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https://www.readbyqxmd.com/read/28736264/mesenchymal-stem-stromal-cell-extracellular-vesicles-from-active-principle-to-next-generation-drug-delivery-system
#1
REVIEW
Barbara Crivelli, Theodora Chlapanidas, Sara Perteghella, Enrico Lucarelli, Luisa Pascucci, Anna Teresa Brini, Ivana Ferrero, Mario Marazzi, Augusto Pessina, Maria Luisa Torre
It has been demonstrated that the biological effector of mesenchymal stem/stromal cells (MSCs) is their secretome, which is composed of a heterogeneous pool of bioactive molecules, partially enclosed in extracellular vesicles (EVs). Therefore, the MSC secretome (including EVs) has been recently proposed as possible alternative to MSC therapy. The secretome can be considered as a protein-based biotechnological product, it is probably safer compared with living/cycling cells, it presents virtually lower tumorigenic risk, and it can be handled, stored and sterilized as an Active Pharmaceutical/Principle Ingredient (API)...
July 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28734802/co-transplantation-of-mesenchymal-and-neural-stem-cells-and-overexpressing-stromal-derived-factor-1-for-treating-spinal-cord-injury
#2
Andrew N Stewart, Griffin Kendziorski, Zachary M Deak, Dara J Brown, Matthew N Fini, Katherine L Copely, Julien Rossignol, Gary L Dunbar
Genetic engineering of mesenchymal stem cells (MSCs) and neuronal stem cells (NSCs) has been used to treat spinal cord injuries (SCI). As a mechanism of therapy, MSCs secrete high amounts of anti-inflammatory cytokines and trophic factors, while NSCs can differentiate into neuronal lineages and aid in tissue replacement. Additionally, the forced overexpression of secreted proteins can enhance the secretome of transplanted cells, which can increase therapeutic efficacy. This study utilized a combinational treatment consisting of MSCs, NSCs, and the forced overexpression of the chemokine stromal-derived factor-1 (SDF-1) from MSCs (SDF-1-MSCs), to treat a rat model of SCI...
July 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28734678/improvement-of-adipose-tissue-derived-cells-by-low-energy-extracorporeal-shock-wave-therapy
#3
Eleni Priglinger, Christina M A P Schuh, Carolin Steffenhagen, Christoph Wurzer, Julia Maier, Sylvia Nuernberger, Wolfgang Holnthoner, Christiane Fuchs, Susanne Suessner, Dominik Rünzler, Heinz Redl, Susanne Wolbank
BACKGROUND: Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency...
July 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28731525/differences-in-stem-cell-processing-lead-to-distinct-secretomes-secretion-implications-for-differential-results-of-previous-clinical-trials-of-stem-cell-therapy-for-myocardial-infarction
#4
Bernhard Wernly, Inês Gonçalves, Attila Kiss, Vera Paar, Tobias Mösenlechner, Michael Leisch, David Santer, Lucas Motloch, Klaus Ulrich Klein, Eva Verena Tretter, Daniel Kretzschmar, Bruno Podesser, Christian Jung, Uta C Hoppe, Michael Lichtenauer
INTRODUCTION: Stem cell therapy for acute myocardial infarction (AMI) seemed to be a promising therapy, however large clinical trials brought differential outcome. It has been shown that paracrine effects of secretomes of stem cells rather than cell therapy might play a fundamental role. The present study sought to compare cell processing protocols of clinical trials and investigated effects of differential cell culture conditions on chemokine secretion and functional effects. METHODS: Different secretomes were compared regarding IL-8, VEGF, MCP-1 and TNF-alpha secretion...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28730487/a-methodology-for-comprehensive-analysis-of-toll-like-receptor-signaling-in-macrophages
#5
Marijke Koppenol-Raab, Aleksandra Nita-Lazar
A combination of high-throughput, multiplexed, quantitative methods with computational modeling and statistical approaches is required to obtain system-level understanding of biological function. Mass spectrometry (MS)-based proteomics has emerged as a preferred tool for the analysis of changes in protein abundance and their post-translational modification (PTM) levels at a global scale, comparable with genomic experiments and generating data suitable for use in mathematical modeling of signaling pathways. Here we describe a set of parallel bottom-up proteomic approaches to detect and quantify the global protein changes in total intracellular proteins, their phosphorylation, and the proteins released by active and passive secretion or shedding mechanisms (referred to as the secretome as reviewed in Makridakis and Vlahou, J Proteome 73:2291-2305, 2010) in response to the stimulation of Toll-like receptors (TLRs) with specific ligands in cultured macrophages...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729727/senescent-cells-an-emerging-target-for-diseases-of-ageing
#6
REVIEW
Bennett G Childs, Martina Gluscevic, Darren J Baker, Remi-Martin Laberge, Dan Marquess, Jamie Dananberg, Jan M van Deursen
Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies...
