Mesenchymal cells generated from patients with myelodysplastic syndromes are devoid of chromosomal clonal markers and support short- and long-term hematopoiesis in vitro.
Myelodysplastic syndromes (MDS) are clonal malignant stem cell disorders characterized by inefficient hematopoiesis. The role of the marrow microenvironment in the pathogenesis of the disease has been controversial and no study has been performed so far to characterize mesenchymal cells (MC) from MDS patients and to analyse their ability to support hematopoiesis. To this end, we have isolated and characterized MC at diagnostic marrow samples (n=12) and have purified their CD34+CD38- and CD34+CD38+ counterparts (n=7) before using MC as a short- and long-term hematopoietic support. We show that MC can be readily isolated from MDS marrow and exhibit a major expansion potential as well as an intact osteoblastic differentiation ability. They do not harbor the abnormal marker identified by FISH in the hematopoietic cells and they stimulate the growth of autologous clonogenic cells. Conversely, highly purified stem cells and their cytokine-expanded progeny harbor the clonal marker with variable frequencies, and both normal and abnormal long-term culture-initiating cell-derived progeny can be effectively supported by autologous MC. Thus, we demonstrate that MDS marrow is an abundant source of MC appearing both cytogenetically and functionally noninvolved by the malignant process and able to support hematopoiesis, suggesting their possible usefulness in future cell therapy approaches.
Soenen-Cornu
Valérie
V
Inserm U524, CHU Lille, France.
Tourino
Cristina
C
Bonnet
Marie-Laure
ML
Guillier
Martine
M
Flamant
Stéphane
S
Kotb
Rami
R
Bernheim
Alain
A
Bourhis
Jean-Henri
JH
Preudhomme
Claude
C
Fenaux
Pierre
P
Turhan
Ali G
AG
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000293:Adolescent; D000368:Aged; D015703:Antigens, CD; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008562:Membrane Glycoproteins; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000503:physiopathology*
D015703:Antigens, CD; D016207:Cytokines; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1