Copyright © 2004, European Society of Cardiology
Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice
aCardiac Surgery, University of Rostock, Rostock, Germany
bInstitute of Biomedical Engineering, Rostock, Germany
cHematology and Oncology, University of Rostock, Germany
dInstitute of Immunology, University Rostock, Germany
eVita 34, Leipzig, Germany
* Corresponding author. Klinik für Herzchirurgie, Universität Rostock, Schillingallee 35, 18057 Rostock, Germany. Tel.: +49 381 494 6101; fax: +49 381 494 6102. Email address: christof.stamm{at}med.uni-rostock.de
Objective: We tested the hypothesis that intravenously administered human umbilical cord blood (hUCB) cells contribute to repair processes following myocardial infarction.
Methods: hUCB mononuclear cells containing 0.11% to 1.1% CD34+ cells were injected in the tail vein of NOD/scid mice that had (MI+) or had not (MI–) previously undergone ligation of the left anterior coronary artery (LAD). Homing to bone marrow and solid organs was determined by polymerase chain reaction (PCR) for human DNA (hDNA) using human-specific primers of Locus D7Z1. Immunostaining was used for phenotypic analysis, and capillary density as well as myocardial scar formation was assessed. Moreover, expression of stromal cell-derived factor-1 (SDF-1) was studied in infarcted and in normal hearts.
Results: hDNA was detected in marrow, spleen, and liver of both MI+ and MI– mice 24 h, 1 week, and 3 weeks after cell injection. In the heart, however, hDNA was detected in 10 of 19 MI+ mice but in none of the MI– mice (p=0.002). Infarct size was smaller in cell-treated MI+ mice than in untreated MI+ hearts (38.7 versus 47.8%, P<0.05), and there was also less collagen deposition. In cell-treated MI+ mice, capillary density in the infarct border zone was approximately 20% higher (p=0.03), and clusters of hUCB-derived cells were detected in the perivascular interstitium. Occasionally, chimeric capillaries composed of human and mouse endothelial cells were found, but the vast majority of neo-vessels appeared to consist of mouse cells only. Up to 70% of the cord blood-derived cells in the heart were CD45+. There was no evidence of cardiomyocyte differentiation as determined by co-localization of HNA or HLA-I with GATA-4 or Connexin 43. In infarcted myocardium, expression of SDF-1 mRNA was approximately 7-fold higher than in normal hearts.
Conclusions: hUCB cells migrate to infarcted, not to normal myocardium, where they engraft, participate in neoangiogenesis, and beneficially influence remodelling processes. Cord blood cells may hence be useful for cell therapy of ischemic heart disease.
KEYWORDS Cord blood; Cell therapy; Angiogenesis; Infarction; Transplantation
Time for primary review 19 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. J. Hohensinner, C. Kaun, K. Rychli, A. Niessner, S. Pfaffenberger, G. Rega, A. Furnkranz, P. Uhrin, J. Zaujec, T. Afonyushkin, et al. The inflammatory mediator oncostatin M induces stromal derived factor-1 in human adult cardiac cells FASEB J, March 1, 2009; 23(3): 774 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Reinecke, E. Minami, W.-Z. Zhu, and M. A. Laflamme Cardiogenic Differentiation and Transdifferentiation of Progenitor Cells Circ. Res., November 7, 2008; 103(10): 1058 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Cho, S.-H. Moon, S.-H. Lee, S.-W. Kang, J. Kim, J. M. Lim, H.-S. Kim, B.-S. Kim, and H. M. Chung Improvement of Postnatal Neovascularization by Human Embryonic Stem Cell-Derived Endothelial-Like Cell Transplantation in a Mouse Model of Hindlimb Ischemia Circulation, November 20, 2007; 116(21): 2409 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Cho, I.-K. Kim, S. H. Bhang, B. Joung, Y. J. Kim, K. J. Yoo, Y.-S. Yang, C. Y. Choi, and B.-S. Kim Combined therapy with human cord blood cell transplantation and basic fibroblast growth factor delivery for treatment of myocardial infarction Eur J Heart Fail, October 1, 2007; 9(10): 974 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Hu, S. Dai, W.-J. Wu, W. Tan, X. Zhu, J. Mu, Y. Guo, R. Bolli, and G. Rokosh Stromal Cell Derived Factor-1{alpha} Confers Protection Against Myocardial Ischemia/Reperfusion Injury: Role of the Cardiac Stromal Cell Derived Factor-1{alpha} CXCR4 Axis Circulation, August 7, 2007; 116(6): 654 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. W. van Laake, S. van den Driesche, S. Post, A. Feijen, M. A. Jansen, M. H. Driessens, J. J. Mager, R. J. Snijder, C. J. J. Westermann, P. A. Doevendans, et al. Endoglin Has a Crucial Role in Blood Cell-Mediated Vascular Repair Circulation, November 21, 2006; 114(21): 2288 - 2297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Boyle, S. P. Schulman, and J. M. Hare Stem Cell Therapy for Cardiac Repair: Ready for the Next Step Circulation, July 25, 2006; 114(4): 339 - 352. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ma, Y. Ladilov, J. M. Moebius, L. Ong, C. Piechaczek, A. David, A. Kaminski, Y.-H. Choi, W. Li, D. Egger, et al. Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: Bone marrow vs. cord blood-derived cells Cardiovasc Res, July 1, 2006; 71(1): 158 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Awad, E. I. Dedkov, C. Jiao, S. Bloomer, R. J. Tomanek, and G. C. Schatteman Differential Healing Activities of CD34+ and CD14+ Endothelial Cell Progenitors Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 758 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Friedrich and M. Bohm Human umbilical cord blood cells and myocardial infarction: Novel ways to treat an old problem Cardiovasc Res, April 1, 2005; 66(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Tse and M. J. Laughlin Umbilical Cord Blood Transplantation: A New Alternative Option Hematology, January 1, 2005; 2005(1): 377 - 383. [Abstract] [Full Text] [PDF]
|
|