title: Comprehensive characterization of mesenchymal stromal cells from patients with Fanconi anaemia.
abstract: Fanconi anaemia (FA) is an inherited disorder characterized by pancytopenia, congenital malformations and a predisposition to develop malignancies. Alterations in the haematopoietic microenvironment of FA patients have been reported, but little is known regarding the components of their bone marrow (BM) stroma. We characterized mesenchymal stromal cells (MSCs) isolated from BM of 18 FA patients both before and after allogeneic haematopoietic stem cell transplantation (HSCT). Morphology, fibroblast colony-forming unit (CFU-F) ability, proliferative capacity, immunophenotype, differentiation potential, ability to support long-term haematopoiesis and immunomodulatory properties of FA-MSCs were analysed and compared with those of MSCs expanded from 15 age-matched healthy donors (HD-MSCs). FA-MSCs were genetically characterized through conventional karyotyping, diepoxybutane-test and array-comparative genomic hybridization. FA-MSCs generated before and after HSCT were compared. Morphology, immunophenotype, differentiation potential, ability in vitro to inhibit mitogen-induced T-cell proliferation and to support long-term haematopoiesis did not differ between FA-MSCs and HD-MSCs. CFU-F ability and proliferative capacity of FA-MSCs isolated after HSCT were significantly lower than those of HD-MSCs. FA-MSCs reached senescence significantly earlier than HD-MSCs and showed spontaneous chromosome fragility. Our findings indicate that FA-MSCs are defective in their ability to survive in vitro and display spontaneous chromosome breakages; whether these defects are involved in pathophysiology of BM failure syndromes deserves further investigation.
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Mantelli
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Avanzini
authors.affiliation: Centre for the Study and Treatment of Myelofibrosis, Research Laboratories of Biotechnology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Ingo
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Conforti
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Novara
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Arrigo
authors.affiliation: Laboratory of Cytogenetic and Molecular Onco-haematology, Haematology Department, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Boni
authors.affiliation: Laboratory of Cytogenetic and Molecular Onco-haematology, Haematology Department, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Zappatore
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lenta
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Acquafredda
authors.affiliation: Clinical Epidemiology and Biometrics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: de Silvestri
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirillo
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cicchetti
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.|University of Pavia, Pavia, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Algeri
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Strocchio
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Vinti
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Starc
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Biagini
authors.affiliation: Cytogenetics and Molecular Genetics Unit, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Sirleto
authors.affiliation: Laboratory of Cytogenetic and Molecular Onco-haematology, Haematology Department, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernasconi
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.affiliation: Clinical and Experimental Medicine Department, University of Insubria, Varese, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maserati
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.|University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department of Paediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005260:Female; D005838:Genotype; D006410:Hematopoiesis; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D059785:Karyotype; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018895:Microsatellite Repeats / Q000235:genetics
chemical_list: D000954:Antigens, Surface
keywords: Fanconi anaemia; bone marrow niche; genetic stability; immunomodulatory properties; mesenchymal stromal cells