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https://www.readbyqxmd.com/read/29352225/a-humanized-mouse-model-of-liver-fibrosis-following-expansion-of-transplanted-hepatic-stellate-cells
#1
Daniel Benten, Johannes Kluwe, Jan W Wirth, Nina D Thiele, Antonia Follenzi, Kuldeep K Bhargava, Christopher J Palestro, Michael Koepke, Reni Tjandra, Tassilo Volz, Marc Lutgehetmann, Sanjeev Gupta
Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice...
January 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29352176/renal-scattered-tubular-like-cells-confer-protective-effects-in-the-stenotic-murine-kidney-mediated-by-release-of-extracellular-vesicles
#2
Xiangyu Zou, Soon Hyo Kwon, Kai Jiang, Christopher M Ferguson, Amrutesh S Puranik, Xiangyang Zhu, Lilach O Lerman
To test the hypothesis that intrinsic renal scattered tubular cells (STC-like cells) contribute to repairing injured tubular epithelial cells (TEC) by releasing extracellular vesicle (EV). EV released from primary cultured pig STC-like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury, oxidative stress and mitochondrial function were assessed...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#3
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29351404/type-2-diabetes-impairs-the-ability-of-skeletal-muscle-pericytes-to-augment-postischemic-neovascularization-in-db-db-mice
#4
Katherine L Hayes, Louis M Messina, Lawrence M Schwartz, Jinglian Yan, Amy S Burnside, Sarah Witkowski
Peripheral artery disease is an atherosclerotic occlusive disease that causes limb ischemia and has few effective non-interventional treatments. Stem cell therapy is promising, but concomitant diabetes may limit its effectiveness. We evaluated the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization in wild type and type 2 diabetic (T2DM) mice. Wild type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice underwent unilateral femoral artery excision to induce limb ischemia...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29345390/wnt-%C3%AE-catenin-pathway-promotes-early-engraftment-of-fetal-hematopoietic-stem-progenitor-cells
#5
Edward O Kwarteng, Roxann Hétu-Arbour, Krista M Heinonen
The switch from fetal to adult hematopoietic stem/progenitor cells (HSPCs) is associated with profound changes in several genetic programs. Although HSPC ageing corresponds to alterations in Wnt signaling, relatively little is known about the relative roles of different Wnt signaling pathways in HSPC ontogeny. We hypothesized that proliferating fetal HSPCs would be more dependent on canonical β-catenin-dependent Wnt signaling when compared to quiescent adult bone marrow HSPCs. We have compared here Wnt signaling activities in murine fetal and adult HSPCs and demonstrate a shift from Wnt/β-catenin-dependent signaling in fetal liver HSPCs to more predominantly noncanonical Wnt/polarity signaling in adult HSPCs...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345200/distinct-niches-within-the-extracellular-matrix-dictate-fibroblast-function-in-cell-free-3d-lung-tissue-cultures
#6
Gerald Burgstaller, Arunima Sengupta, Sarah Vierkotten, Gerhard Preissler, Michael Lindner, Jürgen Behr, Melanie Königshoff, Oliver Eickelberg
Instructive cues from the extracellular matrix (ECM) and their functional interplay with cells play pivotal roles for development, tissue repair, and disease. However, the precise nature of this interplay remains elusive. We used an innovative 3D cell culture ECM model by decellularizing ex vivo lung tissue scaffolds (d3D-LTCs) derived from diseased and healthy mouse lungs, which widely mimics the native (patho)physiological in vivo microenvironment. We successfully repopulated all d3D-LTCs with primary human and murine fibroblasts...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29345084/the-lived-experience-of-autologous-stem-cell-transplanted-patients-post-transplantation-and-before-discharge
#7
Qasem Alnasser, Salahel Deen Abu Kharmah, Manal Attia, Akram Aljafari, Felicia Agyekum, Falak Aftab
AIMS: The aim of this study was to explore the lived experience of the patients post hematopoietic stem cell transplantation (HSCT) and specifically after engraftment and before discharge. BACKGROUND: Patients post stem cell transplantation experience significant changes in all life aspects. Previous studies done by other researchers focused mainly on the post discharge experience, where patients reported their perceptions that has always been affected by the life post transplantation and influenced by their surroundings...
January 18, 2018: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/29344995/activation-of-human-cd141-and-cd1c-dendritic-cells-in-vivo-with-combined-tlr-3-and-tlr-7-8-ligation
#8
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29344586/systemic-multilineage-engraftment-in-mice-after-in-utero-transplantation-with-human-hematopoietic-stem-cells
#9
Russell G Witt, Emily M Kreger, Laura B Buckman, Patriss W Moradi, Phong T Ho, S Christopher Derderian, Perry Tsai, Chris Baker, Nathaniel Schramm, Rachel Cleary, J Victor Garcia, Tippi C MacKenzie
IUHCT of human cord blood-derived CD34+ cells into fetal NSG mice results in systemic multilineage engraftment with human cells.Preconditioning with in utero injection of an anti-c-Kit receptor antibody (ACK2) results in an improved rate of engraftment.
