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Comprehensive characterization of mesenchymal stromal cells from patients with Fanconi anaemia
Author(s) -
Mantelli Melissa,
Avanzini Maria Antonia,
Rosti Vittorio,
Ingo Daniela M.,
Conforti Antonella,
Novara Francesca,
Arrigo Giulia,
Boni Marina,
Zappatore Rita,
Lenta Elisa,
Moretta Antonia,
Acquafredda Gloria,
Silvestri Annalisa,
Cirillo Valentina,
Cicchetti Elisa,
Algeri Mattia,
Strocchio Luisa,
Vinti Luciana,
Starc Nadia,
Biagini Simone,
Sirleto Pietro,
Bernasconi Paolo,
Zuffardi Orsetta,
Maserati Emanuela,
Maccario Rita,
Zecca Marco,
Locatelli Franco,
Bernardo Maria Ester
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13504
Subject(s) - mesenchymal stem cell , immunophenotyping , haematopoiesis , biology , bone marrow , cancer research , stem cell , stromal cell , immunology , fanconi anemia , microbiology and biotechnology , genetics , dna repair , antigen , gene
Summary 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 ( MSC s) 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 ‐ MSC s were analysed and compared with those of MSC s expanded from 15 age‐matched healthy donors ( HD ‐ MSC s). FA ‐ MSC s were genetically characterized through conventional karyotyping, diepoxybutane‐test and array‐comparative genomic hybridization. FA ‐ MSC s 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 ‐ MSC s and HD ‐ MSC s. CFU ‐F ability and proliferative capacity of FA ‐ MSC s isolated after HSCT were significantly lower than those of HD ‐ MSC s. FA ‐ MSC s reached senescence significantly earlier than HD ‐ MSC s and showed spontaneous chromosome fragility. Our findings indicate that FA ‐ MSC s 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.