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1. Wharton’s Jelly Mesenchymal Stromal Cells and Derived Extracellular Vesicles as Post-Myocardial Infarction Therapeutic Toolkit: An Experienced View

Author

Muñoz-Domínguez, Noelia, Roura, Santiago, Prat-Vidal, Cristina, Vives Armengol, Joaquim, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Muñoz-Domínguez N] Servei de Teràpia Cel·lular, Banc de Sang i Teixits, Barcelona, Spain. [Roura S] ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Can Ruti Campus, Badalona, Spain. Heart Institute (iCor), Germans Trias i Pujol University Hospital, Badalona, Spain. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. Faculty of Medicine, University of Vic-Central University of Catalonia, Vic, Spain. [Prat-Vidal C] ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Can Ruti Campus, Badalona, Spain. Heart Institute (iCor), Germans Trias i Pujol University Hospital, Badalona, Spain. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. Institut d’Investigació Biomèdica de Bellvitge—IDIBELL, L’Hospitalet de Llobregat, Spain. [Vives J] Servei de Teràpia Cel·lular, Banc de Sang i Teixits, Barcelona, Spain. Grup d'Enginyeria de Teixits Musculoesquelètics, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
biomanufacturing, Cell, Mesenchymal stromal cells, Pharmaceutical Science, Context (language use), Review, Cardiac tissue engineering, Extracellular vesicles, clinical translation, Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction [DISEASES], cardiac tissue engineering, Pharmacy and materia medica, Tissue engineering, Wharton's jelly, medicine, Extracellular, Cells::Cellular Structures::Extracellular Space::Extracellular Vesicles [ANATOMY], Myocardial infarction, Infart de miocardi - Tractament, células::células del tejido conectivo::células del estroma::células madre mesenquimatosas [ANATOMÍA], Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stem Cells [ANATOMY], Biomanufacturing, Wharton’s jelly, business.industry, Clinical translation, Teràpia cel·lular, Mesenchymal stem cell, células::estructuras celulares::espacio extracelular::vesículas extracelulares [ANATOMÍA], medicine.disease, enfermedades cardiovasculares::enfermedades cardíacas::isquemia miocárdica::infarto de miocardio [ENFERMEDADES], RS1-441, medicine.anatomical_structure, myocardial infarction, Cancer research, business, extracellular vesicles, mesenchymal stromal cells
Abstract

Gelatina de Wharton; Enginyeria de teixits cardíacs; Infart de miocardi Gelatina de Wharton; Ingeniería de tejidos cardíacos; Infarto de miocardio Wharton’s jelly; Cardiac tissue engineering; Myocardial infarction Outstanding progress has been achieved in developing therapeutic options for reasonably alleviating symptoms and prolonging the lifespan of patients suffering from myocardial infarction (MI). Current treatments, however, only partially address the functional recovery of post-infarcted myocardium, which is in fact the major goal for effective primary care. In this context, we largely investigated novel cell and TE tissue engineering therapeutic approaches for cardiac repair, particularly using multipotent mesenchymal stromal cells (MSC) and natural extracellular matrices, from pre-clinical studies to clinical application. A further step in this field is offered by MSC-derived extracellular vesicles (EV), which are naturally released nanosized lipid bilayer-delimited particles with a key role in cell-to-cell communication. Herein, in this review, we further describe and discuss the rationale, outcomes and challenges of our evidence-based therapy approaches using Wharton’s jelly MSC and derived EV in post-MI management. This work has been developed in the context of ADVANCE(CAT) with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) and the European Community under the Catalonian ERDF operational program (European Regional Development Fund) 2014–2020, Generalitat de Catalunya (Departament de Salut) PERIS Acció Instrumental de Programes de Recerca Orientats (SLT002/16/00234), Spanish Society of Cardiology, Catalan Society of Cardiology, Fundació bancària La Caixa, CIBER Cardiovascular (CB16/11/00403) and by the Spanish Cell Therapy Network (TerCel, expedient numbers: RD16/0011/0006 & RD16/0011/0028). Projects PI19/01788, PI17/01487, PIC18/00014, ICI19/00039, PI18/00256, PI18/01227, ICI20/00135 are funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF)—A way to build Europe. Projects SAF2017-84324-C2-1-R and PID2019-110137RB-I00 are funded the Spanish Ministry of Economy and Competitiveness-MICINN. Our laboratories are awarded by the Generalitat de Catalunya’s AGAUR as Consolidated Research Groups (references 2017-SGR-483, 2017-SGR-719 and 2019PROD00122), and by the Catalan Heath Institute.

Published
2021

2. Determination of HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in heart failure patients

Author

Institut Català de la Salut, [Roura S] ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Badalona, Spain. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. [Rudilla F] Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain. Grup en medicina transfusional, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Gastelurrutia P] ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Badalona, Spain. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. [Enrich E] Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain. Grup en medicina transfusional, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Campos E] Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain. [Lupón J] CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain. Department of Medicine, UAB, Barcelona, Spain., and Hospital Universitari Vall d'Hebron

Subjects
Cardiovascular Diseases::Heart Diseases::Heart Failure [DISEASES], Enfermedades Cardiovasculares::Cardiopatías::Insuficiencia Cardíaca [ENFERMEDADES], Otros calificadores::Otros calificadores::/genética [Otros calificadores], Insuficiència cardíaca - Aspectes genètics, Teràpia cel·lular, Other subheadings::Other subheadings::/genetics [Other subheadings], Genetic Phenomena::Genotype::Haplotypes [PHENOMENA AND PROCESSES], Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT], Fenómenos Genéticos::Genotipo::Haplotipos [FENÓMENOS Y PROCESOS], Terapéutica::Terapia Biológica::Tratamiento Basado en Trasplante de Células y Tejidos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
Published
2021

3. Assessment of inner retinal layers and choroidal thickness in type 1 diabetes mellitus: a cross-sectional study

Author

Institut Català de la Salut, [Carbonell M] Department of Ophthalmology, University Hospital Germans Trias i Pujol, Badalona, Spain. Department of Surgery, Barcelona Autonomous University (UAB), Barcelona, Spain. [Alonso N] Department of Endocrinology and Nutrition, University Hospital and Health Science Research Institute Germans Trias i Pujol, Badalona, Spain. Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain. [Castelblanco E] Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau & Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain. DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. [Real J] Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. [Ramírez-Morros A] Department of Endocrinology and Nutrition, University Hospital and Health Science Research Institute Germans Trias i Pujol, Badalona, Spain. [Simó R, Hernández C] ] Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Servei d’Endocrinologia i Nutrició, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, and Hospital Universitari Vall d'Hebron

