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Human Cord Blood Cells and Myocardial Infarction: Effect of Dose and Route of Administration on Infarct Size

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There is no consensus regarding the optimal dose of stem cells or the optimal route of administration for the treatment of acute myocardial infarction. Bone marrow cells, containing hematopoietic and mesenchymal stem cells, in doses of 0.5 × 106 to >30 × 106 have been directly injected into the myocardium or into coronary arteries or infused intravenously in subjects with myocardial infarctions to reduce infarct size and improve heart function. Therefore, we determined the specific effects of different doses of human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic and mesenchymal stem cells, on infarct size. In order to determine the optimal technique for stem cell administration, HUCBC were injected directly into the myocardium (IM), or into the LV cavity with the ascending aorta transiently clamped to facilitate coronary artery perfusion (IA), or injected intravenously (IV) in rats 1–2 h after the left anterior coronary artery was permanently ligated. Immune suppressive therapy was not given to any rat. One month later, the infarct size in control rat hearts treated with only Isolyte averaged 23.7 ± 1.7% of the LV muscle area. Intramyocardial injection of HUCBC reduced the infarct size by 71% with 0.5 × 106 HUCBC and by 93% with 4 × 106 HUCBC in comparison with the controls (p < 0.001). Intracoronary injection reduced the infarction size by 47% with 0.5 × 106 HUCBC and by 80% with 4 × 106 HUCBC (p < 0.001), and IV HUCBC reduced infarct size by 51% with 0.5 × 106 and by 75–77% with 16–32 million HUCBC (p < 0.001) in comparison with control hearts. With 4 × 106 HUCBC, infarction size was 65% smaller with IM HUCBC than with IA HUCBC and 78% smaller than with IV HUCBC (p < 0.05). Nevertheless, IM, IA, and IV HUCBC all produced significant reductions in infarct size in comparison with Isolyte-treated infarcted hearts without requirements for host immune suppression. The present experiments demonstrate that the optimal dose of HUCBC for reduction of infarct size in the rat is 4 × 106 IM, 4 × 106 IA, and 16 × 106 IV, and that the IM injection of HUCBC is the most effective technique for reduction in infarct size.

Keywords: Cell therapy; Coronary artery disease; Myocardial infarction; Stem cells

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368907783338299

Affiliations: 1: Department of Medicine of the James A. Haley VA Hospital, University of South Florida College of Medicine, Tampa, FL, USA 2: Saneron CCEL Therapeutics, Inc., Tampa, FL, USA 3: Department of Neurosurgery, Center of Excellence for Aging and Brain Repair, University of South Florida College of Medicine, Tampa, FL, USA 4: †Department of Pathology of the James A. Haley VA Hospital, University of South Florida College of Medicine, Tampa, FL, USA

Publication date: September 1, 2007

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.



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