In:
British Journal of Haematology, Wiley, Vol. 170, No. 6 ( 2015-09), p. 826-836
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 ( 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.
Type of Medium:
Online Resource
ISSN:
0007-1048
,
1365-2141
DOI:
10.1111/bjh.2015.170.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
1475751-5