Front. Oncol., 12 May 2020

Normal Hematopoetic Stem and Progenitor Cells Can Exhibit Metabolic Flexibility Similar to Cancer Cells

Marija Vlaski-Lafarge et al.
It is known that cancer stem cells (CSCs) with the largest proliferative capacity survive the anoxic and/or ischemic conditions present inside tumorous tissue. In this study we test whether normal stem cells can survive under the same conditions due to cancer cell-like metabolic adaptations. We cultivated a CD34+ population with a majority of hematopoietic progenitors, and a CD34+CD38lowCD133+CD90+CD45RA− population, highly enriched in hematopoietic stem cells (HSCs), under anoxic, anoxic/aglycemic (“ischemia-like”), or physiological conditions (3% O2). Results showed, despite a reduction in total cell fold expansion proportionate to the decrease in O2 concentration; CD34+ cells, aldehyde dehydrogenase-expressing primitive cells, and committed progenitors expanded, even in anoxia. Interestingly, under ischemia-like conditions, stem and CD34+ cell populations are maintained at day-0 level. Cell-cycle analysis further revealed an accumulation of cells in the G0/G1 phase in anoxia or anoxia/aglycemia, with a fraction of cells (~40%) actively cycling (SG2M phases). Also stem cell analysis showed that in these conditions a long-term Scid Repopulating activity was equal to that found with 3% O2. In addition stem cells with the highest proliferative capacity were maintained in anoxia/aglycemia and in anoxia. The estimated ATP profile, active mitochondrial content, and succinate accumulation are indicative of anaerobic mitochondrial respiration in both HSCs and CD34+ progenitors under ischemia-like conditions. We demonstrate here that primitive hematopoietic cells show similar metabolic flexibility to CSCs, allowing them to survive a lack of O2 and O2/glucose. Our study reveals that this feature is not the consequence of malignant transformation, but an attribute of stemness.

A-S Espadinha et al, Oncotarget 2017

A tyrosine kinase-STAT5-miR21-PDCD4 regulatory axis in chronic and acute myeloid leukemia cells

ABSTRACT
MicroRNAs (miRNAs) are regulators of several key patho-physiological processes, including cell cycle and apoptosis. Using microarray-based miRNA profiling in K562 cells, a model of chronic myeloid leukemia (CML), we found that the oncoprotein BCR-ABL1 regulates the expression of miR-21, an “onco-microRNA”, found to be overexpressed in several cancers. This effect relies on the presence of two STAT binding sites on the promoter of miR-21, and on the phosphorylation status of STAT5, a transcription factor activated by the kinase activity of BCR-ABL1. Mir-21 regulates the expression of PDCD4 (programmed cell death protein 4), a tumor suppressor identified through a proteomics approach. The phosphoSTAT5 — miR-21 — PDCD4 pathway was active in CML primary CD34+ cells, but also in acute myeloid leukemia (AML) models like MV4.11 and MOLM13, where the constitutively active tyrosine kinase FLT3-ITD plays a similar role to BCR-ABL1 in the K562 cell line.

(STEM ALPHA.A #5510)

C.S. Jackson et al. / Stem Cell Research

Targeting the aryl hydrocarbon receptor nuclear translocator complexwith DMOG and Stemregenin 1 improves primitive hematopoietic stemcell expansion

