[en] BACKGROUND AIMS: Hematopoietic (HPC), mesenchymal (MPC) and/or endothelial (EPC) progenitor cells are being studied to repair the myocardium after acute or chronic ischemia. We examined marrow response to myocardial infarction (MI) and the ability of granulocyte-colony-stimulating factor (G-CSF) to enhance mobilization of HPC, MPC and EPC in peripheral blood (PB) and bone marrow (BM) of MI mice. METHODS: We induced MI in C57Bl/6 mice, while sham-operated (SO) animals were similarly operated on but without coronary artery ligation. Animals were treated with either saline or G-CSF, from day -5 to day +5 after MI or from day 0 to day +5. Progenitor cell numbers in PB and BM were evaluated by fluorescence-activated cell sorting (FACS) analysis and cell culture. RESULTS: White blood cells (WBC) decreased in BM and increased in PB after MI; G-CSF amplified this effect in BM but not in PB. HPC numbers decreased in BM after MI, while HPC and granulocyte-macrophage colony-forming units (GM-CFU) increased in PB only after G-CSF treatment, and more prominently so in MI than in SO mice. MPC and fibroblast-colony-forming units (F-CFU) as well as EPC were mobilized into the PB after MI and further after G-CSF treatment. Plasma troponin T concentrations decreased after G-CSF treatment. CONCLUSIONS: BM is globally affected by acute MI, but not simple body injury, with intense mobilization of marrow MPC and EPC into the PB but inhibition of HPC. Progenitor cell entry into the PB may be paralleled by depletion of their BM pools. G-CSF is required for HPC mobilization and enhances MPC and EPC entry into the PB.
Disciplines :
Hematology
Author, co-author :
Delgaudine, Marie ; Centre Hospitalier Universitaire de Liège - CHU > Radiothérapie
Gothot, André ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Beguin, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Language :
English
Title :
Spontaneous and granulocyte–colony-stimulating factor-enhanced marrow response and progenitor cell mobilization in mice after myocardial infarction.
Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, et al. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: results of the TOPCARE-CHD Registry. Circ Res. 2007;100: 1234-41.
Iso Y, Spees JL, Serrano C, Bakondi B, Pochampally R, Song YH, et al. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment. Biochem Biophys Res Commun. 2007;354:700-6.
Fujita J, Mori M, Kawada H, Ieda Y, Tsuma M, Matsuzaki Y, et al. Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair. Stem Cells. 2007;25:2750-9.
Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428:664-8.
Nygren JM, Jovinge S, Breitbach M, Sawen P, Roll W, Hescheler J, et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med. 2004;10:494-501.
Kawada H, Fujita J, Kinjo K, Matsuzaki Y, Tsuma M, Miyatake H, et al. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood. 2004;104:3581-7.
Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111:2981-7.
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999-1007.
Kurdi M, Booz GW G-CSF-based stem cell therapy for the heart: unresolved issue. A. Paracrine actions, mobilization, and delivery. Congest Heart Fail. 2007;13:221-7.
Pitchford SC, Furze RC, Jones CP, Wengner AM, Rankin SM. Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell. 2009;4:62-72.
Peister A, Mellad JA, Wang M, Tucker HA, Prockop DJ. Stable transfection of MSCs by electroporation. Gene Ther. 2004;11:224-8.
Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95: 952-8.
Rohde E, Bartmann C, Schallmoser K, Reinisch A, Lanzer G, Linkesch W, et al. Immune cells mimic the morphology of endothelial progenitor colonies in vitro. Stem Cells. 2007; 25:1746-52.
Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli I, Rosso R, et al. Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood. 2005;105:199-206.
Wojakowski W, Tendera M, Mchalowska A, Majka M, Kucia M, Maslankiewicz K, et al. Mobilization of CD34/ CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004;110:3213-20.
Roberts N, Xiao Q, Weir G, Xu Q, Jahangiri M. Endothelial progenitor cells are mobilized after cardiac surgery. Ann Thorac Surg. 2007;83:598-605.
Yin Y, Zhao X, Fang Y, Yu S, Zhao J, Song M, Huang L. SDF-1alpha involved in mobilization and recruitment of endothelial progenitor cells after arterial injury in mice. Cardiovasc Pathol. 2009. In press.
Wang Y, Johnsen HE, Mortensen S, Bindslev L, Ripa RS, Haack-Sorensen M, et al. Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention. Heart. 2006;92:768-74.
Dai Y, Ashraf M, Zuo S, Uemura R, Dai YS, Wang Y, et al. Mobilized bone marrow progenitor cells serve as donors of cytoprotective genes for cardiac repair. J Mol Cell Cardiol. 2008;44:607-17.
Brehm M, Ebner P, Picard F, Urbien R, Turan G, Strauer BE. Enhanced mobilization of CD34(+) progenitor cells expressing cell adhesion molecules in patients with STEMI. Clin Res Cardiol. 2009;98:477-86.
Norol F, Merlet P, Isnard R, Sebillon P, Bonnet N, Cailliot C, et al. Infl uence of mobilized stem cells on myocardial infarct repair in a nonhuman primate model. Blood. 2003;102: 4361-8.
Ellis SG, Penn MS, Bolwell B, Garcia M, Chacko M, Wang T, et al. Granulocyte colony stimulating factor in patients with large acute myocardial infarction: results of a pilot dose-escalation randomized trial. Am Heart J. 2006; 152:1051-14.