Subjects
Diabetis - Investigació, técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios transversales [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Angiopathies::Diabetic Retinopathy [DISEASES], Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 1 [DISEASES], enfermedades del sistema endocrino::diabetes mellitus::diabetes mellitus tipo I [ENFERMEDADES], Enfermedades del Sistema Endocrino::Diabetes Mellitus::Complicaciones de la Diabetes::Angiopatías Diabéticas::Retinopatía Diabética [ENFERMEDADES], Retinopatia diabètica, Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Cross-Sectional Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Published
2021

4. Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction

Author

Francesc E. Borràs, S. Roura, Adriana Cserkóová, Paloma Gastelurrutia, Miriam Morón-Font, Anna Rosell, Carolina Gálvez-Montón, Alexandra Calle, Marta Monguió-Tortajada, Anna Morancho, Antoni Bayes-Genis, Marta Clos-Sansalvador, Miguel Ángel Ramírez, Cristina Prat-Vidal, Institut Català de la Salut, [Monguió-Tortajada M] ICREC Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Can Ruti Campus, Badalona, Spain. REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Can Ruti Campus, Badalona, Spain. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. [Prat-Vidal C, Gastelurrutia P] ICREC Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Can Ruti Campus, Badalona, Spain. CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. Institut d’Investigació Biomèdica de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Spain. [Moron-Font M] REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Can Ruti Campus, Badalona, Spain. [Clos-Sansalvador M] REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Can Ruti Campus, Badalona, Spain. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Calle A] Departamento de Reproducción Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain. [Morancho A, Rosell A] Laboratori d'Investigació Neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
QH301-705.5, Angiogenesis, 0206 medical engineering, Biomedical Engineering, Adipose tissue, Inflammation, 02 engineering and technology, Cardiac tissue engineering, Exosomes, Article, Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction [DISEASES], Biomaterials, Otros calificadores::Otros calificadores::Otros calificadores::/trasplante [Otros calificadores], In vivo, Cells::Cellular Structures::Extracellular Space::Extracellular Vesicles [ANATOMY], medicine, Macrophage, Miocardi - Regeneració, Tissue engineering, Infart de miocardi - Tractament, Biology (General), Materials of engineering and construction. Mechanics of materials, Otros calificadores::/terapia [Otros calificadores], Migration, Other subheadings::Other subheadings::Other subheadings::/transplantation [Other subheadings], Mesenchymal stem/stromal cells, Chemistry, células::estructuras celulares::espacio extracelular::vesículas extracelulares [ANATOMÍA], Mesenchymal stem cell, Infiltration, Other subheadings::/therapy [Other subheadings], 021001 nanoscience & nanotechnology, 020601 biomedical engineering, enfermedades cardiovasculares::enfermedades cardíacas::isquemia miocárdica::infarto de miocardio [ENFERMEDADES], Microvesicles, Cell biology, Infart de miocardi, Myocardial infarction, Enginyeria de teixits, TA401-492, Tumor necrosis factor alpha, medicine.symptom, 0210 nano-technology, Biotechnology
Abstract

The administration of extracellular vesicles (EV) from mesenchymal stromal cells (MSC) is a promising cell-free nanotherapy for tissue repair after myocardial infarction (MI). However, the optimal EV delivery strategy remains undetermined. Here, we designed a novel MSC-EV delivery, using 3D scaffolds engineered from decellularised cardiac tissue as a cell-free product for cardiac repair. EV from porcine cardiac adipose tissue-derived MSC (cATMSC) were purified by size exclusion chromatography (SEC), functionally analysed and loaded to scaffolds. cATMSC-EV markedly reduced polyclonal proliferation and pro-inflammatory cytokines production (IFNγ, TNFα, IL12p40) of allogeneic PBMC. Moreover, cATMSC-EV recruited outgrowth endothelial cells (OEC) and allogeneic MSC, and promoted angiogenesis. Fluorescently labelled cATMSC-EV were mixed with peptide hydrogel, and were successfully retained in decellularised scaffolds. Then, cATMSC-EV-embedded pericardial scaffolds were administered in vivo over the ischemic myocardium in a pig model of MI. Six days from implantation, the engineered scaffold efficiently integrated into the post-infarcted myocardium. cATMSC-EV were detected within the construct and MI core, and promoted an increase in vascular density and reduction in macrophage and T cell infiltration within the damaged myocardium. The confined administration of multifunctional MSC-EV within an engineered pericardial scaffold ensures local EV dosage and release, and generates a vascularised bioactive niche for cell recruitment, engraftment and modulation of short-term post-ischemic inflammation., Graphical abstract Image 1, Highlights • A bioactive engineered scaffold can locally deliver EV to the infarcted myocardium. • Porcine cATMSC-EV promote endothelial cell recruitment and in vivo vascularization. • Porcine cATMSC-EV reduce inflammation, and macrophage and T cell infiltration.

Published
2021

5. Determination of HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in heart failure patients

Author

Josep Lupón, Paloma Gastelurrutia, Eva Campos, Francesc Rudilla, Santiago Roura, Emma Enrich, Evelyn Santiago-Vacas, Sergi Querol, Antoni Bayes-Genis, Institut Català de la Salut, [Roura S] ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Badalona, Spain. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. [Rudilla F] Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain. Grup en medicina transfusional, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Gastelurrutia P] ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Badalona, Spain. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. [Enrich E] Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain. Grup en medicina transfusional, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Campos E] Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain. [Lupón J] CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain. Department of Medicine, UAB, Barcelona, Spain., Vall d'Hebron Barcelona Hospital Campus, and Hospital Universitari Vall d'Hebron