July 21, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28728879/identification-of-universal-diagnostic-peptide-candidates-for-neglected-tropical-diseases-caused-by-cestodes-through-the-integration-of-multi-genome-wide-analyses-and-immunoinformatic-predictions
#7
Sebastián Miles, Marco Navatta, Sylvia Dematteis, Gustavo Mourglia-Ettlin
Neglected tropical diseases caused by helminth infections currently affect millions of people worldwide. Among them, there are three tapeworm species of outstanding importance: Echinococcus granulosus, E. multilocularis, and Taenia solium, which are responsible for cystic echinococcosis, alveolar echinococcosis, and cysticercosis, respectively. Despite several attempts, there is still a need for an effective and low-cost serological diagnostic test that can be used in endemic countries. In the present work, we described an innovative bioinformatic workflow for a rational prediction of putative peptide candidates for one-step serological diagnosis of any of these infections...
July 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28727618/clinical-study-of-bone-regeneration-by-conditioned-medium-from-mesenchymal-stem-cells-after-maxillary-sinus-floor-elevation
#8
Wataru Katagiri, Junna Watanabe, Naoto Toyama, Masashi Osugi, Kohei Sakaguchi, Hideharu Hibi
OBJECTIVE: This clinical study was undertaken to evaluate the safety of use of the secretome of bone marrow-derived mesenchymal stem cells (MSC-CM) for maxillary sinus floor elevation (SFE). MATERIALS AND METHODS: MSC-CM was prepared from conditioned medium from human bone marrow-derived MSCs. Six partially edentulous patients were enrolled in the study. MSC-CM was mixed with porous beta-tricalcium phosphate (β-TCP) and implanted in 4 patients (experimental group), whereas only β-TCP was implanted in the other 2 patients (control group)...
August 2017: Implant Dentistry
https://www.readbyqxmd.com/read/28718514/aldehyde-dehydrogenase-1-a1-regulates-energy-metabolism-in-adipocytes-from-different-species
#9
Kefeng Yang, Christopher Adin, Qiwen Shen, Ly James Lee, Lianbo Yu, Paolo Fadda, Arpad Samogyi, Kathleen Ham, Lu Xu, Chen Gilor, Ouliana Ziouzenkova
BACKGROUND: Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for interspecies cross talk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes...
July 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28713871/immune-dysfunctionality-of-replicative-senescent-mesenchymal-stromal-cells-is-corrected-by-ifn%C3%AE-priming
#10
Raghavan Chinnadurai, Devi Rajan, Spencer Ng, Kenneth McCullough, Dalia Arafat, Edmund K Waller, Larry J Anderson, Greg Gibson, Jacques Galipeau
Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro. IFNγ does not upregulate HLA-DR on senescent MSCs, whereas its silencing did not reverse fit MSCs' immunosuppressive properties...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/28710827/comparison-of-non-coding-rnas-in-exosomes-and-functional-efficacy-of-human-embryonic-stem-cell-versus-induced-pluripotent-stem-cell-derived-cardiomyocytes
#11
Won Hee Lee, Wenyi Chen, Ning-Yi Shao, Dan Xiao, Xulei Qin, Natalie Baker, Hye Ryeong Michelle Bae, Praveen Shukla, Haodi Wu, Kazuki Kodo, Sang-Ging Ong, Joseph C Wu
BACKGROUND: Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome...
