreted in a straight forward manner. Typically, time consuming numerical simulations have to be employed to separate specimen features from imaging artifacts. Directly comparing numerical predictions to experimental results, realistic simulation box sizes and varying imaging parameters are needed. In this work, we introduce an accelerated multislice algorithm, named STEMcl, that is capable of simulating series of large super cells typical for defective and amorphous systems, in addition to parameter series using the massive parallelization accessible in today's commercial PC-hardware, e...
February 16, 2018: Ultramicroscopy
Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, Toshiyuki Takai
Plasma cells (PCs) acquiring with long lives in bone marrow (BM) play a pivotal role in the humoral arm of immunological memory. The PCs reside in a special BM niche and produce antibodies against past-encountered pathogens or vaccine components for a long time. In BM, cysteine-X-cysteine (CXC) chemokine receptor type 4-expressing PCs and myeloid cells such as dendritic cells are attracted to and held by CXC chemokine ligand 12-secreting stromal cells, where survival of the PCs is supported by soluble factors such as IL-6 and a proliferation-inducing ligand or APRIL produced by neighboring myeloid cells...
February 24, 2018: International Immunology
Lu Wang, Daniel Hiler, Beisi Xu, Issam AlDiri, Xiang Chen, Xin Zhou, Lyra Griffiths, Marc Valentine, Abbas Shirinifard, András Sablauer, Suresh Thiagarajan, Marie-Elizabeth Barabas, Jiakun Zhang, Dianna Johnson, Sharon Frase, Michael A Dyer
Diverse cell types can be reprogrammed into pluripotent stem cells by ectopic expression of Oct4 (Pou5f1), Klf4, Sox3, and Myc. Many of these induced pluripotent stem cells (iPSCs) retain memory, in terms of DNA methylation and histone modifications (epigenetic memory), of their cellular origins, and this may bias subsequent differentiation. Neurons are difficult to reprogram, and there has not been a systematic side-by-side characterization of reprogramming efficiency or epigenetic memory across different neuronal subtypes...
March 6, 2018: Cell Reports
Jacqueline M Roberts, Monica L Vetter
The use of retinal organoids requires efficient differentiation from induced pluripotent stem cells (iPSCs). In this issue of Cell Reports, Wang et al. (2018) examine how the chromatin landscape after iPSC programming predicts their ability to differentiate into retinal tissue.
March 6, 2018: Cell Reports
Debora Vignali, Elisa Cantarelli, Carlotta Bordignon, Adriana Canu, Antonio Citro, Andrea Annoni, Lorenzo Piemonti, Paolo Monti
Stem memory T cells (Tscm) constitute the earliest developmental stage of memory T cells, displaying stem cell-like properties such as self-renewal capacity. Their superior immune reconstitution potential has sparked interest in cancer immune-therapy, vaccine development and immune reconstitution, whereas their role in autoimmunity is largely unexplored. Here we show that autoreactive CD8+ Tscm specific for β cell antigens GAD65, insulin and IGRP are present in patients with type 1 diabetes (T1D). In vitro, generation of autoreactive Tscm from naïve precursors required the presence of the homeostatic cytokine interleukin-7 (IL-7)...
March 5, 2018: Diabetes
Chinedu Cletus Ude, Azizi Miskon, Ruszymah Bt Hj Idrus, Muhamad Bin Abu Bakar
The dynamic nature of modern warfare, including threats and injuries faced by soldiers, necessitates the development of countermeasures that address a wide variety of injuries. Tissue engineering has emerged as a field with the potential to provide contemporary solutions. In this review, discussions focus on the applications of stem cells in tissue engineering to address health risks frequently faced by combatants at war. Human development depends intimately on stem cells, the mysterious precursor to every kind of cell in the body that, with proper instruction, can grow and differentiate into any new tissue or organ...
