CD34+ cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent

被引:131
作者
Quyyumi, Arshed A. [1 ]
Waller, Edmund K.
Murrow, Jonathan
Esteves, Fabio
Galt, James
Oshinski, John
Lerakis, Stamatios
Sher, Salman
Vaughan, Douglas [2 ]
Perin, Emerson [3 ]
Willerson, James [3 ]
Kereiakes, Dean [4 ]
Gersh, Bernard J. [5 ]
Gregory, Douglas [6 ]
Werner, Astrid [7 ]
Moss, Thomas [7 ]
Chan, Wai Shun [8 ]
Preti, Robert [8 ]
Pecora, Andrew L. [7 ,8 ]
机构
[1] Emory Univ, Sch Med, Atlanta, GA 30322 USA
[2] Northwestern Univ, Chicago, IL 60611 USA
[3] Texas Heart Inst, Houston, TX 77025 USA
[4] Christ Hosp Heart & Vasc Ctr, Cincinnati, OH 45219 USA
[5] Mayo Clin, Coll Med, Rochester, MN USA
[6] Cardiovasc Clin Studies Inc, Boston, MA USA
[7] Amorcyte Inc, Hackensack, NJ USA
[8] Progenitor Cell Therapy LLC, Allendale, NJ USA
关键词
LEFT-VENTRICULAR FUNCTION; BONE-MARROW-CELLS; MONONUCLEAR-CELLS; INTRACORONARY INJECTION; PROGENITOR CELLS; TRANSPLANTATION; HUMANS; REGENERATION; MOBILIZATION; INSIGHTS;
D O I
10.1016/j.ahj.2010.09.025
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells. Methods Patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34(+) cells were infused via the IRA at 3 dose levels (5, 10, and 15 x 10(6)) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34(+) cell mobility were performed. Results Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the >= 10 million cohorts compared with controls (-256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the >= 10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34(+) cells. Conclusions The effects of CD34(+) cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34(+) cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34(+) cells in patients with acute myocardial infarction [AMR-01] NCT00313339). (Am Heart J 2011;161:98-105.)
引用
收藏
页码:98 / 105
页数:8
相关论文
共 29 条
[1]   Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium [J].
Abbate, A ;
Bussani, R ;
Biondi-Zoccai, GGL ;
Santini, D ;
Petrolini, A ;
De Giorgio, F ;
Vasaturo, F ;
Scarpa, S ;
Severino, A ;
Liuzzo, G ;
Leone, AM ;
Baldi, F ;
Sinagra, G ;
Silvestri, F ;
Vetrovec, GW ;
Crea, F ;
Biasucci, LM ;
Baldi, A .
EUROPEAN HEART JOURNAL, 2005, 26 (19) :2039-2045
[2]  
ASSMUS B, 2009, CIRC-HEART FAIL, P1941
[3]   Evidence for Cardiomyocyte Renewal in Humans [J].
Bergmann, Olaf ;
Bhardwaj, Ratan D. ;
Bernard, Samuel ;
Zdunek, Sofia ;
Barnabe-Heider, Fanie ;
Walsh, Stuart ;
Zupicich, Joel ;
Alkass, Kanar ;
Buchholz, Bruce A. ;
Druid, Henrik ;
Jovinge, Stefan ;
Frisen, Jonas .
SCIENCE, 2009, 324 (5923) :98-102
[4]   Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI) -: Mechanistic insights from serial contrast-enhanced magnetic resonance imaging [J].
Britten, MB ;
Abolmaali, ND ;
Assmus, B ;
Lehmann, R ;
Honold, J ;
Schmitt, J ;
Vogl, TJ ;
Martin, H ;
Schächinger, V ;
Dimmeler, S ;
Zeiher, AM .
CIRCULATION, 2003, 108 (18) :2212-2218
[5]   Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up‡ [J].
Cao, Feng ;
Sun, Dongdong ;
Li, Chengxiang ;
Narsinh, Kazim ;
Zhao, Li ;
Li, Xue ;
Feng, Xuyang ;
Zhang, Jun ;
Duan, Yunyan ;
Wang, Jing ;
Liu, Dingjing ;
Wang, Haichang .
EUROPEAN HEART JOURNAL, 2009, 30 (16) :1986-1994
[6]   SEQUENTIAL MULTIVESSEL CORONARY ANGIOPLASTY ASSESSED BY TL-201 TOMOGRAPHY [J].
DEPUEY, EG ;
ROUBIN, GS ;
DEPASQUALE, EE ;
NODY, AC ;
GARCIA, EV ;
KING, SB ;
BERGER, HJ .
CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS, 1989, 18 (04) :213-221
[7]   The increasing role of quantification in clinical nuclear cardiology: The Emory approach [J].
Garcia, Ernest V. ;
Faber, Tracy L. ;
Cooke, C. David ;
Folks, Russell D. ;
Chen, Ji ;
Santana, Cesar .
JOURNAL OF NUCLEAR CARDIOLOGY, 2007, 14 (04) :420-432
[8]   Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI) [J].
Ge, J. ;
Li, Y. ;
Qian, J. ;
Shi, J. ;
Wang, Q. ;
Niu, Y. ;
Fan, B. ;
Liu, X. ;
Zhang, S. ;
Sun, A. ;
Zou, Y. .
HEART, 2006, 92 (12) :1764-1767
[9]   Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study [J].
Gyoengyoesi, Mariann ;
Lang, Irene ;
Dettke, Markus ;
Beran, Gilbert ;
Graf, Senta ;
Sochor, Heinz ;
Nyolczas, Noemi ;
Charwat, Silvia ;
Hemetsberger, Rayyan ;
Christ, Guenter ;
Edes, Istvan ;
Balogh, Laszlo ;
Krause, Korff Thomas ;
Jaquet, Kai ;
Kuck, Karl-Heinz ;
Benedek, Imre ;
Hintea, Theodora ;
Kiss, Robert ;
Preda, Istvan ;
Kotevski, Vladimir ;
Pejkov, Hristo ;
Zamini, Sholeh ;
Khorsand, Aliasghar ;
Sodeck, Gottfried ;
Kaider, Alexandra ;
Maurer, Gerald ;
Glogar, Dietmar .
NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE, 2009, 6 (01) :70-81
[10]   Monitoring of bone marrow cell homing into the infarcted human myocardium [J].
Hofmann, M ;
Wollert, KC ;
Meyer, GP ;
Menke, A ;
Arseniev, L ;
Hertenstein, B ;
Ganser, A ;
Knapp, WH ;
Drexler, H .
CIRCULATION, 2005, 111 (17) :2198-2202