Hematopoietic stem cells do not repair the infarcted mouse heart

被引:76
作者
Deten, A
Volz, HC
Clamors, S
Leiblein, S
Briest, W
Marx, G
Zimmer, HG
机构
[1] Univ Leipzig, Carl Ludwig Inst Physiol, D-04103 Leipzig, Germany
[2] Univ Leipzig, Dept Hematol, D-04103 Leipzig, Germany
关键词
infarction; stem cells; cell therapy; hemodynamics; heart failure;
D O I
10.1016/j.cardiores.2004.11.009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Recent reports suggest that hematopoietic stem cells (HSC) can transdifferentiate into cardiomyoctes and contribute to myocardial regeneration after injury. This concept has recently been challenged by studies in which bone-marrow (BM)-derived cells do not acquire a cardiac phenotype after direct injection into ischemic myocardium. Methods: In this study, we analyzed the effect of increased circulating adult BM cells by stimulation with stem cell factor (SCF; 200 mug/kg/d for 7 days) and granulocyte-colony stimulating factor (G-CSF, 50 mug/kg/d for 7 days) or by peripheral delivery of isolated adult BM cells on morphological and hemodynamic parameters of mouse hearts 6 weeks after induction of chronic myocardial infarction (MI). All animals were splenectomized to prevent sequestration of BM cells 2 weeks prior to the induction of MI. Cytokine treatment was initiated either 3 days prior to or 6 h after MI. Isolated, either whole or by magnetic beads lineage-depleted BM cells were injected via a tail vein 6 It after MI. Results: Left and right ventricular (LV and RV) function revealed no improvement in any treatment group when compared to untreated MI animals at baseline resting conditions as well as after stimulation with norepinephrine (NE; 1, 5, 10, 25, 50, and 100 ng bolus i.v. in 10 mul each) as measured by catherization with ultraminiature 1.4 F tip pressure transducers 6 weeks after MI. Moreover, there was no sign of myocardial regeneration in histological or gene expression analyses. Conclusion: Mobilization or i.v. injection of BM cells do not have a measurable effect on cardiac regeneration. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:52 / 63
页数:12
相关论文
共 30 条
  • [1] Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes
    Alvarez-Dolado, M
    Pardal, R
    Garcia-Vardugo, JM
    Fike, JR
    Lee, HO
    Pfeffer, K
    Lois, C
    Morrison, SJ
    Alvarez-Buylla, A
    [J]. NATURE, 2003, 425 (6961) : 968 - 973
  • [2] Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction -: (TOPCARE-AMI)
    Assmus, B
    Schächinger, V
    Teupe, C
    Britten, M
    Lehmann, R
    Döbert, N
    Grünwald, F
    Aicher, A
    Urbich, C
    Martin, H
    Hoelzer, D
    Dimmeler, S
    Zeiher, AM
    [J]. CIRCULATION, 2002, 106 (24) : 3009 - 3017
  • [3] Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium
    Balsam, LB
    Wagers, AJ
    Christensen, JL
    Kofidis, T
    Weissman, IL
    Robbins, RC
    [J]. NATURE, 2004, 428 (6983) : 668 - 673
  • [4] Evidence that human cardiac myocytes divide after myocardial infarction (Publication with Expression of Concern. See vol. 379, pg. 1870, 2018)
    Beltrami, AP
    Urbanek, K
    Kajstura, J
    Yan, SM
    Finato, N
    Bussani, R
    Nadal-Ginard, B
    Silvestri, F
    Leri, A
    Beltrami, CA
    Anversa, P
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (23) : 1750 - 1757
  • [5] Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice
    Bittner, RE
    Schöfer, C
    Weipoltshammer, K
    Ivanova, S
    Streubel, B
    Hauser, E
    Freilinger, M
    Höger, H
    Elbe-Bürger, A
    Wachtler, F
    [J]. ANATOMY AND EMBRYOLOGY, 1999, 199 (05): : 391 - 396
  • [6] BODINE DM, 1994, BLOOD, V84, P1482
  • [7] Bone marrow-derived cardiomyocytes are present in adult human heart - A study of gender-mismatched bone marrow transplantation patients
    Deb, A
    Wang, SH
    Skelding, KA
    Miller, D
    Simper, D
    Caplice, NM
    [J]. CIRCULATION, 2003, 107 (09) : 1247 - 1249
  • [8] Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats
    Deten, A
    Hölzl, A
    Leicht, M
    Barth, W
    Zimmer, HG
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2001, 33 (06) : 1191 - 1207
  • [9] Heart function and cytokine expression is similar in mice and rats after myocardial infarction but differences occur in TNFα expression
    Deten, A
    Zimmer, HG
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2002, 445 (02): : 289 - 296
  • [10] Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats
    Deten, A
    Volz, HC
    Briest, W
    Zimmer, HG
    [J]. CARDIOVASCULAR RESEARCH, 2002, 55 (02) : 329 - 340