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29343582/hiv-replication-and-latency-in-a-humanized-nsg-mouse-model-during-suppressive-oral-combinational-art
#10
Sangeetha Satheesan, Haitang Li, John C Burnett, Mayumi Takahashi, Shasha Li, Shiny Xiaqin Wu, Timothy W Synold, John J Rossi, Jiehua Zhou
Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, they cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343525/lack-of-remuscularization-following-transplantation-of-human-embryonic-stem-cell-derived-cardiovascular-progenitor-cells-in-infarcted-nonhuman-primates
#11
Keyang Zhu, Qiang Wu, Cheng Ni, Peng Zhang, Zhiwei Zhong, Yan Wu, Yingchao Wang, Yinchuan Xu, Minjian Kong, Haifeng Cheng, Zhihua Tao, Qian Yang, He Liang, Yun Jiang, Qingju Li, Jing Zhao, Jijun Huang, Fengjiang Zhang, Qi Chen, Yi Li, Jinghai Chen, Wei Zhu, Hong Yu, Jianyi Zhang, Huang-Tian Yang, Xinyang Hu, Jian'an Wang
Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials. Objective: To clarify if hPSC-CVPCs can engraft for long time in the heart of primates after myo-cardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cy-closporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and Simulect in cynomolgous monkeys that had received intramyocardial injections of 1×107 EGFP-expressing hPSC-CVPCs after MI...
January 17, 2018: Circulation Research
https://www.readbyqxmd.com/read/29342143/regulation-of-embryonic-haematopoietic-multipotency-by-ezh1
#12
Linda T Vo, Melissa A Kinney, Xin Liu, Yuannyu Zhang, Jessica Barragan, Patricia M Sousa, Deepak K Jha, Areum Han, Marcella Cesana, Zhen Shao, Trista E North, Stuart H Orkin, Sergei Doulatov, Jian Xu, George Q Daley
All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29341932/synthetic-extracellular-matrix-mimic-hydrogel-improves-efficacy-of-mesenchymal-stromal-cell-therapy-for-ischemic-cardiomyopathy
#13
Maria Chiara Ciuffreda, Giuseppe Malpasso, Cindy Chokoza, Deon Bezuidenhout, Kyle P Goetsch, Manuela Mura, Federica Pisano, Neil H Davies, Massimiliano Gnecchi
BACKGROUND: Mesenchymal stromal cells (MSC) repair infarcted hearts mainly through paracrine mechanisms. Low cell engraftment limits the release of soluble paracrine factors (SF) over time and, consequently, MSC efficacy. We tested whether a synthetic extracellular matrix mimic, a hydrogel containing heparin (H-HG), could ameliorate MSC engraftment and binding/release of SF, thus improving MSC therapy efficacy. METHODS AND RESULTS: In vitro, rat bone-marrow MSC (rBM-MSC) were seeded and grown into H-HG...
January 13, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29338383/the-process-of-engraftment-of-myogenic-cells-in-skeletal-muscles-of-primates-understanding-clinical-observations-and-setting-directions-in-cell-transplantation-research
#14
Daniel Skuk, Jacques P Tremblay
We studied in macaques the evolution of the intramuscular transplantation of muscle precursor cells between the time of administration and the time at which the graft is considered stable. Satellite cell-derived myoblasts labeled with ß-galactosidase were transplanted into 1 cm3 muscle regions following cell culture and transplantation protocols similar to our last clinical trials. These regions were biopsied 1 h, 1, 3, 7 d, and 3 wk later and analyzed by histology. We observed that the cell suspension leaks from the muscle bundles during injection toward the epimysium and perimysium, where most cells accumulate after transplantation...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338381/effect-of-the-diabetic-state-on-islet-engraftment-and-function-in-a-large-animal-model-of-islet-kidney-transplantation
#15
Prashanth Vallabhajosyula, Atsushi Hirakata, Matthew Weiss, Adam Griesemer, Akira Shimizu, Hanzhou Hong, Andreas Habertheuer, Vaja Tchipashvili, Kazuhiko Yamada, David H Sachs
In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29336814/inhibition-of-interleukin-10-in-the-tumor-microenvironment-can-restore-mesothelin-chimeric-antigen-receptor-t-cell-activity-in-pancreatic-cancer-in-vitro
#16
Ramesh B Batchu, Oksana V Gruzdyn, Ebrahem M Mahmud, Fatme Chukr, Rajesh Dachepalli, Santosh K Manmari, Gamal Mostafa, Donald W Weaver, Scott A Gruber
BACKGROUND: Pancreatic cancer cells are known to shield themselves from immunosurveillance by secreting immune inhibitory cytokines such as Interleukin-10. Using mesothelin, a differentiating antigen that is overexpressed in pancreatic cancer, we assessed the negative effect of the tumor microenvironment on chimeric antigen receptor T cell-based immunotherapy and its reversal via depletion of Interleukin-10. METHODS: T cells cultured in pancreatic cancer-cell-conditioned medium were transduced with lentiviruses encoding mesothelin-chimeric antigen receptor in the presence or absence of anti-Interleukin-10-blocking antibody...
