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https://www.readbyqxmd.com/read/28524859/mesenchymal-stem-cells-sense-mitochondria-released-from-damaged-cells-as-danger-signals-to-activate-their-rescue-properties
#1
Meriem Mahrouf-Yorgov, Lionel Augeul, Claire Crola Da Silva, Maud Jourdan, Muriel Rigolet, Sylvie Manin, René Ferrera, Michel Ovize, Adeline Henry, Aurélie Guguin, Jean-Paul Meningaud, Jean-Luc Dubois-Randé, Roberto Motterlini, Roberta Foresti, Anne-Marie Rodriguez
Mesenchymal stem cells (MSCs) protect tissues against cell death induced by ischemia/reperfusion insults. This therapeutic effect seems to be controlled by physiological cues released by the local microenvironment following injury. Recent lines of evidence indicate that MSC can communicate with their microenvironment through bidirectional exchanges of mitochondria. In particular, in vitro and in vivo studies report that MSCs rescue injured cells through delivery of their own mitochondria. However, the role of mitochondria conveyed from somatic cells to MSC remains unknown...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28521905/harnessing-the-properties-of-dendritic-cells-in-the-pursuit-of-immunological-tolerance
#2
REVIEW
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild
The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the "holy grail" of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28521131/diverse-requirements-for-microglial-survival-specification-and-function-revealed-by-defined-medium-cultures
#3
Christopher J Bohlen, F Chris Bennett, Andrew F Tucker, Hannah Y Collins, Sara B Mulinyawe, Ben A Barres
Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28514439/haematopoietic-stem-and-progenitor-cells-from-human-pluripotent-stem-cells
#4
Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A Goettel, Erik Serrao, R Grant Rowe, Mohan Malleshaiah, Irene Wong, Patricia Sousa, Ted N Zhu, Andrea Ditadi, Gordon Keller, Alan N Engelman, Scott B Snapper, Sergei Doulatov, George Q Daley
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28514438/conversion-of-adult-endothelium-to-immunocompetent-haematopoietic-stem-cells
#5
Raphael Lis, Charles C Karrasch, Michael G Poulos, Balvir Kunar, David Redmond, Jose G Barcia Duran, Chaitanya R Badwe, William Schachterle, Michael Ginsberg, Jenny Xiang, Arash Rafii Tabrizi, Koji Shido, Zev Rosenwaks, Olivier Elemento, Nancy A Speck, Jason M Butler, Joseph M Scandura, Shahin Rafii
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28512922/effect-of-chemical-immobilization-of-sdf-1%C3%AE-into-muscle-derived-scaffolds-on-angiogenesis-and-muscle-progenitor-recruitment
#6
Sareh Rajabi-Zeleti, Sasan Jalili-Firoozinezhad, Mohammad Kazemi Ashtiani, Gilles Le Carrou, Shahragim Tajbakhsh, Hossein Baharvand
The availability of three-dimensional bioactive scaffolds with enhanced angiogenic capacity that have the capability to recruit tissue specific resident progenitors is of great importance for the regeneration of impaired skeletal muscle. Here we have investigated whether introduction of chemoattractant factors to tissue specific extracellular matrix (ECM) promotes cellular behavior in vitro as well as muscle progenitor recruitment and vascularization in vivo. We developed an interconnective macroporous sponge from decellularized skeletal muscle with maintained biochemical traits of the intact muscle...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28512561/bone-marrow-homing-and-engraftment-defects-of-human-hematopoietic-stem-and-progenitor-cells
#7
REVIEW
Giovanni Caocci, Marianna Greco, Giorgio La Nasa
Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process. In this overview, we analyze the characteristics of stem cells (SCs) with particular emphasis on their plasticity and ability to find their way home to the bone marrow...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28511928/rational-design-of-nanoparticles-towards-targeting-antigen-presenting-cells-and-improved-t-cell-priming
#8
Eva Zupančič, Caterina Curato, Maria Paisana, Catarina Rodrigues, Ziv Porat, Ana S Viana, Carlos A M Afonso, João Pinto, Rogério Gaspar, João N Moreira, Ronit Satchi-Fainaro, Steffen Jung, Helena F Florindo
Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules...
May 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28511675/comparing-adult-renal-stem-cell-identification-characterization-and-applications
#9
REVIEW
Jennifer Huling, James J Yoo
Despite growing interest and effort, a consensus has yet to be reached in regards to the identification of adult renal stem cells. Organ complexity and low turnover of renal cells has made stem cell identification difficult and lead to the investigation of multiple possible populations. In this review, we summarize the work that has been done toward finding and characterizing an adult renal stem cell population. In addition to giving a general overview of what has been done, we aim to highlight the variation in methods and outcomes...
