Mobilization of CD34+-Progenitor Cells in Patients with Severe Trauma

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.

CD34+ cells seeded in collagen scaffolds promote bone formation in a mouse calvarial defect model

“…Additionally, there have been other studies investigating other aspects of CD34 + cells. Ritz et al found that of CD34 + cells were significantly increased in patients with multiple trauma. Other experimental animal studies, have found translocation of CD34 + cells from the bone marrow to the peripheral blood .…”

“…To date, most studies have used HUVECs or EPCs as their preferred endothelial cell type. However, there has been increasing interest in substituting CD34 + cells for this purpose . Matsumoto et al first described the positive effect of CD34 + cells on bone healing.…”

“…The phagocytosis of low‐density lipoprotein (LDL) and the specific binding of Ulex europeus lectin to endothelial membrane receptors were investigated in purified CD34+ cell cultures by double staining with DiI‐ac‐LDL (acetylated LDL) and lectin as described by Ritz . CD34+ cells were purified as described above, plated on fibronectin‐coated 24‐well plates and allowed to adhere for 24 h prior to the staining procedure.…”

Trauma and Stem Cells: Biology and Potential Therapeutic Implications

“…Ritz et al [33] studied the peripheral blood of 20 severely traumatised patients and demonstrated elevated numbers of CD34+ cells in circulation compared to control. Serial blood collections found progressively increasing numbers of CD34+ colony forming units (CFU) from admission until Day 7 compared to control.…”

“…Serial blood collections found progressively increasing numbers of CD34+ colony forming units (CFU) from admission until Day 7 compared to control. These CD34+ cells are believed to be haematopoietic cells or endothelial progenitors with pro-angiogenic capacity [33], demonstrating again a stem cell migratory response to trauma. …”