Culture conditions used for the expansion of hematopoietic stem and progenitor cells (HSCs and HPCs, collective-ly HSPCs) should ideally favor the self renewal of long-term HSCs. At 20% O2, the synthesis of HIF-1αis balancedby its hydroxylation and proteasomal degradation. This favors HSPC differentiation, but can be prevented by cul-turing CD34+ cord blood cells in the presence of dimethyloxaloylglycine (DMOG). This differentiation may alsobe reduced by culturingthe cells in the presence of Stemregenin 1,anantagonistof the aryl hydrocarbon receptor(AhR). The objective of this study was to investigate how hypoxia, DMOG and Stemregenin 1 might affect the ex-pansion of HSPCs with the aim of identifying optimalconditions for expansionin culture. It was foundthatDMOGdecreased proliferation but was effective in preserving the number of cells in the primitive hematopoietic sub-populationsin vitro. The effect of DMOG was similar to hypoxia, although differences were observed with regardto the side population and CD34+ sub-populations. Stemregenin 1 on the other hand increased the size of theprimitive as well as the other HSC sub-populations. The use of Stemregenin 1 with DMOG increased the propor-tion ofprimitive HSCs to 3.54% comparedto2.61% for Stemregenin 1 alone.Invivoengraftment studiesconfirmedthesefindings and showed that fewer cells (3710) are required for long-term engraftment when HSCs are grownin Stemregenin 1 together with hypoxia than in Stemregenin 1 under conditions of normoxia (13430).

(STEM ALPHA.1D #5112)

A Bourdieu et al, J Cell Physiol 2017

Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.
J Cell Physiol. 2017; (ISSN: 1097-4652)
Bourdieu A; Avalon M; Lapostolle V; Ismail S; Mombled M; Debeissat C; Guérinet M; Duchez P; Chevaleyre J; Vlaski-Lafarge M; Villacreces A; Praloran V; Ivanovic Z; Brunet de la Grange P

Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy.

Product used : STEM LAPHA.1D (#5112)

S Ducassou, T.Journal of Pathology 2017

MYB–GATA1 fusion promotes basophilic leukaemia: involvement of interleukin-33 and nerve growth factor receptors

Abstract
Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloblastic leukaemia. We previously described a recurrent t(X;6)(p11;q23) translocation generating an MYB–GATA1 fusion gene in male infants with ABL. To better understand its role, the chimeric MYB–GATA1 transcription factor was expressed in CD34-positive haematopoietic progenitors, which were transplanted into immunodeficient mice. Cells expressing MYB–GATA1 showed increased expression of markers of immaturity (CD34), of granulocytic lineage (CD33 and CD117), and of basophilic differentiation (CD203c and FcϵRI). UT-7 cells also showed basophilic differentiation after MYB–GATA1 transfection. A transcriptomic study identified nine genes deregulated by both MYB–GATA1 and basophilic differentiation. Induction of three of these genes (CCL23, IL1RL1, and NTRK1) was confirmed in MYB–GATA1-expressing CD34-positive cells by reverse transcription quantitative polymerase chain reaction. Interleukin (IL)-33 and nerve growth factor (NGF), the ligands of IL-1 receptor-like 1 (IL1RL1) and neurotrophic receptor tyrosine kinase 1 (NTRK1), respectively, enhanced the basophilic differentiation of MYB–GATA1-expressing UT-7 cells, thus demonstrating the importance of this pathway in the basophilic differentiation of leukaemic cells and CD34-positive primary cells. Finally, gene reporter assays confirmed that MYB and MYB–GATA1 directly activated NTRK1 and IL1RL1 transcription, leading to basophilic skewing of the blasts. MYB–GATA1 is more efficient than MYB, because of better stability. Our results highlight the role of IL-33 and NGF receptors in the basophilic differentiation of normal and leukaemic cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

(STEM ALPHA.1D #5112)

MethylCelulose Media

Lucia Kubovcacova et al. 2013 Differential effects of hydroxyurea and INC424 on mutant allele burden and myeloproliferative phenotype in a JAK2-V617F polycythemia vera mouse model Blood 2013 121:1188-1199
(STEM ALPHA.I #5110)

Impairing MLL-fusion gene-mediated transformation by dissecting critical interactions with the lens epithelium-derived growth factor (LEDGF/p75) H Mereau et al. Leukemia (2013), 1–9& 2013 Macmillan Publishers Limited All rights reserved 0887-6924/13
(STEM ALPHA.mIE #8008)

Sarah Picaud, David Da Costa, Angeliki Thanasopoulou, et al. 2013 PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains Cancer Res 2013;73:3336-3346.
(STEM ALPHA.1 # 5110)