Subjects
Male, Cell- and Tissue-Based Therapy, 030204 cardiovascular system & hematology, 0302 clinical medicine, Gene Frequency, Original Research Articles, Medicine, HLA-DQ beta-Chains, 030212 general & internal medicine, Original Research Article, education.field_of_study, Allele frequency, Otros calificadores::Otros calificadores::/genética [Otros calificadores], fenómenos genéticos::genotipo::haplotipos [FENÓMENOS Y PROCESOS], HLA-A, Terapéutica::Terapia Biológica::Tratamiento Basado en Trasplante de Células y Tejidos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Enfermedades Cardiovasculares::Cardiopatías::Insuficiencia Cardíaca [ENFERMEDADES], Cohort, Haplotype frequency, Female, Cardiology and Cardiovascular Medicine, Genotype, Cardiovascular Diseases::Heart Diseases::Heart Failure [DISEASES], Population, Heart failure, Human leukocyte antigen, HLA-C Antigens, 03 medical and health sciences, Insuficiència cardíaca - Aspectes genètics, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, Allele, education, Alleles, Aged, Heart Failure, HLA-A Antigens, business.industry, Teràpia cel·lular, Haplotype, Allogeneic cell therapy, Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT], enfermedades cardiovasculares::enfermedades cardíacas::insuficiencia cardíaca [ENFERMEDADES], Genotype frequency, Haplotypes, HLA-B Antigens, Immunology, Genetic Phenomena::Genotype::Haplotypes [PHENOMENA AND PROCESSES], business, terapéutica::terapia biológica::tratamientos basados en células y tejidos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], HLA-DRB1 Chains
Abstract

Allogeneic cell therapy; Haplotype frequency; Heart failure Teràpia cel·lular al·logènica; Freqüència haplotípica; Insuficiència cardíaca Terapia celular alogénica; Frecuencia haplotípica; Insuficiencia cardíaca AIMS: Cell therapy can be used to repair functionally impaired organs and tissues in humans. Although autologous cells have an immunological advantage, it is difficult to obtain high cell numbers for therapy. Well-characterized banks of cells with human leukocyte antigens (HLA) that are representative of a given population are thus needed. The present study investigates the HLA allele and haplotype frequencies in a cohort of heart failure (HF) patients. METHODS AND RESULTS: We carried out the HLA typing and the allele and haplotype frequency analysis in 247 ambulatory HF patients. We determined HLA class I (A, B, and C) and class II (DRB1 and DQB1) using next-generation sequencing technology. The allele frequencies were obtained using Python for Population Genomics (PyPop) software, and HLA haplotypes were estimated using HaploStats. A total of 30 HLA-A, 56 HLA-B, 23 HLA-C, 36 HLA-DRB1, and 15 HLA-DQB1 distinct alleles were identified within the studied cohort. The genotype frequencies of all five HLA loci were in Hardy-Weinberg equilibrium. We detected differences in HLA allele frequencies among patients when the etiological cause of HF was considered. There were a total of 494 five-loci haplotypes, five of which were present six or more times. Moreover, the most common estimated HLA haplotype was HLA-A*01:01, HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, and HLA-DQB1*02:01 (6.07% haplotype frequency per patient). Remarkably, the 11 most frequent haplotypes would cover 31.17% of the patients of the cohort in need of allogeneic cell therapy. CONCLUSIONS: Our findings could be useful for improving allogeneic cell administration outcomes without concomitant immunosuppression.

Published
2019

6. Osteogenic commitment of Wharton's jelly mesenchymal stromal cells: mechanisms and implications for bioprocess development and clinical application

Author

Ana Gámez-Valero, Santiago Roura, Raquel Rojas-Márquez, Francesc E. Borràs, Raquel Cabrera-Pérez, Marta Monguió-Tortajada, Joaquim Vives, Institut Català de la Salut, [Cabrera-Pérez R] Cell Therapy Service, Blood and Tissue Bank (BST), Barcelona, Catalonia, Spain. Grup Enginyeria Tissular Musculoesquelètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Monguió-Tortajada M, Gámez-Valero A] REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Catalonia, Spain. [Rojas-Márquez R] Cell Therapy Service, Blood and Tissue Bank (BST), Barcelona, Catalonia, Spain. Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. [Borràs FE] REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Catalonia, Spain. Nephrology Service, Germans Trias i Pujol University Hospital, Badalona, Catalonia, Spain. [Roura S] ICREC Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Catalonia, Spain. [Vives J] Cell Therapy Service, Blood and Tissue Bank (BST), Barcelona, Catalonia, Spain. Grup Enginyeria Tissular Musculoesquelètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Proteomics, Cell, fenómenos fisiológicos nerviosos y musculoesqueléticos::fenómenos fisiológicos musculoesqueléticos::desarrollo musculoesquelético::biomineralización::desarrollo óseo::osteogénesis [FENÓMENOS Y PROCESOS], Mesenchymal stromal cells, Bone Morphogenetic Protein 2, Medicine (miscellaneous), Bone Marrow Cells, Biology, Real-Time Polymerase Chain Reaction, Biochemistry, Genetics and Molecular Biology (miscellaneous), Bone morphogenetic protein 2, Regenerative medicine, Ossos - Creixement, lcsh:Biochemistry, Osteogenesis, Osteogenic differentiation, Wharton's jelly, medicine, Humans, lcsh:QD415-436, Bone marrow, Bone regeneration, lcsh:R5-920, Wharton’s jelly, Cèl·lules de la medul·la òssia, Research, Mesenchymal stem cell, Cell Differentiation, Mesenchymal Stem Cells, Cell Biology, células::células de la médula ósea [ANATOMÍA], medicine.anatomical_structure, Culture Media, Conditioned, Cancer research, Molecular Medicine, Stem cell, Cells::Bone Marrow Cells [ANATOMY], lcsh:Medicine (General), Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Development::Biomineralization::Bone Development::Osteogenesis [PHENOMENA AND PROCESSES]
Abstract

Cèl·lules estromals mesenquimals; Gelatina de Wharton; Diferenciació osteogènica Células estromales mesenquimales; Gelatina de Wharton; Diferenciación osteogénica Mesenchymal stromal cells, Wharton’s jelly; Osteogenic differentiation Background Orthopaedic diseases are one of the major targets for regenerative medicine. In this context, Wharton’s jelly (WJ) is an alternative source to bone marrow (BM) for allogeneic transplantation since its isolation does not require an invasive procedure for cell collection and does not raise major ethical concerns. However, the osteogenic capacity of human WJ-derived multipotent mesenchymal stromal cells (MSC) remains unclear. Methods Here, we compared the baseline osteogenic potential of MSC from WJ and BM cell sources by cytological staining, quantitative real-time PCR and proteomic analysis, and assessed chemical and biological strategies for priming undifferentiated WJ-MSC. Concretely, different inhibitors/activators of the TGFβ1-BMP2 signalling pathway as well as the secretome of differentiating BM-MSC were tested. Results Cytochemical staining as well as gene expression and proteomic analysis revealed that osteogenic commitment was poor in WJ-MSC. However, stimulation of the BMP2 pathway with BMP2 plus tanshinone IIA and the addition of extracellular vesicles or protein-enriched preparations from differentiating BM-MSC enhanced WJ-MSC osteogenesis. Furthermore, greater outcome was obtained with the use of conditioned media from differentiating BM-MSC. Conclusions Altogether, our results point to the use of master banks of WJ-MSC as a valuable alternative to BM-MSC for orthopaedic conditions. Work in our laboratory is supported by the Spanish Cell Therapy Network (TerCel, expedient No. RD16/0011/0028 and RD16/00111/0006), Ministerio de Ciencia Innovación y Universidades de España (Instituto de Salud Carlos III, expedient No. PI19/01788), Fundació la Marató de TV3 (expedient number: 122831), and ISCIII-REDinREN (RD16/0009 Feder Funds), and developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian ERDF operational programme (European Regional Development Fund) 2014-2020. FEB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Generalitat de Catalunya). Our laboratory is awarded by the Generalitat de Catalunya as Consolidated Research Groups (ref. 2017-SGR-719, 2017-SGR-301 and 2017-SGR-483).

