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Published in: Clinical Research in Cardiology 8/2009

01-08-2009 | Original Paper

Enhanced mobilization of CD34+ progenitor cells expressing cell adhesion molecules in patients with STEMI

Authors: Michael Brehm, Petra Ebner, Frauke Picard, Ryan Urbien, Gökmen Turan, Bodo-Eckehard Strauer

Published in: Clinical Research in Cardiology | Issue 8/2009

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Abstract

Background

Adult stem cells can contribute to myocardial regeneration after ischemic injury. The aim of the study was to determine (1) the amount of mobilized CD34+/CD117+, CD34+/KDR+ cells into peripheral blood (PB) in relation to inflammatory and haematopoietic cytokines, (2) the presence of circulating CD34+ cells, expressing cell adhesion molecules (CAM), in patients with ST-segment elevation myocardial infarction (STEMI) in comparison to patients with coronary artery disease (CAD).

Materials and methods

Twenty-three patients with STEMI (<12 h), 24 patients with CAD and 15 control subjects were enrolled in this study. The patients were matched in age, 2-CAD, ejection fraction (45%) and end-diastolic volume index (70 ml/m2). The number of stem cells and the expression of adhesion molecules were quantified by use of flow cytometry. Inflammatory cytokines [interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor] and chemotactic factors as stromal cell-derived factor-1 (SDF-1), hepatocyte growth factor (HGF) were determined by ELISA.

Results

The amount of circulating progenitor cells including CD34+/CD117+ and CD34+/KDR+ cells was significantly higher in patients with STEMI than in patients with CAD (CD34+/CD117+ 433 ± 128 vs. 100 ± 17, P = 0.012; CD34+/KDR+ 253 ± 41 vs. 128 ± 24, P = 0.02). The mobilization of CD34+ progenitor cells expressing CXCR4-receptor, lymphocyte function-associated antigen-1 (LFA-1), very late antigen-4 (VLA-4) and ICAM-1 into PB was significantly higher in patients with STEMI compared to CAD (CD34+/CXCR4+ 740 ± 327 vs. 136 ± 23, P = 0.006; CD34+/LFA-1 976 ± 227 vs. 329 ± 41, P = 0.025; CD34+/VLA4+ 830 ± 161 vs. 330 ± 31, P = 0.007; CD34+/ICAM+ 387 ± 66 vs. 144 ± 26, P < 0.001). Additionally, the cytokines G-CFS, IL-6 and HGF were upregulated and significantly increase in the STEMI group compared with controls and CAD (G-CSF 50.6 ± 6.8 vs. 23 ± 3 vs. 23.8 ± 2, P Co vs. STEMI < 0.001, P Co vs. CAD = n.s., P STEMI vs. CAD < 0.001; IL-6 8.4 ± 0.6 vs. 3.8 ± 1.9 vs. 2.6 ± 1, P Co vs. STEMI < 0.001, P Co vs. CAD = n.s., P STEMI vs. CAD < 0.001; HGF 4,502 ± 461 vs. 686 ± 195 vs. 1,746 ± 461, P Co vs. STEMI < 0.001, P Co vs. CAD = n.s., P STEMI vs. CAD < 0.001), while the level of SDF-1 was increased in patients with CAD compared to controls and patients with STEMI (3,035 ± 286 vs. 2,028 ± 76 vs. 2,154 ± 234, P Co vs. STEMI = n.s., P Co vs. CAD = n.s., P STEMI vs. CAD = 0.005).