Philippe Brunet de la Grange et al. 2013 Long-term repopulating hematopoietic stem cells and “side population” in human steady state peripheral blood Stem Cell Research (2013) 11, 625–633
(STEM ALPHA.1D # 5112)

Jean Chevaleyre et al. 2013 Busulfan Administration Flexibility Increases the Applicability of Scid Repopulating Cell Assay in NSG Mouse Model PLOS ONE 2013 , Volume 8 , Issue 9, e74361
(STEM ALPHA.1 # 5110)

Collagen media

D Chiron et al. 2013 Autocrine insulin-like growth factor 1 and stem cell factor but not interleukin 6 support self-renewal of human myeloma cells Blood Cancer Journal (2013) 3, e120; doi:10.1038/bcj.2013.18
(STEM ALPHA.3 #5310)

Emmanuelle Menoret, et al, 2008. IL-21 Stimulates Human Myeloma Cell Growth through an Autocrine IGF-1 Loop. The Journal of Immunology, 6837-6842.
(STEM ALPHA.III # 5310)

Haematopietics stem cells media

Marija Vlaski, et al. 2009. Low oxygen concentration as a general physiologic regulator of erythropoiesis beyond the EPO-related downstream tuning and a tool for the optimization of red blood cell production ex vivo . Experimental Hematology, 37, Issue 5, May 2009, 573-584.

Krstic A., et al. 2009. Low O2 concentrations enhance the positive effect of IL-17 on the mainteance of erythroid progenitors during co-culture of CD34+ and mesenchymal stem cells. European cytokine network, 20, number 1, 10-6.

Ivanovic Z., 2009. Physiological, ex vivo cell oxygenation is necessary
for a true insight into cytokine biology. Eur. Cytokine Netw., 20 n° 1, 2009, 7-9, REVIEW ARTICLE.

Ivanovic Z., 2009. Hypoxia or In Situ Normoxia: The Stem Cell Paradigm. J. Cell. Physiol. 219: 271–275, 2009.

Belloc F., et al, 2009. The stem cell factor c KIT pathway must be inhibited to enable apoptosis induced by BRC-ABL inhibitors in chronic myelogenous leukemia cells. Leukemia, 2009, 1-7.

Pigneux A., et al, 2008. Triptolide cooperates with chemotherapy to induce apoptosis in acute myeloid leukemia cells. Experimental Hematology, EXPHEM2374_proof _ 16-9-2008 0.

Emmanuelle Me´noret, et al, 2008. IL-21 Stimulates Human Myeloma Cell Growth through an Autocrine IGF-1 Loop. The Journal of Immunology, 6837-6842.

Smadja D., et al, (2008). Bone Morphogenetic Proteins 2 and 4 Are Selectively Expressed by Late Outgrowth Endothelial Progenitor Cells and Promote Neoangiogenesis, Arterioscler. Thromb. Vasc. Biol.., 2008, 1-7.

Chabanon A., et al, 2008. A CROSS-TALK between SDF-1 and TGF-β CONTROLS THE QUIESCENCE/CYCLING SWITCH OF CD34+ PROGENITORS THROUGH FoxO3 AND mTOR. Stem Cells, 2008; doi:10.1634/stemcells.2008-0219.

James C., et al., 2008. The hematopoietic stem cell compartment ok JAK2V617F positive myeloproliferative disorders is a reflection of disease heterogeneity. Blood, (2008), 112, n°6, 2429-2438.

Giuliani M, et al., 2008. Generation of a Novel Regulatory NK Cell Subset from Peripheral Blood CD34+ Progenitors Promoted by Membrane-Bound IL-15. PloS ONE (2008), 3, Issue 5, e2241, 1-16.

Tiedt R, et al, 2008. Ratio of mutant JAK2-V617F of wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood (2008), 111 : 3931-3940.

Larghero J, et al, 2008. Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cells from patients with systemic sclerosis. Ann Rheum Dis (2008), 67 : 443-449.