Published
2019

7. Assessment of Inner Retinal Layers and Choroidal Thickness in Type 1 Diabetes Mellitus: A Cross-Sectional Study

Author

Esmeralda Castelblanco, Rafael Simó, Xavier Valldeperas, Cristina Hernández, Carme Jurjo, Alicia Traveset, Anna Ramírez-Morros, Didac Mauricio, M. Carbonell, Jordi Real, Núria Alonso, Institut Català de la Salut, [Carbonell M] Department of Ophthalmology, University Hospital Germans Trias i Pujol, Badalona, Spain. Department of Surgery, Barcelona Autonomous University (UAB), Barcelona, Spain. [Alonso N] Department of Endocrinology and Nutrition, University Hospital and Health Science Research Institute Germans Trias i Pujol, Badalona, Spain. Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain. [Castelblanco E] Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau & Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain. DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. [Real J] Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. [Ramírez-Morros A] Department of Endocrinology and Nutrition, University Hospital and Health Science Research Institute Germans Trias i Pujol, Badalona, Spain. [Simó R, Hernández C] ] Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Servei d’Endocrinologia i Nutrició, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
choroidal thickness, Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Angiopathies::Diabetic Retinopathy [DISEASES], estimated glomerular filtration rate, endocrine system diseases, Cross-sectional study, type 1 diabetes, lcsh:Medicine, Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Cross-Sectional Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], retinal ganglion cell layer, low density lipoprotein cholesterol, chemistry.chemical_compound, 0302 clinical medicine, high density lipoprotein cholesterol, Diabetic retinopathy, glucose, hemoglobin A1c, ganglion cell layer, Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 1 [DISEASES], adult, creatinine, General Medicine, Control subjects, laser coagulation, retinal nerve fibre layer, técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios transversales [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], diabetic retinopathy, female, spectral domain optical coherence tomography, medicine.anatomical_structure, Type 1 diabetes, triacylglycerol, enfermedades del sistema endocrino::diabetes mellitus::complicaciones de la diabetes::angiopatías diabéticas::retinopatía diabética [ENFERMEDADES], medicine.medical_specialty, Ganglion cell layer, hypertension, enfermedades del sistema endocrino::diabetes mellitus::diabetes mellitus tipo I [ENFERMEDADES], retinal nerve fiber layer thickness, 030209 endocrinology & metabolism, insulin dependent diabetes mellitus, Article, 03 medical and health sciences, male, Ophthalmology, medicine, cross-sectional study, controlled study, human, myopia, albumin, Diabetis - Investigació, Retina, macular edema, business.industry, Choroid, dyslipidemia, lcsh:R, Retinal, Retinal nerve fibre layer, medicine.disease, major clinical study, body mass, glaucoma, chemistry, eye inflammation, Retinopatia diabètica, 030221 ophthalmology & optometry, sense organs, Bruch membrane, business, choroid
Abstract

Recent studies have shown that retinal neurodegeneration may precede visible vascular changes in diabetic retinopathy (DR). In addition, the relationship of choroidal thickness (CT) with DR stage is not well defined. To assess the inner retinal and choroidal structural changes in type 1 diabetic subjects (T1D), a cross-sectional study was conducted in 242 T1D patients and in 69 age-matched, non-diabetic individuals. The nasal retinal nerve fibre layer (RNFL) thickness was lower in T1D patients without DR (p &lt, 0.001), with mild DR (p &lt, 0.001), and with advanced DR (p &lt, 0.001) compared to control subjects. The ganglion cell layer (GCL) thickness was lower in T1D patients with advanced DR compared to those with mild DR (p = 0.003) and without DR (p &lt, 0.001) and compared to the control subjects (p &lt, 0.001). T1D subjects with no DR and mild DR had higher CT than the control subjects, but the CT in T1D patients with advanced DR was lower (p = 0.038) than that in T1D subjects with mild DR and was not significantly different from that of the control subjects. In conclusion, T1D subjects showed a significant thinning of the nasal RNFL in the early stages of the disease, even before any vascular changes in the retina. A decrease in the GCL thickness during advanced DR stages was observed. Choroidal thickness was higher in T1D subjects without DR and in early DR stages but decreased in advanced stages.

Published
2019

8. Glioblastoma Bystander Cell Therapy: Improvements in Treatment and Insights into the Therapy Mechanisms

Author

Lourdes Sánchez-Cid, Nuria Rubio, Carolina Soler-Botija, José Becerra, Carolina Nogueira de Moraes, Olaia F. Vila, Sara Ramos-Romero, Marta Guerra-Rebollo, Jerónimo Blanco, Cristina Alcoholado, Cristina Garrido, Óscar Meca-Cortés, Ministerio de Economía y Competitividad (España), Catalonian Institute for Advanced Chemistry (IQAC-CSIC), Biomaterials and Nanomedicine (CIBER-BBN), Universidade Estadual Paulista (Unesp), Biomedical Research Institute of Málaga (IBIMA), Health Science Research Institute Germans Trias i Pujol, Carlos III Health Institute, Columbia University, University of Barcelona, and Málaga

Subjects
0301 basic medicine, Cancer Research, Cells, Therapeutic Procedure, lcsh:RC254-282, Article, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, in vivo glioblastoma model, Neoplasms, Bystander effect, glioblastoma bystander therapy, Cytotoxic T cell, Bioluminescence imaging, Medicine, Pharmacology (medical), clarity, mesenchymal stem cell, HVS-thymidine kinase, Mesenchymal Stromal Cells, business.industry, Mesenchymal stem cell, Extracellular vesicle, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, bioluminescence, Tumor Debulking, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, transparent brain, extracellular vesicle, cell therapy, business
Abstract