Conclusions

The study demonstrates in patients with STEMI an increased mobilization of progenitor cells like CD34+/CD117+ and CD34+/KDR+ compared to CAD. Furthermore, we could shown that in patients with STEMI the mobilization of CD34+ progenitor cells with expressed CAM was increased. It is to speculate that an enhanced expression of adhesion molecules may increase the transmigration and implantation of progenitor cells into ischemic myocardium for myocardial repair.
Literature
1.
go back to reference Strauer BE, Brehm M, Zeus T, Gattermann N, Hernandez A, Sorg RV et al (2001) Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr 126:932–938PubMedCrossRef Strauer BE, Brehm M, Zeus T, Gattermann N, Hernandez A, Sorg RV et al (2001) Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr 126:932–938PubMedCrossRef
2.
go back to reference Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV et al (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918PubMedCrossRef Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV et al (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918PubMedCrossRef
3.
go back to reference Assmus B, Schaechinger V, Teupe C, Britten M, Lehmann R, Döbert N et al (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 106:3009–3017PubMedCrossRef Assmus B, Schaechinger V, Teupe C, Britten M, Lehmann R, Döbert N et al (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 106:3009–3017PubMedCrossRef
4.
go back to reference Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C et al (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148PubMedCrossRef Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C et al (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148PubMedCrossRef
5.
7.
go back to reference Forrester JS, Price MJ, Makkar RR (2003) Stem cell repair of infarcted myocardium: an overview for clinicians. Circulation 108:1139–1145PubMedCrossRef Forrester JS, Price MJ, Makkar RR (2003) Stem cell repair of infarcted myocardium: an overview for clinicians. Circulation 108:1139–1145PubMedCrossRef
8.
go back to reference Rubart M, Field LJ (2008) Stem cell differentiation: cardiac repair. Cells Tissues Organs 188:202–211PubMedCrossRef Rubart M, Field LJ (2008) Stem cell differentiation: cardiac repair. Cells Tissues Organs 188:202–211PubMedCrossRef
9.
go back to reference Bartsch T, Brehm M, Zeus T, Kögler G, Wernet P, Strauer BE (2007) Transplantation of autologues mononuclear bone marrow stem cells in patients with peripheral arterial disease (The TAM-PAD STUDY). Clin Res Cardiol 96:891–899PubMedCrossRef Bartsch T, Brehm M, Zeus T, Kögler G, Wernet P, Strauer BE (2007) Transplantation of autologues mononuclear bone marrow stem cells in patients with peripheral arterial disease (The TAM-PAD STUDY). Clin Res Cardiol 96:891–899PubMedCrossRef
10.
go back to reference Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M et al (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228PubMed Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M et al (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228PubMed
11.
go back to reference Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM et al (2001) Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 103:2885–2890PubMedCrossRef Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM et al (2001) Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 103:2885–2890PubMedCrossRef
12.
go back to reference Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M et al (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 97:3422–3427PubMedCrossRef Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M et al (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 97:3422–3427PubMedCrossRef
13.
go back to reference Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353PubMedCrossRef Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353PubMedCrossRef
14.
go back to reference Ts Li, Hamano K, Nishida M et al (2003) CD117+ stem cells play a key role in therapeutic angiogenesis induced by bone marrow cell implantation. Am J Physiol Heart Circ Physiol 285:H931–H937 Ts Li, Hamano K, Nishida M et al (2003) CD117+ stem cells play a key role in therapeutic angiogenesis induced by bone marrow cell implantation. Am J Physiol Heart Circ Physiol 285:H931–H937
15.
go back to reference Elmadbouh I, Haider HKH, Jiang S, Idris NM, Lu G, Ashraf M (2007) Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. J Mol Cell Cardiol 42:792–803PubMedCrossRef Elmadbouh I, Haider HKH, Jiang S, Idris NM, Lu G, Ashraf M (2007) Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. J Mol Cell Cardiol 42:792–803PubMedCrossRef
16.