July 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/28710530/proteomic-characterisation-reveals-active-wnt-signalling-by-human-multipotent-stromal-cells-as-a-key-regulator-of-beta-cell-survival-and-proliferation
#12
Miljan Kuljanin, Gillian I Bell, Stephen E Sherman, Gilles A Lajoie, David A Hess
AIMS/HYPOTHESIS: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. METHODS: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC(R)) vs nonregenerative (MSC(NR)) capacity...
July 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28707555/long-term-effects-of-silver-nanoparticles-in-caco-2-cells
#13
Laura Vila, Ricard Marcos, Alba Hernández
The high success of silver nanoparticles (AgNPs), mainly associated with their proved antimicrobial properties, has led to an increasing spread in our close environment. Although many studies have been carried out to detect potential toxicity of AgNPs, most of them have been developed under unrealistic exposure conditions. In terms of human risk, the evaluation of long-term exposures to sub-toxic doses of NPs remains a challenge. Here we have determined different transformation-related end-points under a scenario of 6 weeks long-term exposure to low non-cytotoxic AgNPs concentrations (0...
July 14, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28706242/draft-whole-genome-sequence-of-groundnut-stem-rot-fungus-athelia-rolfsii-revealing-genetic-architect-of-its-pathogenicity-and-virulence
#14
M A Iquebal, Rukam S Tomar, M V Parakhia, Deepak Singla, Sarika Jaiswal, V M Rathod, S M Padhiyar, Neeraj Kumar, Anil Rai, Dinesh Kumar
Groundnut (Arachis hypogaea L.) is an important oil seed crop having major biotic constraint in production due to stem rot disease caused by fungus, Athelia rolfsii causing 25-80% loss in productivity. As chemical and biological combating strategies of this fungus are not very effective, thus genome sequencing can reveal virulence and pathogenicity related genes for better understanding of the host-parasite interaction. We report draft assembly of Athelia rolfsii genome of ~73 Mb having 8919 contigs. Annotation analysis revealed 16830 genes which are involved in fungicide resistance, virulence and pathogenicity along with putative effector and lethal genes...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701751/secretome-of-in-vitro-cultured-human-embryos-contains-extracellular-vesicles-that-are-uptaken-by-the-maternal-side
#15
Elisa Giacomini, Riccardo Vago, Ana Maria Sanchez, Paola Podini, Natasa Zarovni, Valentina Murdica, Roberta Rizzo, Daria Bortolotti, Massimo Candiani, Paola Viganò
Communication between embryo and maternal endometrium occurs during a specific time frame in which implantation is possible. Here we demonstrate for the first time that conditioned media from non-manipulated human embryos cultured in vitro for 3 days or up to the blastocyst stage contain extracellular vesicles (EVs) with a diameter of 50 to 200 nm and bearing the traditional microvesicle and exosome marker proteins CD63, CD9 and ALIX. The embryonic origin of these EVs has been confirmed by the presence of stemness gene transcripts and their enrichment in the non-classical HLA-G protein...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698717/from-blood-to-lesioned-brain-an-in-vitro-study-on-migration-mechanisms-of-human-nasal-olfactory-stem-cells
#16
Stéphane D Girard, Isabelle Virard, Emmanuelle Lacassagne, Jean-Michel Paumier, Hanae Lahlou, Françoise Jabes, Yves Molino, Delphine Stephan, Kevin Baranger, Maya Belghazi, Arnaud Deveze, Michel Khrestchatisky, Emmanuel Nivet, François S Roman, François Féron