A preclinical model of glioblastoma (GB) bystander cell therapy using human adipose mesenchymal stromal cells (hAMSCs) is used to address the issues of cell availability, quality, and feasibility of tumor cure. We show that a fast proliferating variety of hAMSCs expressing thymidine kinase (TK) has therapeutic capacity equivalent to that of TK-expressing hAMSCs and can be used in a multiple-inoculation procedure to reduce GB tumors to a chronically inhibited state. We also show that up to 25% of unmodified hAMSCs can be tolerated in the therapeutic procedure without reducing efficacy. Moreover, mimicking a clinical situation, tumor debulking previous to cell therapy inhibits GB tumor growth. To understand these striking results at a cellular level, we used a bioluminescence imaging strategy and showed that tumor-implanted therapeutic cells do not proliferate, are unaffected by GCV, and spontaneously decrease to a stable level. Moreover, using the CLARITY procedure for tridimensional visualization of fluorescent cells in transparent brains, we find therapeutic cells forming vascular-like structures that often associate with tumor cells. In vitro experiments show that therapeutic cells exposed to GCV produce cytotoxic extracellular vesicles and suggest that a similar mechanism may be responsible for the in vivo therapeutic effectiveness of TK-expressing hAMSCs. © 2018 The Author(s), This work was funded by the Spanish Ministry of Science and Innovation (MICINN) (grant SAF2015-64927-C2-1-R), CIBER-BBN, CIBER Cardiovascular (grant CB16/11/00403), Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa TerCel, and the Spanish Ministry of Economy and Competitiveness (MINECO) (grant BIO2015-66266-R). The authors specially thank Dr. Josep Roca from Delfos hospital (Dr. Roca i Noguera aesthetic surgery team) for the kind donation of liposuction for hAMSCs preparation, and to the services of cell culture (Catalonian Institute for Advanced Chemistry-Spanish National Research Council [IQAC-CISC]), animal care (IQAC-CSIC), cell sorting (Scientific and Technological Centers [CCiT]-University of Barcelona), confocal microscopy (CCiT-University of Barcelona), and Central Services for Research Support (SCAI) at the University of Málaga for their technician and specialized support.

Published
2018

9. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research

Author

Eva De Smedt, Bieke Soen, Marta Monguió-Tortajada, Jasper Anckaert, Erminia Romano, Els Beghein, Hina Kalra, Alessandra Lo Cicero, Michael W. Pfaffl, Laurence Bertier, Bert Dhondt, Edward Geeurickx, Özden Akay, Lorraine O'Driscoll, Frederik J. Verweij, Alan Van Goethem, Dominik Buschmann, Olivier De Wever, Zoraida Andreu Martinez, Susanne G. van der Grein, Carina Leonelli, Vincent Hyenne, Shu Liu, Prabhu Mathiyalagan, Guillaume van Niel, Andrew D Foers, Niels Vandamme, Joeri Tulkens, Petra Leidinger, Jan Van Deun, James Brian Byrd, Suzanne Vanhauwaert, David Kim, Patrizia Agostinis, Seyma Demirsoy, Esther N. M. Nolte-‘t Hoen, Stephanie Boukouris, Aleksandra M. Dudek, Michel Bremer, Anna Cmoch, Sandra Kraemer, Kathrin Gärtner, Clotilde Théry, Hetty Helsmoortel, Farzaneh Ghazavi, Pieter Mestdagh, Dillon C. Muth, Jo Vandesompele, Grace V. Hancock, Lien Lippens, Tom Groot Kormelink, Tom A. P. Driedonks, Abdou ElSharawy, Sushma Anand, Marijke I. Zonneveld, Benjamin J. Scicluna, Joanna Kowal, Susmita Sahoo, Lesley Cheng, Safia Thaminy, Isabel Van Audenhove, Suresh Mathivanan, Ilaria Floris, Glenn Vergauwen, Geert Berx, Jan Gettemans, Johannes V. Swinnen, Yaxuan Liang, Victoria Depoorter, Shaun Martin, Alexander R. van Vliet, Natalia G. Sampaio, Martijn J. C. van Herwijnen, Bernd Giebel, Abhishek D. Garg, Bjarke Primdal-Bengtson, An Hendrix, Gloria Milani, Tamás Matusek, Liselot Mus, Annelynn Wallaert, Andrew F. Hill, Roberta Palmulli, Maarit Takatalo, Tine Baetens, Clara Casert, Janneke Boere, Monisha Samuel, Marca H. M. Wauben, Nadine Van Roy, Delphine Daveloose, Anneleen Steels, Andrea Németh, Kenneth W. Witwer, Quentin Rousseau, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Center for Medical Genetics, Cancer Research Institute Ghent (CRIG), Bioinformatics Institute Ghent (BIG), Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain = Catholic University of Louvain (UCL), Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Department of Biochemistry, Faculty of Medicine and Health Sciences, Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University [Utrecht], Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Animal Physiology and Immunology, School of Life Sciences, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Laboratory of Cytometry, Department of Internal Medicine, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Biochemistry, Hôpital Lapeyronie, Institute of Clinical Molecular Biology, Kiel University, Faculty of Sciences, Division of Biochemistry, Chemistry Department, Damietta University, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Department of Biochemistry, Microbiology and Immunology, University of Ottawa [Ottawa], Inflammation Division, The Walter and Eliza Hall Institute of Medical Research (WEHI), Department of Medical Biology, Hacettepe University Faculty of Medicine, Partner site Munich, German Centre for Infection Research (DZIF), Research Unit Gene Vectors, Helmholtz-Zentrum München (HZM), Department of Molecular and Comparative Pathobiology and Department of Neurology, Johns Hopkins University School of Medicine, Fédération de Médecine Translationelle de Strasbourg (FMTS), LabEx Medalis, Université de Strasbourg (UNISTRA), U1109, MN3T, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Institute of Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], German Center for Neurodegenerative Diseases, Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research Institute, Department of Genetics, Cell- and Immunobiology, Semmelweis University, School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Population Health and Immunity Division, Laboratory of Lipid Metabolism and Cancer, Department of Oncology, LKI - Leuven Cancer Institute, Faculty of Biological and Environmental Sciences [Helsinki], University of Helsinki, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, National Cancer Center, Fund for Scientific Spearheads of the Ghent University Hospital, Concerted Research Actions from Ghent University, Stichting tegen Kanker, Kom Op Tegen Kanker, H2020/COST ME-HaD, Fund for Scientific Research Flanders (FWO), Krediet aan Navorsers from FWO, Universiteit Gent = Ghent University (UGENT), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Helmholtz Zentrum München = German Research Center for Environmental Health, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Van Deun J., Mestdagh P., Agostinis P., Akay O., Anand S., Anckaert J., Martinez Z.A., Baetens T., Beghein E., Bertier L., Berx G., Boere J., Boukouris S., Bremer M., Buschmann D., Byrd J.B., Casert C., Cheng L., Cmoch A., Daveloose D., De Smedt E., Demirsoy S., Depoorter V., Dhondt B., Driedonks T.A.P., Dudek A., Elsharawy A., Floris I., Foers A.D., Gartner K., Garg A.D., Geeurickx E., Gettemans J., Ghazavi F., Giebel B., Kormelink T.G., Hancock G., Helsmoortel H., Hill A.F., Hyenne V., Kalra H., Kim D., Kowal J., Kraemer S., Leidinger P., Leonelli C., Liang Y., Lippens L., Liu S., Lo Cicero A., Martin S., Mathivanan S., Mathiyalagan P., Matusek T., Milani G., Monguio-Tortajada M., Mus L.M., Muth D.C., Nemeth A., Nolte-'T Hoen E.N.M., O'Driscoll L., Palmulli R., Pfaffl M.W., Primdal-Bengtson B., Romano E., Rousseau Q., Sahoo S., Sampaio N., Samuel M., Scicluna B., Soen B., Steels A., Swinnen J.V., Takatalo M., Thaminy S., Thery C., Tulkens J., Van Audenhove I., Van Der Grein S., Van Goethem A., Van Herwijnen M.J., Van Niel G., Van Roy N., Van Vliet A.R., Vandamme N., Vanhauwaert S., Vergauwen G., Verweij F., Wallaert A., Wauben M., Witwer K.W., Zonneveld M.I., De Wever O., Vandesompele J., Hendrix A., Ghent University [Belgium] (UGENT), Université Catholique de Louvain, Technical University of Munich (TUM), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), University of Ottawa [Ottawa] (uOttawa), Walter and Eliza Hall Institute of Medical Research (WEHI), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PSL Research University (PSL), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)