May 16, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28507812/a-barf1-specific-mab-as-a-new-immunotherapeutic-tool-for-the-management-of-ebv-related-tumors
#10
Riccardo Turrini, Anna Merlo, Debora Martorelli, Damiana Antonia Faè, Roberta Sommaggio, Isabella Monia Montagner, Vito Barbieri, Oriano Marin, Paola Zanovello, Riccardo Dolcetti, Antonio Rosato
The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507545/clinical-and-molecular-heterogeneity-of-rtel1-deficiency
#11
Carsten Speckmann, Sushree Sangita Sahoo, Marta Rizzi, Shinsuke Hirabayashi, Axel Karow, Nina Kathrin Serwas, Marc Hoemberg, Natalja Damatova, Detlev Schindler, Jean-Baptiste Vannier, Simon J Boulton, Ulrich Pannicke, Gudrun Göhring, Kathrin Thomay, J J Verdu-Amoros, Holger Hauch, Wilhelm Woessmann, Gabriele Escherich, Eckart Laack, Liliana Rindle, Maximilian Seidl, Anne Rensing-Ehl, Ekkehart Lausch, Christine Jandrasits, Brigitte Strahm, Klaus Schwarz, Stephan R Ehl, Charlotte Niemeyer, Kaan Boztug, Marcin W Wlodarski
Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28506845/ex-vivo-mesenchymal-precursor-cell-expanded-cord-blood-transplantation-following-reduced-intensity-conditioning-regimens-improves-time-to-neutrophil-recovery
#12
Rohtesh S Mehta, Rima M Saliba, Kai Cao, Indreshpal Kaur, Katy Rezvani, Julianne Chen, Amanda Olson, Simrit Parmar, Nina Shah, David Marin, Amin Alousi, Chitra Hosing, Uday Popat, Partow Kebriaei, Richard Champlin, Marcos de Lima, Donna Skerrett, Elizabeth Burke, Elizabeth J Shpall, Betul Oran
We previously showed the safety of using cord blood (CB) expanded ex vivo in cocultures with allogeneic mesenchymal precursor cells (MPC) after myeloablative conditioning with faster recovery of neutrophils and platelets compared with historical controls. Herein, we report the transplant outcomes of 27 patients with hematologic cancers who received one CB unit ex vivo expanded with MPCs in addition to an unmanipulated CB (MPC group) after reduced intensity conditioning (RIC). The results in this group were compared with 51 historical controls who received two unmanipulated CB units (control group)...
May 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28506317/changes-in-microbial-ecology-after-fecal-microbiota-transplantation-for-recurrent-c-difficile-infection-affected-by-underlying-inflammatory-bowel-disease
#13
Sahil Khanna, Yoshiki Vazquez-Baeza, Antonio González, Sophie Weiss, Bradley Schmidt, David A Muñiz-Pedrogo, John F Rainey, Patricia Kammer, Heidi Nelson, Michael Sadowsky, Alexander Khoruts, Stefan L Farrugia, Rob Knight, Darrell S Pardi, Purna C Kashyap
BACKGROUND: Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD...
May 15, 2017: Microbiome
https://www.readbyqxmd.com/read/28501849/mir-551b-regulates-epithelial-mesenchymal-transition-and-metastasis-of-gastric-cancer-by-inhibiting-erbb4-expression
#14
Guangyuan Song, Hongcheng Zhang, Chenlin Chen, Lijie Gong, Biao Chen, Shaoyun Zhao, Ji Shi, Ji Xu, Zaiyuan Ye
Epithelial-mesenchymal transition (EMT) is an important biological process that is characteristic of malignant tumor cells with metastatic potential. We investigated the role of miR-551b in EMT and metastasis in gastric cancer (GC). We found that low miR-551b levels were associated with EMT, metastasis and a poor prognosis in GC patients. Further, two GC cell lines, MNK45 and SGC7901, exhibited lower miR-551b levels than the GES normal stomach cell line. Exposing MNK45 and SGC7901 cells to TGF-β1 resulted in cell morphology changes characteristic of EMT, which was confirmed by western blot analysis demonstrating low E-Cadherin and high N-Cadherin and Vimentin levels...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28501622/the-role-of-plasmin-in-the-pathogenesis-of-murine-multiple-myeloma
#15
Salita Eiamboonsert, Yousef Salama, Hiroshi Watarai, Douaa Dhahri, Yuko Tsuda, Yoshio Okada, Koichi Hattori, Beate Heissig
Aside from a role in clot dissolution, the fibrinolytic factor, plasmin is implicated in tumorigenesis. Although abnormalities of coagulation and fibrinolysis have been reported in multiple myeloma patients, the biological roles of fibrinolytic factors in multiple myeloma (MM) using in vivo models have not been elucidated. In this study, we established a murine model of fulminant MM with bone marrow and extramedullar engraftment after intravenous injection of B53 cells. We found that the fibrinolytic factor expression pattern in murine B53 MM cells is similar to the expression pattern reported in primary human MM cells...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28501125/direct-orthotopic-implantation-of-hepatic-organoids