Panterne B, et al, 2007. Le test clonogénique CFU-GM dans le contexte du contrôle externe des CSH, AFSSAPS – DLC St Denis.

Colette M., et al (2007). Crucial role of phosphatase CD45 in determining signalling and proliferation of human myeloma cells, Eur cytokine Netw., vol 18 n°3, 2007, 1-7.

Arnulf B. et al. (2007) Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma. Leukemia, (2007), 21, 158-163.

Robert-Richard E., Ged C., Ortet J., Santarelli X., Lamrissi-Garcia I., De Verneuil H., Mazurier F. (2006). Human cell engraftment after busulfan or irradiation conditioning of NOD/SCID mice. Haematologica 2006, 91 : 1384-1387.

Hermitte F., Brunet de la Grange P., Belloc F., Praloran V. and Ivanovic Z. (2006) Very low O2 concentration (0.1%) favors G0 return dividing CD34+ cells. Stem Cells, 24, 1, 2006, 65-73.

Dobo I., et al. (2006). Abnormal peripheral blood progenitors are consistently observed after cell culture in myelodysplasic syndrome (MDS), allowing the diagnosis of eraly step of the disorder. Haematologica, 2006, 91 (s1-0945), 11è Congress of the European Hematology Association.

Girodon F. et al. Is ageing associated with a decrease of BFU-E or CFU-GM growth pattern studied by in vitro cultures ?

Ivanovic Z. et al. (2006) Transplantation and cellular engineering. Whole-blood leukodepletion filters as a source of CD34+ progenitors potentially usable in cell therapy. Transfusion, 46, 1, 118-125.

PANTERNE B, et al. Bilan 2003 – 2004 du contrôle externe des cellules souches hématopoïétiques. Cas des Moelles osseuses et des CSP décongelées, SFTS 2005, poster AFSSAPS.

Isabelle Corre-Buscail, Danielle Pineau, Marjorie Boissinot and Sylvie Hermouet , 2005. Erythropoietin-independent erythroid colony formation by bone marrow progenitors exposed to interleukin-11 and interleukin-8. Experimental Hematology, Volume 33, Issue 11, November 2005, Pages 1299-1308.

Lataillade JJ., et al., 2005. Phenotypic and functional characteristics of CD34+ cells are related to their anatomical environment : is their versatility a prerequisite for their bio-availability ? Journal of Leukocyte Biology, 77 : 634-643.

J. van Grevenynghe et al. (2005) Human CD34-positive hematopoietic stem cells constitue targets for carcinogenic polycyclic aromatic hydrocarbons. JPET 314 : 693-702.

Giron-Michel J., …. and Azzarone B. Membrane bound and soluble IL-15/IL-15Ra complexes display differential signaling and functions on human hematopoietic progenitors. Blood, 1 october 2005, 106, 7, 2302-2310.

Atfi A, Abécassis L and Bourgeade MF. Brc-Abl activates the AKT/FoxO3 signalling pathway to restrict transforming growth factor-b-mediated cytostatic signals. EMBO reports AOP, 19 august 2005.

Andre-Garnier E, Milpied N, Boutolleau D, Saiagh S, Billaudel S and Imbert-Marcille B-M (2004). Reactivation of human herpesvirus + during ex vivo expansion of circulating CD34+ haematopoietic stem cells. J Gen Virol. 85, 3333-3336.

Ivanovic Z., 2004. Interleukine-3 and ex vivo maintenance of hematopoietic stem cells : facts and controversies. Eur. Cytokine Netw, 15, 6-13.

Ivanovic Z, Hermitte F, Brunet de la Grange P, Dazey B, Belloc F, Lacombe F, Vezon G and Praloran V. (2004) Simultaneous maintenance of human cord blood SCID-repopulating cells and expansion of commited progenitors at low O2 concentration (3%). Stem Cell 03 -0131.R1.

