Abstract
Circulating CD34+ progenitor cells () gained importance in the field of regenerative medicine due to their potential to home in on injury sites and differentiate into cells of both endothelial and osteogenic lineages. In this study, we analyzed the mobilization kinetics and the numbers of CD34+, CD31+, CD45+, and CD133+ cells in twenty polytrauma patients (n = 13 male, n = 7 female, mean age 46.5±17.2 years, mean injury severity score (ISS) 35.8±12.5 points). In addition, the endothelial differentiation capacity of enriched CD34+cells was assessed by analyzing DiI-ac-LDL/lectin uptake, the expression of endothelial markers, and the morphological characteristics of these cells in Matrigel and spheroid cultures. We found that on days 1, 3, and 7 after a major trauma, the number of CD34+cells increased from 6- up to 12-fold (p<0.0001) over the number of CD34+cells from a control population of healthy, age-matched volunteers. The numbers of CD31+ cells were consistently higher on days 1 (1.4-fold, p<0.01) and 7 (1.3-fold, p<0.01), whereas the numbers of CD133+ cell did not change during the time course of investigation. Expression of endothelial marker molecules in CD34+cells was significantly induced in the polytrauma patients. In addition, we show that the CD34+ cell levels in severely injured patients were not correlated with clinical parameters, such as the ISS score, the acute physiology and chronic health evaluation II score (APACHE II), as well as the sequential organ failure assessment score (SOFA-2). Our results clearly indicate that pro-angiogenic cells are systemically mobilized after polytrauma and that their numbers are sufficient for the development of novel therapeutic models in regenerative medicine.
Highlights
Musculoskeletal injuries are often accompanied by extensive vascular damage and local ischemia
There is a wealth of evidence that circulating bone marrow-derived endothelial progenitor cells (EPCs) represent an important fraction of endothelial cells, as they have been shown to be involved in the repair and regeneration of blood vessels in animal models of ischemic tissue damage and myocardial infarction [2,3,4]
Endothelial progenitor cells were first discovered by Asahara et al as CD34+ progenitor cells that derive from bone marrow [5]
Summary
Musculoskeletal injuries are often accompanied by extensive vascular damage and local ischemia. There is a wealth of evidence that circulating bone marrow-derived endothelial progenitor cells (EPCs) represent an important fraction of endothelial cells, as they have been shown to be involved in the repair and regeneration of blood vessels in animal models of ischemic tissue damage and myocardial infarction [2,3,4]. CD34+ cells represent a heterogeneous population of cells with subpopulations that have different genetic and biological characteristics. These cells express a broad range of diverse surface markers and contain progenitor cells that are capable of differentiating into both endothelial and osteogenic lineages under the appropriate stimulating conditions [6]. Clinical trials in the field of cardiovascular medicine provided evidence that enriched pools of autologous CD34+ cells can improve clinical outcome results when administered by intramyocardial, intravascular, or intramuscular injection and supported further clinical development of this treatment strategy [8,9]
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