#16
Vivian X Zhou, Macarena Lolas, Tammy T Chang
BACKGROUND: Liver organoids show potential for development as a tissue replacement therapy for patients with end-stage liver disease, but efficient methods for introducing organoids into host livers have not been established. In this study, we aimed to develop a surgical technique to implant hepatic organoids into the liver and assess their engraftment. METHODS: Donor hepatocytes were isolated from ROSA26 C57BL/6 mice, so that engrafted cells, when implanted into wild-type mice, could be easily identified by X-gal staining...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28499937/haploidentical-allogeneic-hematopoietic-cell-transplantation-for-multiple-myeloma-using-post-transplant-cyclophosphamide-gvhd-prophylaxis
#17
Luca Castagna, Alberto Mussetti, Raynier Devillier, Alida Dominietto, Magda Marcatti, Giuseppe Milone, Francesco Maura, Chiara de Philippis, Benedetto Bruno, Sabine Furst, Didier Blaise, Paolo Corradini, Vittorio Montefusco
Allogeneic Hematopoietic Cell Transplantation (allo-HCT) currently represents the only potentially curative therapy for patients affected by multiple myeloma (MM). Up to 30% of patients in western countries do not have a matched donor. Haploidentical HCT (haplo-HCT) may be an option, but currently, there is are available data regarding this treatment. We analyzed survival outcomes of 30 heavily pretreated MM patients who received haplo-HCT with post-transplant cyclophosphamide (PT-Cy) as graft-versus-host-disease (GVHD) prophylaxis...
May 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28499936/ucbt-without-antithymocyte-globulin-results-in-similar-survival-but-better-quality-of-life-compared-with-upbsct-for-the-treatment-of-acute-leukemia-a-retrospective-study-in-china
#18
J Tong, L Xuan, Y L Sun, D P Huang, H L Liu, C C Zheng, X Y Zhu, B L Tang, K D Song, X H Zhang, L Zhang, W Yao, D J Lin, Q F Liu, Z M Sun
While previous studies have demonstrated improved outcomes in umbilical cord blood transplantation (UCBT) by omitting antithymocyte globulin (ATG) in the conditioning regimen, this approach has not been comparatively studied in unrelated peripheral blood stem cell transplantation (UPBSCT). To compare the risks and benefits between UCBT without ATG and UPBSCT in patients with acute leukemia (AL). This was a multicenter retrospective study of 79 patients who underwent UCBT (myeloablative conditioning without ATG) and 96 patients who underwent UPBSCT (myeloablative conditioning with ATG)...
May 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28498996/protective-factors-in-the-intestinal-microbiome-against-clostridium-difficile-infection-in-recipients-of-allogeneic-hematopoietic-stem-cell-transplantation
#19
Yeon Joo Lee, Esther S Arguello, Robert R Jenq, Eric Littmann, Grace J Kim, Liza C Miller, Lilan Ling, Cesar Figueroa, Elizabeth Robilotti, Miguel-Angel Perales, Juliet N Barker, Sergio Giralt, Marcel R M van den Brink, Eric G Pamer, Ying Taur
Background: Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI after engraftment. Methods: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed from each sample...
April 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28498863/notch-ligands-regulate-the-muscle-stem-like-state-ex-vivo-but-are-not-sufficient-for-retaining-regenerative-capacity
#20
Hiroshi Sakai, Sumiaki Fukuda, Miki Nakamura, Akiyoshi Uezumi, Yu-Taro Noguchi, Takahiko Sato, Mitsuhiro Morita, Harumoto Yamada, Kunihiro Tsuchida, Shahragim Tajbakhsh, So-Ichiro Fukada
Myogenic stem cells are a promising avenue for the treatment of muscular disorders. Freshly isolated muscle stem cells have a remarkable engraftment ability in vivo, but their cell number is limited. Current conventional culture conditions do not allow muscle stem cells to expand in vitro with their bona fide engraftment efficiency, requiring the improvement of culture procedures for achieving successful cell-therapy for muscle disorders. Here we expanded mouse muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to activate Notch signaling in vitro and to investigate whether these cells could retain their engraftment efficiency...
2017: PloS One
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