go back to reference Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T et al (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283:845–848PubMedCrossRef Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T et al (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283:845–848PubMedCrossRef
17.
go back to reference Pillarisetti K, Gupta SK (2001) Cloning and relative expression analysis of rat stromal cell derived factor-1 (SDF-1)1: SDF-1 alpha mRNA is selectively induced in rat model of myocardial infarction. Inflammation 25:293–300PubMedCrossRef Pillarisetti K, Gupta SK (2001) Cloning and relative expression analysis of rat stromal cell derived factor-1 (SDF-1)1: SDF-1 alpha mRNA is selectively induced in rat model of myocardial infarction. Inflammation 25:293–300PubMedCrossRef
18.
go back to reference Grundmann F, Scheid C, Braun D et al (2007) Differential increase of CD34, KDR/CD34, CD133/CD34 and CD177/CD34 positive cells in peripheral blood of patients with acute myocardial infarction. Clin Res Cardiol 96:621–627PubMedCrossRef Grundmann F, Scheid C, Braun D et al (2007) Differential increase of CD34, KDR/CD34, CD133/CD34 and CD177/CD34 positive cells in peripheral blood of patients with acute myocardial infarction. Clin Res Cardiol 96:621–627PubMedCrossRef
19.
go back to reference Issekutz TB (1995) In vivo blood monocyte migration to acute inflammatory reactions, IL-1 alpha, TNF-alpha, IFN-gamma, and C5a utilizes LFA-1, Mac-1, and VLA-4. The relative importance of each integrin. J Immunol 154:6533–6540PubMed Issekutz TB (1995) In vivo blood monocyte migration to acute inflammatory reactions, IL-1 alpha, TNF-alpha, IFN-gamma, and C5a utilizes LFA-1, Mac-1, and VLA-4. The relative importance of each integrin. J Immunol 154:6533–6540PubMed
20.
go back to reference Imai K, Kobayashi M, Wang J, Ohiro Y, Hamada J, Cho Y et al (1999) Selective transendothelial migration of hematopoietic progenitor cells: a role in homing of progenitor cells. Blood 93:149–156PubMed Imai K, Kobayashi M, Wang J, Ohiro Y, Hamada J, Cho Y et al (1999) Selective transendothelial migration of hematopoietic progenitor cells: a role in homing of progenitor cells. Blood 93:149–156PubMed
21.
go back to reference Yoon CH, Hur J, Oh IY, Park KW, Kim TY, Shin JH et al (2006) Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 26:1066–1072PubMedCrossRef Yoon CH, Hur J, Oh IY, Park KW, Kim TY, Shin JH et al (2006) Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 26:1066–1072PubMedCrossRef
22.
go back to reference Duan H, Cheng L, Sun X, Wu Y, Hu L, Wang J et al (2006) LFA-1 and VLA-4 involved in human high proliferative potential-endothelial progenitor cells homing to ischemic tissue. Thromb Haemost 96:807–815PubMed Duan H, Cheng L, Sun X, Wu Y, Hu L, Wang J et al (2006) LFA-1 and VLA-4 involved in human high proliferative potential-endothelial progenitor cells homing to ischemic tissue. Thromb Haemost 96:807–815PubMed
23.
go back to reference Inoue T, Uchida T, Yaguchi I, Sakai Y, Takavangi K, Morooka S (2003) Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis. Circulation 107:1757–1763PubMedCrossRef Inoue T, Uchida T, Yaguchi I, Sakai Y, Takavangi K, Morooka S (2003) Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis. Circulation 107:1757–1763PubMedCrossRef
24.
go back to reference Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A et al (2001) Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103:2776–2779PubMedCrossRef Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A et al (2001) Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103:2776–2779PubMedCrossRef
25.
go back to reference Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K et al (2004) 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 110:3213–3220PubMedCrossRef Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K et al (2004) 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 110:3213–3220PubMedCrossRef
26.
go back to reference Damås JK, Wæhre T, Yndestad A, Ueland T, Müller F, Eiken HG et al (2002) Stromal cell-derived factor-1α in unstable angina: potential anti-inflammatory and matrix-stabilizing effects. Circulation 106:36–42PubMedCrossRef Damås JK, Wæhre T, Yndestad A, Ueland T, Müller F, Eiken HG et al (2002) Stromal cell-derived factor-1α in unstable angina: potential anti-inflammatory and matrix-stabilizing effects. Circulation 106:36–42PubMedCrossRef
27.
go back to reference Ratajczak MZ, Majka M, Kucia M, Drukala J, Pietrzkowski Z, Peiper S et al (2003) Expression of functional CXCR4 by muscle satellite cells and secretion of SDF-1 by muscle-derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and hematopoietic stem/progenitor cells in muscles. Stem Cells 21:363–371PubMedCrossRef Ratajczak MZ, Majka M, Kucia M, Drukala J, Pietrzkowski Z, Peiper S et al (2003) Expression of functional CXCR4 by muscle satellite cells and secretion of SDF-1 by muscle-derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and hematopoietic stem/progenitor cells in muscles. Stem Cells 21:363–371PubMedCrossRef