Dobo I, Pineau D, Robillard N, Genevieve F, Piard N, Zandecki M, Hermouet S. Standardization of the CFU-GM Assay: Advantages of Plating a Fixed Number of CD34(+) Cells in Collagen Gels. J Hematother Stem Cell Res. (2003) Oct ; 12 (5) : 543-51.

Boudard D., Viallet A., Piselli S., Guyotat D. and Campos L. (2003) In vitro study of stromal cell defects in myelodysplastic syndromes, Haematologica, 88 : 827-829.

De Bruyn C., et al (2003). Ex vivo myeloid differenciation of cord blood CD34+ cells : comparison of four sreum-free media containing bovine or human albumin, Cytotherapy, 5, no 2, 153-160 .

De Bruyn C., et al (2003). Ex vivo expansion of neutrophil precursor cells from fresh and cryopreserved cord blood cells, Cytotherapy, 5, no 1, 87-98.

Stephane Prost, Magali LeDiscorde, Rima Haddad, Jean-Claude Gluckman, Bruno Canque and Marek Kirszenbaum, 2002. Characterization of a Novel Hematopoietic Marker Expressed from Early Embryonic Hematopoietic Stem Cells to Adult Mature Lineages, Blood Cells, Molecules, and Diseases, Volume 29, Issue 2, September 2002, Pages 236-248.

Lataillade JJ., Clay D., Bourin P., Hérodin F., Dupuy C., Jasmin C. and Le Bousse-Kerdiles MC. (2002). Stromal cell-derived factor 1 regulates primitive hematopiesis by suppressing apoptosis and by promoting G0/G1 transition in CD34+ cells : evidence for an autocrine/paracrine mechanism. Blood, 99, 4, 1117-1129.

Brunet de la Grange P., Ivanovic Z., Leprivey-Lorgeot V. and Praloran V. (2002). Angiotensin II that reduces the colony-forming ability of hematopoietic progenitors in serum free medium has an inverse effect in serum-supplemented medium, Stem Cells, 20 : 269-271.

Desplat V., Faucher J-L., Mahon F-X., Dello Sbarba P., Praloran V. and Ivanovic Z. (2002). Hypoxia modifies proliferation and differentiation of CD34+ CML cells, STEM CELLS, 20 : 347-354.

Boudard D, Viallet A, Piselli S, Licari D, Guyotat D and Campos L. (2002) A multiparametric study of bone marrow stromal cells in myelodisplasic syndromes (article accepté dans Leukemia).

Dobo I., et al. (2001). Comparison of four serum-free, cytokine-free media for analysis of endogenous erythroid colony growth in polycythemia vera and essential thrombocytemia. The hematology journal, 2, 396-403.

Tanja Rossmanith, 2001. Kultivierung von CD34+ -Zellen aus NabelSchnurblut zur ex vivo expansion von Stamm-und Vorlauferzellen und unterschungen zu deren homing-fahigkeiten.

Sabatini C., Panterne B., MouilloT L (2000). Comparaison de milieux semi-solides prêts à l’emploi pour le test clonogénique des progéniteurs CFU-GM. XXème Congrès de la Société Française de Transfusion Sanguine. Paris le 27-29 Juin 2000.Transfusion Clinique et Biologique vol.7 n°3 P314.

Lataillade J-J., et al. (2000). Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines : possible role in progenitor survival, Blood, 95, 756-768.

Abnese P., Leboeuf M., Rosa J-P. and Uzan G. (2000). Identification of GATA-overlaping sequence within the enhancer of the murine GPIIb promoter that induces transcriptional deregulation in human K562 cells, Blood, 96, 4, 1348-1357.

Lepage A., Leboeuf M., Cazenave J-P., De la salle C., Lanza F. and Uzan G. (2000). The aIIIbb3 integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34+ cord blood cells to megacaryocytes, Blood, 96, 13, 4169-4177.