Stem cell-based therapies critically rely on selective cell migration toward pathological or injured areas. We previously demonstrated that human olfactory ectomesenchymal stem cells (OE-MSCs), derived from an adult olfactory lamina propria, migrate specifically toward an injured mouse hippocampus after transplantation in the cerebrospinal fluid and promote functional recoveries. However, the mechanisms controlling their recruitment and homing remain elusive. Using an in vitro model of blood-brain barrier (BBB) and secretome analysis, we observed that OE-MSCs produce numerous proteins allowing them to cross the endothelial wall...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28695748/proteomic-profiling-of-the-cancer-cell-secretome-informing-clinical-research
#17
Yung-Chin Hsiao, Lichieh Julie Chu, Jen-Ting Chen, Ta-Sen Yeh, Jau-Song Yu
Cancer represents one of the major causes of human deaths. Identification of proteins as biomarkers for early detection of cancer and therapeutic targets for cancer treatment are important issues in precision medicine. Secretome of cancer cells represents the collection of proteins secreted or shed from cancer cells. Proteomic profiling of the cancer cell secretome has been proven to be a convenient and efficient way to discover cancer biomarker and/or therapeutic targets. Areas covered: There have been numerous reviews describing the history and application of secretome analysis in cancer biomarker/therapeutic target research...
July 11, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28688176/a-novel-role-for-camkk1-in-the-regulation-of-the-mesenchymal-stem-cell-secretome
#18
Feng Dong, Shyam Patnaik, Zhong-Hui Duan, Matthew Kiedrowski, Marc S Penn, Maritza E Mayorga
Transplantation of adult stem cells into myocardial tissue after acute myocardial infarction (AMI), has been shown to improve tissue recovery and prevent progression to ischemic cardiomyopathy. Studies suggest that the effects of mesenchymal stem cells (MSC) are due to paracrine factors released by MSC, as the benefits of MSC can be achieved through delivery of conditioned media (CM) alone. We previously demonstrated that downregulation of Dab2 enhances MSC cardiac protein expression and improves cardiac function after AMI following MSC engraftment...
July 8, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28684402/braf-v600-inhibition-alters-the-microrna-cargo-in-the-vesicular-secretome-of-malignant-melanoma-cells
#19
Taral R Lunavat, Lesley Cheng, Berglind O Einarsdottir, Roger Olofsson Bagge, Somsundar Veppil Muralidharan, Robyn A Sharples, Cecilia Lässer, Yong Song Gho, Andrew F Hill, Jonas A Nilsson, Jan Lötvall
The BRAF inhibitors vemurafenib and dabrafenib can be used to treat patients with metastatic melanomas harboring BRAF(V600) mutations. Initial antitumoral responses are often seen, but drug-resistant clones with reactivation of the MEK-ERK pathway soon appear. Recently, the secretome of tumor-derived extracellular vesicles (EVs) has been ascribed important functions in cancers. To elucidate the possible functions of EVs in BRAF-mutant melanoma, we determined the RNA content of the EVs, including apoptotic bodies, microvesicles, and exosomes, released from such cancer cells after vemurafenib treatment...
July 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28684183/proteomic-approaches-to-decipher-cancer-cell-secretome
#20
REVIEW
Jessica Brandi, Marcello Manfredi, Giulia Speziali, Fabio Gosetti, Emilio Marengo, Daniela Cecconi
In this review, we give an overview of the actual proteomic approaches used in the study of cancer cells secretome. In particular, we describe the proteomic strategies to decipher cancer cell secretome initially focusing on the different aspects of sample preparation. We examine the issues related to the presence of low abundant proteins, the analysis of secreted proteins in the conditioned media with or without the removal of fetal bovine serum and strategies developed to reduce intracellular protein contamination...
July 3, 2017: Seminars in Cell & Developmental Biology
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