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Open Access Analyzing Migratory Properties of Human CD133+ Stem Cells In Vivo After Intraoperative Sternal Bone Marrow Isolation

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Abstract:

Human bone marrow stem cell populations have been applied for cardiac regeneration purposes within different clinical settings in the recent past. The migratory capacity of applied stem cell populations towards injured tissue, after undergoing specific peri-interventional harvesting and isolation procedures, represents a key factor limiting therapeutic efficacy. We therefore aimed at analyzing the migratory capacity of human cluster of differentiation (CD) 133+ bone marrow stem cells in vivo after intraoperative harvesting from the sternal bone marrow. Human CD133+ bone marrow stem cells were isolated from the sternal bone marrow of patients undergoing cardiac surgery at our institution. Migratory capacity towards stromal cell-derived factor-1α (SDF-1α) gradients was tested in vitro and in vivo by intravital fluoresecence microscopy, utilizing the cremaster muscle model in severe combined immunodeficient (SCID) mice and analyzing CD133+ cell interaction with the local endothelium. Furthermore, the role of a local inflammatory stimulus for CD133+ cell interaction with the endothelium was studied. In order to describe endothelial response upon chemokine stimulation laser scanning microscopy of histological cremaster muscle samples was performed. SDF-1α alone was capable to induce relevant early CD133+ cell interaction with the endothelium, indicated by the percentage of rolling CD133+ cells (45.9±1.8% in “SDF-1” vs. 17.7±2.7% in “control,” p<0.001) and the significantly reduced rolling velocity after SDF-1α treatment. Furthermore, SDF-1α induced firm endothelial adhesion of CD133+ cells in vivo. Firm endothelial adhesion, however, was significantly enhanced by additional inflammatory stimulation with tumor necrosis factor-α (TNF-α) (27.9±4.3 cells/mm2in “SDF-1 + TNF” vs. 2.2±1.1 cells/mm2 in “control,” p<0.001). CD133+ bone marrow stem cells exhibit sufficient in vivo homing towards SDF-1α gradients in an inflammatory microenvironment after undergoing standardized intraoperative harvesting and isolation from the sternal bone marrow.

Keywords: Bone marrow stem cell (BMSC); Cardiac surgery; Isolation; Migration; Stromal cell-derived factor-1α (SDF-1α)

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368912X657729

Affiliations: Reference and Translation Centre for Cardiac Stem Cell Therapy, Department for Cardiac Surgery, University of Rostock, Rostock, Germany

Publication date: September 11, 2013

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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