Production de Vaccins (Grippe)

Morphological and Proliferative Characteristics of Vero and MDCK Cells during Culturing in Nutrient Media on the Basis of Hydrolysates of Plant Proteins.
N A Mazurkova, E I Ryabchikova, G P Troshkova, T N Getmanova, T P Sumkina, L N Shishkina, A N Sergeev
Federal State Institution of Science, State Research Center of Virology and Biotechnology « Vector », Russian Consumer Supervision, Novosibirsk oblast, Kol’tsovo.
Bulletin of Experimental Biology and Medicine (impact factor: 0.27). 05/2009; 147(4):551-4.

Evaluation of properties of chitosan as an adjuvant for inactivated influenza vaccines administered parenterally
Yuri Ghendon*, Stanislav Markushin, Yuri Vasiliev, Irina Akopova, Irina Koptiaeva, Georgy Krivtsov, Olga Borisova, Nelly Ahmatova, Ekaterina Kurbatova, Svetlana Mazurina, Valentina Gervazieva
Journal of Medical Virology
Volume 81, Issue 3, pages 494–506, March 2009

Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
The use of components of plant origin in the development of production technology for live cold-adapted cultural influenza vaccine 2008

N. A. Mazurkova, T. D. Kolokol’tsova, E. A. Nechaeva, L. N. Shishkina and A. N. Sergeev
From the issue entitled « This issue is a translation of Byulleten’ Eksperimental’noi Biologii i Meditsiny (Bulletin of Experimental Biology and Medicine) and Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine) »

Y. Genzel, M. Fischer and U. Reichl Serum-free influenza virus production avoiding washing steps and medium exchange in large-scale microcarrier culture Vaccine, Volume 24, Issue 16, 12 April 2006, Pages 3261-3272

Y.Z. Ghendon, S.G. Markushin, I.I. Akopova, I.B. Koptiaeva, E.A. Nechaeva, L.A. Mazurkova, I.F. Radaeva and T.D. Kolokoltseva Development of cell culture (MDCK) live cold-adapted (CA) attenuated influenza vaccine Vaccine, Volume 23, Issue 38, 7 September 2005, Pages 4678-4684

Elena Nechaeva, Nataliya Mazurkova, Yuri Gendon, Tamara Kolokoltsova, New Technology for Producing -Live Influenza Vaccine Using a Serum-Free Medium Supplemented with Additives and Stabilizers of Plant Origin. Bioprocess international, 2004.

Andre-Garnier E, Milpied N, Boutolleau D, Saiagh S, Billaudel S and Imbert-Marcille B-M (2004). Reactivation of human herpesvirus + during ex vivo expansion of circulating CD34+ haematopoietic stem cells. J Gen Virol. 85, 3333-3336.

Media : producing-live influenza vaccine

Y. Genzel, M. Fischer and U. Reichl Serum-free influenza virus production avoiding washing steps and medium exchange in large-scale microcarrier culture Vaccine, Volume 24, Issue 16, 12 April 2006, Pages 3261-3272

Y.Z. Ghendon, S.G. Markushin, I.I. Akopova, I.B. Koptiaeva, E.A. Nechaeva, L.A. Mazurkova, I.F. Radaeva and T.D. Kolokoltseva Development of cell culture (MDCK) live cold-adapted (CA) attenuated influenza vaccine Vaccine, Volume 23, Issue 38, 7 September 2005, Pages 4678-4684

Elena Nechaeva, Nataliya Mazurkova, Yuri Gendon, Tamara Kolokoltsova, New Technology for Producing -Live Influenza Vaccine Using a Serum-Free Medium Supplemented with Additives and Stabilizers of Plant Origin. Bioprocess international, 2004.

Hypoxie / Hypercapnie STEM ALPHA.S3

CD34+ cells obtained from “good mobilizers” are more activated and …
de Z Ivanovic – 2010 – As described recently,13 CD34+ cells (50 × 103/mL) were resuspended in serum-free, cytokine-free liquid storage medium (Stem alpha S3, … onlinelibrary.wiley.com › … › Journal Home › Vol 50 Issue

Marija Vlaski, et al. 2009. Low oxygen concentration as a general physiologic regulator of erythropoiesis beyond the EPO-related downstream tuning and a tool for the optimization of red blood cell production ex vivo . Experimental Hematology, 37, Issue 5, May 2009, 573-584.