Wang Y, Ripa RS, Jorgensen E, Hesse B, Mortensen S, Kastrup J. Mobilization of haematopoietic and non-haematopoietic cells by granulocyte-colony stimulating factor and vascular endothelial growth factor gene therapy in patients with stable severe coronary artery disease. Scand Cardiovasc J. 2007;41:397-404.
Kassis I, Zangi L, Rivkin R, Levdansky L, Samuel S, Marx G, et al. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. 2006;37:967-76.
Liu ZJ, Zhuge Y, Velazquez OC. Trafficking and differentiation of mesenchymal stem cells. J Cell Biochem. 2009; 106:984-91.
Mansilla E, Marin GH, Drago H, Sturla F, Salas E, Gardiner C, et al. Bloodstream cells phenotypically identical to human mesenchymal bone marrow stem cells circulate in large amounts under the infl uence of acute large skin damage: new evidence for their use in regenerative medicine. Transplant Proc. 2006;38:967-9.
Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2000;2:477-88.
Tatsumi K, Otani H, Sato D, Enoki C, Iwasaka T, Imamura H, et al. Granulocyte-colony stimulating factor increases donor mesenchymal stem cells in bone marrow and their mobilization into peripheral circulation but does not repair dystrophic heart after bone marrow transplantation. Circ J. 2008;72:1351-8.
Lund TC, Tolar J, Orchard PJ. Granulocyte colony-stimulating factor mobilized CFU-F can be found in the peripheral blood but have limited expansion potential. Haematologica. 2008;93:908-12.
Ripa RS, Haack-Sorensen M, Wang Y, Jorgensen E, Mortensen S, Bindslev L, et al. Bone marrow derived mesenchymal cell mobilization by granulocyte-colony stimulating factor after acute myocardial infarction: results from the Stem Cells in Myocardial Infarction (STEMMI) trial. Circulation. 2007;116:I24-30.
Kong D, Melo LG, Gnecchi M, Zhang L, Mostoslavsky G, Liew CC, et al. Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injured arteries. Circulation. 2004;110:2039-46.
Case J, Mead LE, Bessler WK, Prater D, White HA, Saadatzadeh MR, et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol. 2007;35: 1109-18.
Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109:1801-9.
Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001;98:10344-9.
Ince H, Petzsch M, Kleine HD, Schmidt H, Rehders T, Korber T, et al. Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulo-cyte-colony-stimulating factor (FIRSTLINE-AMI). Circulation. 2005;112:3097-106.
Ai G, Su Y, Yan G, Wang M, Liu X, Xu H, et al. [The experimental study of bone marrow mesenchymal stem cells on the repair of skin wound combined with local radiation injury]. Zhonghua Yi Xue Za Zhi. 2002;82:1632-6.
Cheng Z, Liu X, Ou L, Zhou X, Liu Y, Jia X, et al. Mobilization of mesenchymal stem cells by granulocyte colony-stimulating factor in rats with acute myocardial infarction. Cardiovasc Drugs Ther. 2008;22:363-71.
Sesti C, Hale SL, Lutzko C, Kloner RA. Granulocyte colony-stimulating factor and stem cell factor improve contractile reserve of the infarcted left ventricle independent of restoring muscle mass. J Am Coll Cardiol. 2005;46: 1662-9.
Sugano Y, Anzai T, Yoshikawa T, Maekawa Y, Kohno T, Mahara K, et al. Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction. Cardiovasc Res. 2005;65:446-56.
Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H, et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyo-cytes. Nat Med. 2005;11:305-11.
Iwanaga K, Takano H, Ohtsuka M, Hasegawa H, Zou Y, Qin Y, et al. Effects of G-CSF on cardiac remodeling after acute myocardial infarction in swine. Biochem Biophys Res Commun. 2004;325:1353-9.
Takahama H, Mnamino T, Hirata A, Ogai A, Asanuma H, Fujita M, et al. Granulocyte colony-stimulating factor mediates cardioprotection against ischemia/reperfusion injury via phosphatidylinositol-3-kinase/Akt pathway in canine hearts. Cardiovasc Drugs Ther. 2006;20:159-65.
Ueda K, Takano H, Hasegawa H, Niitsuma Y, Qin Y, Ohtsuka M, et al. Granulocyte colony stimulating factor directly inhibits myocardial ischemia-reperfusion injury through Akt-endothelial NO synthase pathway. Arterioscler Thromb Vasc Biol. 2006;26:e108-13.
Engelmann MG, Theiss HD, Hennig-Theiss C, Huber A, Wintersperger BJ, Werle-Ruedinger AE, et al. Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI(Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocar-dial Infarction) trial. J Am Coll Cardiol. 2006;48:1712-21.
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, et al. Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999;5:434-8.
Brunner S, Huber BC, Fischer R, Groebner M, Hacker M, David R, et al. G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells. Exp Hematol. 2008;36:695-702.
Roberts AW, Foote S, Alexander WS, Scott C, Robb L, Metcalf D. Genetic infl uences determining progenitor cell mobilization and leukocytosis induced by granulocyte colony-stimulating factor. Blood. 1997;89:2736-44.
Lucas D, Battista M, Shi PA, Isola L, Frenette PS. Mobilized hematopoietic stem cell yield depends on species-specific circadian timing. Cell Stem Cell. 2008;3:364-6.