Subjects
0301 basic medicine, minimum information, blood-plasma, physiology [Extracellular Vesicles], Biomedical Research, Internationality, Computer science, phenotype, [SDV]Life Sciences [q-bio], Medizin, exosomes, Crowdsourcing, Bioinformatics, Biochemistry, 03 medical and health sciences, Extracellular Vesicles, ultracentrifugation, Biological property, cancer, ddc:610, resolution flow-cytometry, Molecular Biology, subpopulations, business.industry, biological-properties, Cell Biology, Extracellular vesicle, Data science, Databases, Bibliographic, Replication (computing), 030104 developmental biology, cells, business, Biotechnology
Abstract

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.

Published
2017
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10. Acoustic neuroma risk in relation to mobile telephone use: results of the INTERPHONE international case-control study

Author

L. Montestruq, Gabriele Berg-Beckhoff, Anthony J. Swerdlow, N Yamaguchi, Maria Blettner, Joachim Schüz, Neil Pearce, Louise Nadon, Anna Lahkola, C. Johansen, Daniel Krewski, Bruce K. Armstrong, Anne-Sophie Evrard, Tore Tynes, Monika Moissonnier, J Siemiatycki, Ivano Iavarone, Anders Ahlbom, Avital Jarus-Hakak, Martine Vrijheid, M. Bernard, K. G. Blaasaas, Alistair Woodward, S. J. Hepworth, Salminen T, Isabelle Deltour, J Brown, Elisabeth Cardis, Martine Hours, Angela Chetrit, Päivi Kurttio, Patricia A. McKinney, Sigrid Lönn, Maria Feychting, Lars Klaeboe, Siegal Sadetzki, Brigitte Schlehofer, Helle Collatz Christensen, Toru Takebayashi, Interphone Study Grp, Susanna Lagorio, Anssi Auvinen, G.G. Giles, Angus Cook, M. M McBride, Minouk J. Schoemaker, Marie-Élise Parent, Kenneth Muir, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), International Agency for Cancer Research (IACR), IMIM-Hospital del Mar, Generalitat de Catalunya, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Sydney Cancer Centre and School of Public Health, The University of Sydney, Cancer Epidemiology Centre, The Cancer Council Victoria, School of Public Health and Hospital Research Center, Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], Cancer Research Centre, BC Cancer Agency (BCCRC), Danish Cancer Society, Institute of Cancer Epidemiology, Radiation and Nuclear Safety Authority [Helsinki] (STUK), Département Transport, Santé, Sécurité (IFSTTAR/TS2), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Lyon, Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg - Universität Mainz (JGU), Department of Epidemiology and International Public Health, Universität Bielefeld = Bielefeld University-Faculty of Public Health, Unit of Environmental Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, National Centre for Epidemiology Surveillance and Health Promotion, National Institute of Health, Department of Preventive Medicine and Public Health, University School of Medicine, Department of Public Health, University of Otago [Dunedin, Nouvelle-Zélande], Norwegian Radiation Protection Authority, The Cancer Registry of Norway, Norwegian Armed Forces Medical Services, The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], University of Leeds, The Health Science Research Institute, University of Warwick [Coventry], Institute of Cancer Research, Institute of cancer research, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, This work was supported by funding from the European Fifth Framework Program, ‘Quality of Life and Management of Living Resources’ (contract QLK4-CT-1999901563) and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers’ Forum and GSM Association. Provision of funds to the INTERPHONE study investigators via the UICC was governed by agreements that guaranteed INTERPHONE's complete scientific independence. The terms of these agreements are publicly available at http://www.iarc.fr/en/research-groups/RAD/RCAd.html.The Australian centre was supported by the Australian National Health and Medical Research Council (EME Grant 219129) with funds originally derived from mobile phone service licence fees, Julianne Brown was partly supported by an Australian Postgraduate Award. Cancer Council NSW and Cancer Council Victoria provided most of the infrastructure for the project in Australia.The Canadian centres in Ottawa/Vancouver were supported by a university–industry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR university–industry partnerships program also includes provisions that ensure complete scientific independence of the investigators. D. Krewski is the Natural Sciences and Engineering Research Council of Canada Chair in Risk Science at the University of Ottawa.The Canada – Montreal study was primarily funded by a grant from the Canadian Institutes of Health Research (project 15 MOP-42525). Additionally, Dr Siemiatycki's research team was partly funded by the Canada Research Chair programme and by the Guzzo-CRS Chair in Environment and Cancer. Dr Parent had a salary award from the Fonds de la recherche en santé du Québec.Additional funding for the study in France was provided by l’Association pour la Recherche sur le Cancer (ARC) [Contrat No. 5142] and three network operators (Orange, SFR, Bouygues Télécom). The funds provided by the operators represented 5% of the total cost of the French study and were governed by contracts guaranteeing the complete scientific independence of the investigators.The Finnish Interphone study received additional national funding from Emil Aaltonen Foundation and Academy of Finland (Grant No. 80921).The German Interphone study received additional national funding from the 'Deutsches Mobilfunkforschungsprogramm [German Mobile Phone Research Program]' of the German Federal Ministry of Environment, Nuclear Safety, and Nature Protection, the Ministry of Environment and Traffic of the state of Baden-Württemberg, the Ministry of Environment of the state of North Rhine-Westphalia, and the MAIFOR Programme of the University of Mainz.The Japanese Interphone study was fully funded by the Ministry of Internal Affairs and Communications of Japan.Funding in New Zealand for this project was provided by the Health Research Council of New Zealand, the Cancer Society of New Zealand, the Wellington Medical Research Foundation, the Hawke's Bay Medical Research Foundation and the Waikato Medical Research Foundation.The Swedish centre was additionally supported by the Swedish Research Council and the Swedish Cancer Society.The UK North study received additional funding from the Health and Safety Executive, the Department of Health, the Mobile Telecommunications, Health and Research (MTHR) program, and the Scottish Executive. The University of Leeds received some financial support on behalf of the 4 centres of the ‘UK North Study’ from the UK Network Operators (O2, Orange, T-Mobile, Vodafone, ‘3’) under legal signed contractual agreements which guaranteed complete independence for the scientific investigators.The Southeast England Centre wishes to acknowledge additional funding from the Mobile Telecommunications, Health and Research (MTHR) programme. The views expressed in this publication are those of the authors and not necessarily of the funders., and The INTERPHONE Study Group