Krstic A., et al. 2009. Low O2 concentrations enhance the positive effect of IL-17 on the mainteance of erythroid progenitors during co-culture of CD34+ and mesenchymal stem cells. European cytokine network, 20, number 1, 10-6.

Ivanovic Z., 2009. Physiological, ex vivo cell oxygenation is necessary
for a true insight into cytokine biology. Eur. Cytokine Netw., 20 n° 1, 2009, 7-9, REVIEW ARTICLE.

Ivanovic Z., 2009. Hypoxia or In Situ Normoxia: The Stem Cell Paradigm. J. Cell. Physiol. 219: 271–275, 2009.

[PDF] 2006
2006 résumés pjets financés AOR greffe
Format de fichier: PDF/Adobe Acrobat – Afficher
Stem Alpha S3 sera utilisée soit sans cytokine (2 équipes participantes), … métylcellulose préfabriquée (Stem Alpha 1D). ; Les cellules souches …
www.agence-biomedecine.fr/uploads/…/AORGreffe2006.pdf

Ivanovic Z. et al. (2006) Transplantation and cellular engineering. Whole-blood leukodepletion filters as a source of CD34+ progenitors potentially usable in cell therapy. Transfusion, 46, 1, 118-125.

Milieu liquide sans sérum STEM ALPHA.A

En 2013
PATENT LATAILLADE, Jean-Jacques ; LE BOUSSE-KERDILES, Marie-Caroline 2013 IN VITRO MODELLING OF HAEMATOPOIETIC STEM CELL MEDULLARY NESTS: A TOOL FOR STUDYING THE REGULATION OF HAEMATOPOIESIS, EVALUATING THE NESTING POTENTIAL OF A HAEMATOPOIETIC GRAFT AND TESTING THE PHARMACOTOXICOLOGY OF MEDICAMENTS WIPO Patent Application WO/2013/024096
(STEM ALPHA.A # 5510)

En 2012
Mohammad Hammoud et al. 2012. Combination of low O2 concentration and mesenchymal stromal cells during culture of cord blood CD34+ cells improves the maintenance and proliferative capacity of hematopoietic stem cells.
Article first published online: 24 FEB 2012 DOI: 10.1002/jcp.23019
Journal of Cellular Physiology Vol 227, Issue 6, p. 2750–2758, June 2012

En 2011
Negrini S. et al. 2011 Membrane-bound IL-15 stimulation on peripheral blood natural kiler progenitors leads to the generation of an adherent subset co-expressing dendritic cells and natural kiler functional markers Haematologica. 2011 May; 96(5): 762–766. (STEM ALPHA.A #5510)
www.haematologica.org/cgi/reprint/haematol.2010.033738v1.pdf

En 2010
Modeling of congenital erythropoietic porphyria by RNA interference: a new tool for preclinical gene therapy evaluation
Elodie Robert-Richard1,2, Magalie Lalanne1,2, Isabelle Lamrissi-Garcia1,2, Véronique Guyonnet-Duperat1, Emmanuel Richard1,2, Vincent Pitard2,3, Fréderic Mazurier1,2, François Moreau-Gaudry1,2, Cécile Ged1,2, Hubert de Verneuil1,2,*
The Journal of Gene Medicine
Volume 12, Issue 8, pages 637–646, August 2010

En 2009
Low O2 concentrations enhance the positive effect of IL-17 on the maintenance of erythroid progenitors during co-culture of CD34+ and mesenchymal stem cells
Eur. Cytokine Netw., Vol. 20 n° 1, March 2009, 10-6

