From Bone Marrow to Skin: The Transient Increase in Circulating Endothelial Progenitor Cells in Patients with Superficial and Full Thickness Burns Correlates with Surface Area and Depth of Injury and Circulating Chemokine Levels.

Preliminary studies from one other group have indicated that endothelial precursor cells (EPCs) can be detected in the peripheral blood of patients following thermal injury. It was reported in this study that these cells mobilise from the bone marrow into the circulation following this trauma, in order to contribute to wound healing at the site of burns injury. Here, we present a much more comprehensive study which is aimed at analysing the levels of EPCs over time in normal blood donor volunteers, and in umbilical cord blood donors and also at characterising the kinetics of the appearance and disappearance over time of such cells in the circulation of patients with superficial and severe full thickness burns. EPCs identified from surface expression patterns of CD45^lo, CD133⁺, CD144⁺, and VEGFR-2⁺ were quantified by four-colour flow cytometry. Interestingly, in normal healthy donors, individual EPC levels remained essentially constant over short periods of time (3–4 weeks). Burns patients, however, showed a rapid increase in circulating EPCs by these criteria, and this was maximal within the first 24 hours following burns injury, returning to basal levels by 72 hours. This represented a nine-fold increase (P=0.001) compared to control subjects (N=50, mean 51 ± 63 EPC/ml). In superficial burns, the rise in EPC levels was significantly related to the burnt surface area. Parallel to the mobilisation of EPCs, there was also elevation in plasma VEGF and CXCL12 levels as determined by ELISA. Maximal VEGF levels, for example, were detected within 24 hours and represented a six-fold increase (P=0.001) compared to controls (N=40, mean 28 ± 21 pg/ml), decreasing to basal levels by 72 hours. Similar results and trends were seen for CXCL12. Results demonstrate that there is an acute but transient increase in circulating EPCs following burns injuries. For the first time, they show that surface area and depth of injury affect the levels of circulating EPCs. These EPC levels correlate with levels of circulating chemokines, VEGF and CXCL12, in both burns patients and normal donors. By analysing chemokine levels in plasma, this latter finding may provide a simplified diagnostic test that will predict the levels of EPCs in the blood. Demonstrating a role for such EPCs in burns patients may also provide a therapeutic target and allow the development of improved strategies for treating and reducing the morbidity, scarring and mortality in patients who are often critically ill.