Subjects
Male, Cancer Research, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, Epidemiology, MESH: Electromagnetic Fields, Decile, MESH: Glioma, 0302 clinical medicine, Risk Factors, Phone, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Meningeal Neoplasms, Odds Ratio, Medicine, Mobile phones, MESH: Middle Aged, Brain Neoplasms, Brain tumour, Glioma, Neuroma, Acoustic, MESH: Follow-Up Studies, Middle Aged, Prognosis, MESH: Case-Control Studies, 3. Good health, Survival Rate, Oncology, Reporting bias, 030220 oncology & carcinogenesis, Censoring (clinical trials), MESH: Brain Neoplasms, Female, Adult, MESH: Survival Rate, Acoustic neuroma, Radiofrequency electromagnetic fields, MESH: Prognosis, MESH: International Agencies, 03 medical and health sciences, Electromagnetic Fields, Vestibular schwannoma, Humans, MESH: Humans, business.industry, International Agencies, MESH: Adult, Odds ratio, medicine.disease, MESH: Meningeal Neoplasms, Confidence interval, MESH: Male, MESH: Odds Ratio, MESH: Cellular Phone, Mobile phone, Case-Control Studies, business, MESH: Female, Cell Phone, 030217 neurology & neurosurgery, Follow-Up Studies, Demography, MESH: Neuroma, Acoustic
Abstract

Background: The rapid increase in mobile telephone use has generated concern about possible health risks of radiofrequency electromagnetic fields from these devices. Methods: A case-control study of 1105 patients with newly diagnosed acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13 countries using a common protocol. Past mobile phone use was assessed by personal interview. In the primary analysis, exposure time was censored at one year before the reference date (date of diagnosis for cases and date of diagnosis of the matched case for controls); analyses censoring exposure at five years before the reference date were also done to allow for a possible longer latent period. Results: The odds ratio (OR) of acoustic neuroma with ever having been a regular mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for >= 10 years after first regular mobile phone use was 0.76 (0.52-1.11). There was no trend of increasing ORs with increasing cumulative call time or cumulative number of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of cumulative call time. In the 10th decile (>= 1640 h) of cumulative call time, the OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use in those with >= 1640 h of accumulated mobile phone use. With censoring at 5 years before the reference date the OR for >= 10 years after first regular mobile phone use was 0.83 (0.58-1.19) and for >= 1640 h of cumulative call time it was 2.79(1.51-5.16). but again with no trend in the lower nine deciles and with the lowest OR in the 9th decile. In general, ORs were not greater in subjects who reported usual phone use on the same side of the head as their tumour than in those who reported it on the opposite side, but it was greater in those in the 10th decile of cumulative hours of use. Conclusions: There was no increase in risk of acoustic neuroma with ever regular use of a mobile phone or for users who began regular use 10 years or more before the reference date. Elevated odds ratios observed at the highest level of cumulative call time could be due to chance, reporting bias or a causal effect. As acoustic neuroma is usually a slowly growing tumour, the interval between introduction of mobile phones and occurrence of the tumour might have been too short to observe an effect, if there is one. (C) 2011 Elsevier Ltd. All rights reserved.

Published
2011
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11. Acceptability and feasibility of FAMS-T1D mHealth intervention to optimize self- and social regulation for emerging adults with type 1 diabetes.

