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Artigues-près-Bordeaux, France

Guitart A.V.,University of Bordeaux 1 | Guitart A.V.,French National Center for Scientific Research | Debeissat C.,University of Bordeaux 1 | Debeissat C.,French National Center for Scientific Research | And 10 more authors.
Cell Death and Differentiation | Year: 2011

Oxygen (O2) concentrations in bone marrow vary from 4% in capillaries to 0.1% in subendosteum, in which hematopoietic stem cells reside in specific niches. Culture at low O2 concentrations (3, 1 and 0.1%) influences hematopoietic stem and progenitor cells survival, proliferation and differentiation, depending on their level of differentiation. Culture of human CD34 cells at low O2 concentrations (O2 3%) maintains stem cell engraftment potential better than at 20% O2 (NOD/Scid xenograft model). In contrast, progenitors disappear from cultures at/or 1% O2 concentrations. A very low O2 concentration (0.1%) induces CD34 quiescence in G 0. The exploration of molecules and mechanisms involved in hematopoietic stem and progenitor cells quiescence and differentiation related to low O2 concentrations is unfeasible with primary CD34 cells. Therefore, we performed it using murine hematopoietic nonleukemic factor-dependent cell Paterson (FDCP)-Mix progenitor cell line. The culture of the FDCP-Mix line at 0.1% O2 induced in parallel G 0 quiescence and granulo-monocytic differentiation of most cells, whereas a minority of undifferentiated self-renewing cells remained in active cell cycle. Hypoxia also induced hypophosphorylation of pRb and increased the expression of p27 KIP1, the two proteins that have a major role in the control of G 0 and G 1 to S-phase transition. © 2011 Macmillan Publishers Limited All rights reserved.

Bijou F.,Etablissement Francais du Sang Aquitaine Limousin | Boiron J.-M.,Etablissement Francais du Sang Aquitaine Limousin | Boiron J.-M.,University of Bordeaux 1
Hematologie | Year: 2010

These last decades had been marked by increased use of hematopoietic stem cell transplantation procedures as well as many improvements in transfusion medicine. This article is a review of common guidelines used in the context of transfusions requirements management for potential candidates assigned to autologous or allogeneic transplantations. Transfusion support does lead hospitals and transfusion center physicians to consider different parameters related to immunosuppression and alloimmunization degree of patients in autologous settings and moreover, patients and/or donor ABO phenotype incompatibility, source of stem cells, patients and/or donor cytomegalovirus status in allogeneic ones before during and even after transplantation. Increased use of transfusions is common in this population of patients and delay of transfusion requirements before transplantation is another paramount challenge in prevention of alloimmunization risk. Indeed we will discuss indispensable and validated criteria of specific transformation and specialized qualification of blood or cellular therapy components before its administration in the aim to optimize patients outcome. The latter could be worsened by Donor/Recipient ABO incompatibility, inadequate prevention of cytomegalovirus risk.

Gallian P.,Etablissement francais du sang Alpes Mediterranee | Gallian P.,Aix - Marseille University | Piquet Y.,Etablissement Francais du Sang Aquitaine Limousin | Assal A.,Etablissement Francais du Sang Aquitaine Limousin | And 7 more authors.
Transfusion Clinique et Biologique | Year: 2014

Hepatitis E virus (HEV) is a non-enveloped RNA virus transmitted by the fecal-oral route. Autochthonous hepatitis E occurring in developed countries is caused by genotypes 3 and 4 and is a zoonotic infection. Humans are infected mostly after ingestion of undercooked meat from infected animals. Most HEV 3 and 4 infections are clinically inapparent. However, genotype 3 (HEV 3) can lead to chronic hepatitis in immuno-compromised patients such as organ-transplant recipients and patients with haematological malignancies. In Europe, HEV 3 is implicated in transfusion-transmitted HEV infection. In France, as observed in several European countries, prevalence of HEV RNA and specific IgG antibodies are high indicating that viral circulation is important. The systematic HEV NAT screening of blood donations used for preparation of solvent detergent plasma indicate that 1 to 2218 donation is infected by HEV RNA. The need or implementation's impacts of safety measures to prevent HEV transmission by blood transfusion are under reflexion by French's health authorities. The HEV NAT screening is the only available tool of prevention. Alternative strategies are under investigation including individual or mini pool NAT testing all or part of blood donations. © 2014 Elsevier Masson SAS.

Godfrey A.L.,University of Cambridge | Chen E.,University of Cambridge | Pagano F.,University of Cambridge | Ortmann C.A.,University of Cambridge | And 15 more authors.
Blood | Year: 2012

Subclones homozygous for JAK2V617F are more common in polycythemia vera (PV) than essential thrombocythemia (ET), but their prevalence and significance remain unclear. The JAK2 mutation status of 6495 BFU-E, grown in low erythropoietin conditions, was determined in 77 patients with PV or ET. Homozygous-mutant colonies were common in patients with JAK2V617F-positive PV and were surprisingly prevalent in JAK2V617F-positive ET and JAK2 exon 12-mutated PV. Using microsatellite PCR to map loss-of-heterozygosity breakpoints within individual colonies, we demonstrate that recurrent acquisition of JAK2V617F homozygosity occurs frequently in both PV and ET. PV was distinguished from ET by expansion of a dominant homozygous subclone, the selective advantage of which is likely to reflect additional genetic or epigenetic lesions. Our results suggest a model in which development of a dominant JAK2V617F-homzygous subclone drives erythrocytosis in many PV patients, with alternative mechanisms operating in those with small or undetectable homozygous-mutant clones. © 2012 by The American Society of Hematology.

Vlaski-Lafarge M.,Etablissement Francais du Sang Aquitaine Limousin | Vlaski-Lafarge M.,University of Bordeaux Segalen | Ivanovic Z.,Etablissement Francais du Sang Aquitaine Limousin | Ivanovic Z.,University of Bordeaux Segalen
Journal of Cell Science | Year: 2015

Many studies have provided evidence for the crucial role of the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the regulation of differentiation and/or self-renewal, and the balance between quiescence and proliferation of hematopoietic stem cells (HSCs). Several metabolic regulators have been implicated in the maintenance of HSC redox homeostasis; however, the mechanisms that are regulated by ROS and RNS, as well as their downstream signaling are still elusive. This is partially owing to a lack of suitable methods that allow unequivocal and specific detection of ROS and RNS. In this Opinion, we first discuss the limitations of the commonly used techniques for detection of ROS and RNS, and the problem of heterogeneity of the cell population used in redox studies, which, together, can result in inaccurate conclusions regarding the redox biology of HSCs. We then propose approaches that are based on single-cell analysis followed by a functional test to examine ROS and RNS levels specifically in HSCs, as well as methods that might be used in vivo to overcome these drawbacks, and provide a better understanding of ROS and RNS function in stem cells. © 2015.

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