title: Characterization of bone marrow mesenchymal stromal cells in aplastic anaemia.
abstract: In aplastic anaemia (AA), haemopoietic activity is significantly reduced and generally attributed to failure of haemopoietic stem cells (HSC) within the bone marrow (BM). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the BM microenvironment, including mesenchymal stromal cells (MSC). MSC involvement in the functional restriction of HSC in AA is largely unknown and therefore, the physical and functional properties of AA MSC were studied in vitro. MSC were characterized by their phenotype and ability to form adherent stromal layers. The functional properties of AA MSC were assessed through proliferative, clonogenic and cross-over culture assays. Results indicate that although AA MSC presented typical morphology and distinctive mesenchymal markers, stromal formation was reduced, with 50% of BM samples failing to produce adherent layers. Furthermore, their proliferative and clonogenic capacity was markedly decreased (P = 0·03 and P = 0·04 respectively) and the ability to sustain haemopoiesis was significantly reduced, as assessed by total cell proliferation (P = 0·032 and P = 0·019 at Week 5 and 6, respectively) and clonogenic potential of HSC (P = 0·02 at Week 6). It was concluded that the biological characteristics of AA MSC are different from those of control MSC and their in vitro haemopoiesis-supporting ability is significantly reduced.
authors.affiliation: Department of Infection and Immunity, St George's University of London, London, UK.|Department of Life Sciences, Kingston University, Kingston upon Thames, UK.
authors.forename: Edita
authors.initials: E
authors.lastname: Hamzic
authors.affiliation: Department of Life Sciences, Kingston University, Kingston upon Thames, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Whiting
authors.affiliation: Department of Infection and Immunity, St George's University of London, London, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Gordon Smith
authors.affiliation: Department of Infection and Immunity, St George's University of London, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Pettengell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002452:Cell Count; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: aplastic anaemia; bone marrow culture; haematopoiesis; haematopoietic stem cells; mesenchymal cells