Author

Mayberry LS, Wiebe DJ, Parks M, Campbell MS, Beam AB, and Berg CA

Abstract

Background: Among emerging adults with type 1 diabetes (T1D), self-regulation and social regulation skills can help avoid high A1c and diabetes distress. FAMS (Family/friend Activation to Motivate Self-care) is mobile phone-delivered intervention that supports development of these skills and is efficacious among adults with type 2 diabetes. However, the acceptability and feasibility of the FAMS intervention among emerging adults with T1D are unknown., Methods: Therefore, we adapted FAMS for in a new disease context and developmental stage and then conducted a 3-month mixed-methods pre-post pilot study. Participants were emerging adults with T1D and a friend/family member enrolled as a support person (optional). Feasibility/acceptability outcomes and associated progression thresholds were recruitment (≥ 70% eligible emerging adults), retention (≥ 85%), intervention engagement (≥ 70%), and satisfaction (≥ 70%). We also collected qualitative feedback to determine if the intervention addressed relevant needs and explored changes in outcomes of interest (family/friend involvement, self-efficacy, self-management, distress, A1c)., Results: Recruitment rates indicate recruitment of emerging adults with T1D (n = 30) and their support persons (n = 20) is feasible - 79% of emerging adults who screened as eligible enrolled and 70% of enrolled emerging adults invited a support person. Emerging adults completed 98% of coaching sessions, and response rates to automated text messages were median 85% IQR [68%, 90%]. Changes in selected measures for outcomes of interest were in expected directions suggesting sensitivity to changes occasioned by the intervention in a future evaluative trial. Emerging adults said FAMS-T1D helped with setting realistic goals, motivated them to prioritize diabetes goals, and increased support, indicating acceptability of the intervention in this new disease and developmental context., Conclusions: Findings suggest potential for FAMS-T1D to engage emerging adults and their support persons and feasibility for an evaluative trial examining effects on self-regulation (self-efficacy, self-management), social regulation (family/friend involvement), and outcomes (diabetes distress, A1c)., Trial Registration: We did not register this study on ClinicalTrials.gov because the purpose of the study was to assess the feasibility and acceptability of the intervention and study procedures and measures in preparation for a future trial. The purpose of that future trial will be to evaluate the effect of the intervention on health-related biomedical and behavioral outcomes, and that trial will be registered accordingly., (© 2024. The Author(s).)

Published
2024
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12. Substance Use Among Asian American Adults in 2016-2020: A Difference-in-Difference Analysis of a National Survey on Drug Use and Health Data.

Author

Yan Y, Yoshihama M, Hong JS, and Jia F

Subjects
Adult, Humans, Asian, COVID-19 epidemiology, Pandemics, United States epidemiology, White, Substance-Related Disorders epidemiology
Abstract

Objectives. To compare substance use among Asian American adults in 2020, when anti-Asian violence increased, with substance use among the same group during the previous 4 years and compare this with that of non-Hispanic Whites. Methods. Using data from the National Survey on Drug Use and Health, 2016 to 2020, we investigated changes in substance use among Asian Americans compared with non-Hispanic Whites before and during the COVID-19 pandemic. We performed difference-in-difference analyses to estimate adjusted changes in past-month substance use in the 2 groups. Results. The incidence rate ratio (IRR) among Asian Americans' past-month alcohol use, cocaine use, and tranquilizer misuse in 2020 versus in 2016 to 2019 was 1.3 times, 3.0 times, and 17.2 times, respectively, the same IRR among Whites. Conclusions. The significant increase in misuse of several substances among Asian Americans relative to Whites in 2020 calls for careful assessment, identification, and treatment of this understudied population group. Public Health Implications. Besides increasing Asian substance users' access to socioculturally responsive treatment programs, policy and resources should be focused on multilevel violence prevention efforts such as antiracial discrimination public education programs. ( Am J Public Health. 2023;113(6):671-679. https://doi.org/10.2105/AJPH.2023.307256).

Published
2023
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13. Intravital fluorescence microscopy with negative contrast.

Author

Wu JW, Jung Y, Yeh SA, Seo Y, Runnels JM, Burns CS, Mizoguchi T, Ito K, Spencer JA, and Lin CP

Subjects
Animals, Automation, Bone Marrow diagnostic imaging, Female, Fluorescent Dyes chemistry, Lymph Nodes diagnostic imaging, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Regional Blood Flow, Time Factors, Mice, Contrast Media chemistry, Intravital Microscopy
Abstract

Advances in intravital microscopy (IVM) have enabled the studies of cellular organization and dynamics in the native microenvironment of intact organisms with minimal perturbation. The abilities to track specific cell populations and monitor their interactions have opened up new horizons for visualizing cell biology in vivo, yet the success of standard fluorescence cell labeling approaches for IVM comes with a "dark side" in that unlabeled cells are invisible, leaving labeled cells or structures to appear isolated in space, devoid of their surroundings and lacking proper biological context. Here we describe a novel method for "filling in the void" by harnessing the ubiquity of extracellular (interstitial) fluid and its ease of fluorescence labelling by commonly used vascular and lymphatic tracers. We show that during routine labeling of the vasculature and lymphatics for IVM, commonly used fluorescent tracers readily perfuse the interstitial spaces of the bone marrow (BM) and the lymph node (LN), outlining the unlabeled cells and forming negative contrast images that complement standard (positive) cell labeling approaches. The method is simple yet powerful, offering a comprehensive view of the cellular landscape such as cell density and spatial distribution, as well as dynamic processes such as cell motility and transmigration across the vascular endothelium. The extracellular localization of the dye and the interstitial flow provide favorable conditions for prolonged Intravital time lapse imaging with minimal toxicity and photobleaching., Competing Interests: The authors have declared that no competing interests exist.

Published
2021
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14. Two-Photon Phosphorescence Lifetime Microscopy.

Author

Abbasizadeh N and Spencer JA

Subjects
Humans, Microscopy, Fluorescence, Oxygen, Photons
Abstract

Two-photon Phosphorescence Lifetime Microscopy (2PLM) is an emerging nonlinear optical technique that has great potential to improve our understanding of the basic biology underlying human health and disease. Although analogous to 2-photon Fluorescence Lifetime Imaging Microscopy (2P-FLIM), the contrast in 2PLM is fundamentally different from various intensity-based forms of imaging since it is based on the lifetime of an excited state and can be regarded as a "functional imaging" technique. 2PLM signal originates from the deactivation of the excited triplet state (phosphorescence) [1, 2]. Typically, this triplet state is a much longer-lived excited state than the singlet excited state resulting in phosphorescence emission times of microseconds to milliseconds at room temperature as opposed to nanoseconds for fluorescence emission [3]. The long-lived nature of the triplet state makes it highly sensitive to quenching molecules in the surrounding environment such as biomolecular oxygen (O 2 ). Therefore, 2PLM can provide not only information on the distribution pattern of the probe in the sample (via intensity) but also determine the local oxygen tension (via phosphorescence lifetime quenching) [1]. The ability to create three-dimensional optical sections in the plane of focus within a thick biological specimen while maintaining relatively low phototoxicity due to the use of near-infrared wavelengths for two-photon excitation gives 2PLM powerful advantages over other techniques for longitudinal imaging and monitoring of oxygen within living organisms [4]. In this chapter, we will provide background on the development of 2PLM, discuss the most common oxygen sensing measurement methods and concepts, and explain the general principles and optical configuration of a 2PLM system. We also discuss the key characteristics and strategies for improvement of the technique. Finally, we will present an overview of the current primary scientific literature of how 2PLM has been used for oxygen sensing in biological applications and how this technique is improving our understanding of the basic biology underlying several areas of human health.

Published
2021
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