Aleksandra Krstić1, Marija Vlaski2,3, Mohammad Hammoud2, Jean Chevaleyre2,
Pascale Duchez2, Gordana Jovčić1, Diana Bugarski1, Pavle Milenković1, Philippe Bourin4,Jean-Michel Boiron2,3, Vincent Praloran3,5, Zoran Ivanović2
1 Institute for Medical Research, Belgrade University, Belgrade, Serbia
2 French Blood Institute, Aquitaine-Limousin Branch, 5, place Amélie Raba Léon, BP 24, 33035 Bordeaux Cedex, France
3 Victor-Ségalen University (Bordeaux 2), Bordeaux, France
4 French Blood Institute, Pyrénées-Méditerranée Branch, Toulouse, France
5 CNRS UMR 5164 Correspondence: Z. Ivanovic, MD, PhD, Etablissement Français du Sang Aquitaine-Limousin, 5 place Amélie Raba Léon, BP 24,
33035 Bordeaux Cedex, France <zoran.ivanovic@efs.sante.fr> Accepted for publication January 16, 2009

Tissue inhibitors of matrix metalloproteinases in platelets and megakaryocytes: A novel organization for these secreted proteins
Julien Villeneuve, Anna Block Marie-Caroline Le Bousse-Kerdilès, Sébastien Lepreux Paquita Nurden
Jean Ripoche Alan T. Nurden
Experimental Hematology Volume 37, Issue 7 , Pages 849-856, July 2009

Pascale Flandrin et al. 2008 Significance of heat-shock protein (HSP) 90 expression in acute myeloid leukemia cells Cell Stress and Chaperones (2008) 13:357–364 (STEM ALPHA.A # 5510)
Review of Althought – Definition and Scientific Information – Page 1
… detected was similar in all media tested: 29 +- 10% in Stem alpha-A, 28 +- 9,7% in Stemalpha-AMK, 28 +-7,7% in Stemalpha-AMK+TPO For normal subjects, … eurekamag.com/keyword/a/187/althought.php – États-Unis

2008 and before 2008
Giuliani M, et al., 2008. Generation of a Novel Regulatory NK Cell Subset from Peripheral Blood CD34+ Progenitors Promoted by Membrane-Bound IL-15. PloS ONE (2008), 3, Issue 5, e2241, 1-16.

Hermitte F., Brunet de la Grange P., Belloc F., Praloran V. and Ivanovic Z. (2006) Very low O2 concentration (0.1%) favors G0 return dividing CD34+ cells. Stem Cells, 24, 1, 2006, 65-73.

Giron-Michel J., …. and Azzarone B. Membrane bound and soluble IL-15/IL-15Ra complexes display differential signaling and functions on human hematopoietic progenitors. Blood, 1 october 2005, 106, 7, 2302-2310

Ivanovic Z., 2004. Interleukine-3 and ex vivo maintenance of hematopoietic stem cells : facts and controversies. Eur. Cytokine Netw, 15, 6-13.

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Cell.souches / Progéniteurs : Leucémies

The peripheral CD138+ population but not the CD138) population contains myeloma clonogenic cells in plasma cell leukaemia patients 2011 Blackwell Publishing Ltd, British Journal of Haematology doi:10.1111/j.1365-2141.2011.08904.x David Chiron, Sylvanie Surget, Sophie Maı¨ga, Re´gis Bataille, , Philippe Moreau, , Steven Le Gouil, Martine Amiot, , Catherine Pellat-Deceunynck

Leukemia 24, 601-612 (March 2010)
Functional characterization of high levels of meningioma 1 as collaborating oncogene in acute leukemia
T Liu, D Jankovic, L Brault, S Ehret, F Baty, V Stavropoulou, V Rossi, A Biondi and J Schwaller

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Pigneux A., et al, 2008. Triptolide cooperates with chemotherapy to induce apoptosis in acute myeloid leukemia cells. Experimental Hematology, EXPHEM2374_proof _ 16-9-2008 0.

Emmanuelle Me´noret, et al, 2008. IL-21 Stimulates Human Myeloma Cell Growth through an Autocrine IGF-1 Loop. The Journal of Immunology, 6837-6842.

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