28.
go back to reference Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S et al (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischaemic neovascularization. Circulation 107:1322–1328PubMedCrossRef Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S et al (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischaemic neovascularization. Circulation 107:1322–1328PubMedCrossRef
29.
go back to reference Vandervelde S, van Luyn MJ, Tio RA, Harmsen MC (2005) Signaling factors in stem cell-mediated repair of infarcted myocardium. J Mol Cell Cardiol 39:363–376PubMedCrossRef Vandervelde S, van Luyn MJ, Tio RA, Harmsen MC (2005) Signaling factors in stem cell-mediated repair of infarcted myocardium. J Mol Cell Cardiol 39:363–376PubMedCrossRef
30.
go back to reference Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110:3300–3305PubMedCrossRef Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110:3300–3305PubMedCrossRef
31.
go back to reference Lee SH, Wolf PL, Escudero R, Deutsch R, Jamieson SW, Thistlethwaite PA (2000) Early expression of angiogenesis factors in acute myocardial ischaemia and infarction. N Engl J Med 342:626–633PubMedCrossRef Lee SH, Wolf PL, Escudero R, Deutsch R, Jamieson SW, Thistlethwaite PA (2000) Early expression of angiogenesis factors in acute myocardial ischaemia and infarction. N Engl J Med 342:626–633PubMedCrossRef
32.
go back to reference Suzuki H, Murakami M, Shoji M, Iso Y, Kondo T, Shibata M et al (2003) Hepatocyte growth factor and vascular endothelial growth factor in ischaemic heart disease. Coron Artery Dis 14:301–307PubMedCrossRef Suzuki H, Murakami M, Shoji M, Iso Y, Kondo T, Shibata M et al (2003) Hepatocyte growth factor and vascular endothelial growth factor in ischaemic heart disease. Coron Artery Dis 14:301–307PubMedCrossRef
33.
go back to reference Kmiecik TE, Keller JR, Rosen E, Vande Woude GF (1992) Hepatocyte growth factor is a synergistic factor in the growth of hematopoietic progenitor cells. Blood 80:2454–2457PubMed Kmiecik TE, Keller JR, Rosen E, Vande Woude GF (1992) Hepatocyte growth factor is a synergistic factor in the growth of hematopoietic progenitor cells. Blood 80:2454–2457PubMed
34.
go back to reference Wang Y, Ahmad N, Wani MA, Ashraf M (2004) Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis. J Mol Cell Cardiol 37:1041–1052PubMedCrossRef Wang Y, Ahmad N, Wani MA, Ashraf M (2004) Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis. J Mol Cell Cardiol 37:1041–1052PubMedCrossRef
35.
go back to reference Tambara K, Premaratne GU, Sakaguchi G, Kanemitsu N, Lin X, Nakajima H et al (2005) Administration of control-released hepatocyte growth factor enhances the efficacy of skeletal myoblast transplantation in rat infarcted hearts by greatly increasing both quantity and quality of the graft. Circulation 112(9 Suppl):I129–I134PubMed Tambara K, Premaratne GU, Sakaguchi G, Kanemitsu N, Lin X, Nakajima H et al (2005) Administration of control-released hepatocyte growth factor enhances the efficacy of skeletal myoblast transplantation in rat infarcted hearts by greatly increasing both quantity and quality of the graft. Circulation 112(9 Suppl):I129–I134PubMed
36.
go back to reference Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A et al (2005) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97:663–673PubMedCrossRef Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A et al (2005) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97:663–673PubMedCrossRef
37.
go back to reference Turan RG, Brehm M, Koestering M, Zeus T, Bartsch T, Steiner S et al (2007) Factors influencing spontaneous mobilization of CD34+ and CD133+ progenitor cells after myocardial infarction. Euro J Clin Invest 37:842–851CrossRef Turan RG, Brehm M, Koestering M, Zeus T, Bartsch T, Steiner S et al (2007) Factors influencing spontaneous mobilization of CD34+ and CD133+ progenitor cells after myocardial infarction. Euro J Clin Invest 37:842–851CrossRef
Metadata
Title
Enhanced mobilization of CD34+ progenitor cells expressing cell adhesion molecules in patients with STEMI
Authors
Michael Brehm
Petra Ebner
Frauke Picard
Ryan Urbien
Gökmen Turan
Bodo-Eckehard Strauer
Publication date
01-08-2009
Publisher
D. Steinkopff-Verlag
Published in
Clinical Research in Cardiology / Issue 8/2009
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-009-0021-5

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