February 26, 2018: Military Medical Research
Yan Xu, Satoshi Ikeda, Kentaro Sumida, Ryusuke Yamamoto, Hiroki Tanaka, Nagahiro Minato
Chronic myelogenous leukemia (CML) caused by hematopoietic stem cells expressing the Bcr-Abl fusion gene may be controlled by Bcr-Abl tyrosine kinase inhibitors (TKIs). However, CML-initiating cells are resistant to TKIs and may persist as minimal residual disease. We demonstrate that mice deficient in Sipa1, which encodes Rap1 GTPase-activating protein, rarely develop CML upon transfer of primary hematopoietic progenitor cells (HPCs) expressing Bcr-Abl, which cause lethal CML disease in wild-type mice. Resistance requires both T cells and nonhematopoietic cells...
March 2, 2018: Nature Communications
Nina Müller, Katharina Landwehr, Kirsten Langeveld, Joanna Stenzel, Walter Pouwels, Menno A W G van der Hoorn, Erhard Seifried, Halvard Bonig
BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+ ) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution...
February 28, 2018: Cytotherapy
Deniz Genç, Noushin Zibandeh, Ercan Nain, Muazzez Gökalp, Ahmet Oğuzhan Özen, Mehmet Kamil Göker, Tunç Akkoç
BACKGROUND: Asthma is a chronic inflammatory disease in which inflammatory responses have the polarization of CD4+ T cells to Th2 cells. Dental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells. OBJECTIVE: We investigated the immunomodulatory effects of DFSCs on CD4+ T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals...
March 2, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Fabian Schlott, Dominik Steubl, Stefanie Ameres, Andreas Moosmann, Stefan Dreher, Uwe Heemann, Volker Hösel, Dirk H Busch, Michael Neuenhahn
Human Cytomegalovirus (CMV) reactivation remains a major source of morbidity in patients after solid organ and hematopoietic stem cell transplantation (HSCT). Adoptive T cell therapy (ACT) with CMV-specific T cells is a promising therapeutic approach for HSCT recipients, but might be counteracted by CMV's immune evasion strategies. HLA-C*07:02 is less susceptible to viral immune evasion suggesting HLA-C*07:02-restricted viral epitopes as promising targets for ACT. For a better understanding of HLA-C*07:02-restricted CMV-specific T cells we used recently generated reversible HLA-C*07:02/IE-1 multimers (Streptamers) recognizing a CMV-derived Immediate-Early-1 (IE-1) epitope and analyzed phenotypic and functional T cell characteristics...
2018: PloS One
Coco de Koning, Rick Admiraal, Stefan Nierkens, Jaap Jan Boelens
Human herpesvirus 6 (HHV6) viremia is a common cause of morbidity following allogeneic hematopoietic cell transplantation (HCT). We previously associated T-cell reconstitution with HHV6 viremia. Here, we investigated whether HHV6 viremia affects T-cell reconstitution after HCT in a time-dependent retrospective analysis. We included 273 pediatric patients (0.1-22.7 years; median follow-up, 58 months) receiving a first HCT between 2004 and 2014. HHV6 was screened weekly in plasma via polymerase chain reaction and occurred in 79 patients (29%) at a median time of 19 days after transplant...
February 27, 2018: Blood Advances
Yan Li, Yanhui Li, Weihong Ji, Zhiguo Lu, Linying Liu, Yuanjie Shi, Guanghui Ma, Xin Zhang
Due to the vast differences in chemical properties among small molecule drugs, nucleotide drugs and superparamagnetic iron oxide nanocubes (SPIONs), such as charge and hydrophobicity, entrapment of these within a single carrier for traceable synergistic therapy has been proven difficult. Herein, we synthesize positively charged polyprodrug amphiphiles. The hydrophobic polyprodrug unit of the amphiphiles is positively charged, which can simultaneously load hydrophobic SPIONs and absorb negative let-7b antisense oligonucleotide to construct traceable co-delivery nanoparticles (NPs)...
February 27, 2018: Journal of the American Chemical Society
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