January 11, 2018: Surgery
https://www.readbyqxmd.com/read/29336552/engineering-the-surface-of-therapeutic-living-cells
#17
Jooyeon Park, Brenda Andrade, Yongbeom Seo, Myung-Joo Kim, Steven C Zimmerman, Hyunjoon Kong
Biological cells are complex living machines that have garnered significant attention for their potential to serve as a new generation of therapeutic and delivery agents. Because of their secretion, differentiation, and homing activities, therapeutic cells have tremendous potential to treat or even cure various diseases and injuries that have defied conventional therapeutic strategies. Therapeutic cells can be systemically or locally transplanted. In addition, with their ability to express receptors that bind specific tissue markers, cells are being studied as nano- or microsized drug carriers capable of targeted transport...
January 16, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29335631/impact-of-hla-allele-mismatch-at-hla-a-b-c-drb1-and-dqb1-on-outcomes-in-haploidentical-stem-cell-transplantation
#18
Ming-Rui Huo, Xu-Ying Pei, Dan Li, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
The impact of human leukocyte antigen (HLA) allele mismatch on transplant outcomes in haploidentical stem cell transplantation (haplo-SCT) has not been established. We retrospectively studied 595 patients with hematologic malignancy who received haplo-SCT. The impact of multiple HLA allele mismatches (HLA-A, -B, -C, -DRB1, and -DQB1) and each HLA allele mismatch on transplant outcomes was analyzed. Greater number of HLA allele disparity does not appear worsen outcome. As for each HLA locus, HLA-A mismatch correlated with decreased rate of platelet engraftment (HR 0...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29335625/the-european-society-for-blood-and-marrow-transplantation-ebmt-consensus-guidelines-for-the-detection-and-treatment-of-donor-specific-anti-hla-antibodies-dsa-in-haploidentical-hematopoietic-cell-transplantation
#19
REVIEW
Stefan O Ciurea, Kai Cao, Marcelo Fernadez-Vina, Piyanuch Kongtim, Monzr Al Malki, Ephraim Fuchs, Leo Luznik, Xiao-Jun Huang, Fabio Ciceri, Franco Locatelli, Franco Aversa, Luca Castagna, Andrea Bacigalupo, Massimo Martelli, Didier Blaise, Rupert Handgretinger, Denis-Claude Roy, Paul O'Donnell, Asad Bashey, Hillard M Lazarus, Karen Ballen, Bipin N Savani, Mohamad Mohty, Arnon Nagler
Haploidentical donors are now increasingly considered for transplantation in the absence of HLA-matched donors or when an urgent transplant is needed. Donor-specific anti-HLA antibodies (DSA) have been recently recognized as an important barrier against successful engraftment of donor cells, which can affect transplant survival. DSA appear more prevalent in this type of transplant due to higher likelihood of alloimmunization of multiparous females against offspring's HLA antigens, and the degree of mismatch...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29334850/an-immunopathological-evaluation-of-the-porcine-cholecyst-matrix-as-a-muscle-repair-graft-in-a-male-rat-abdominal-wall-defect-model
#20
Dhanush Krishna Balakrishnan-Nair, Narayanan Divakaran Nair, Syam Kunnekkattu Venugopal, Vijayan Narayana Das, Sisilamma George, Mammen John Abraham, Saji Eassow, Malcolm Ronald Alison, Anoop Sainulabdeen, Thapasimuthu Vijayamma Anilkumar
With the increasing use of animal-based biomaterials for regenerative medical applications, the need for their safety assessment is paramount. A porcine cholecyst-derived scaffold (CDS), intended as a muscle repair graft, prepared by a nondetergent/enzymatic method was engrafted in a rat abdominal wall defect model. Host tissue-scaffold interface samples were collected 2, 8, and 16 weeks postimplantation and evaluated by histopathology, immunohistochemistry, and electron microscopy. The nature of the tissue reaction was compared with those induced by a jejunum-derived scaffold (JDS) prepared by the same method and a commercial-grade small intestinal submucosa (CSIS) scaffold...
January 1, 2018: Toxicologic Pathology
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