Abstract
Background and objectives
Fracture healing represents a physiological process regulated by a variety of signalling molecules, growth factors and osteogenic progenitor cells. Bone healing following trauma is associated with increased serum concentrations of several pro-inflammatory and angiogenic growth factors1. Platelet-derived growth factor (PDGF) has been shown to stimulate mesenchymal stem cell (MSC) proliferation in vitro. However, the in vivo relationship between the levels of PDGF and the numbers of MSCs in humans has not yet been explored. The aim of this study was to investigate PDGF release in the peripheral circulation following trauma and to correlate it with the numbers of MSCs in iliac crest bone marrow (BM) aspirate and in peripheral blood.
Methods
Trauma patients with lower extremity fractures (n=12, age 18-63 years) were recruited prospectively. Peripheral blood was obtained on admission, and at 1, 3, 5 and 7 days following admission. The serum was collected and PDGF was measured using the enzyme-linked immuno-sorbent assay (ELISA) technique. Iliac crest (BM) aspirate (20ml) and peripheral blood (PB) (20ml) was obtained on days 0-9 following admission. MSCs were enumerated using standard colony-forming unit fibroblasts (CFU-F) assay.
Results
We observed a gradual increase in serum PDGF levels following fracture (r2=0.79, p=0.005, n=8), which reached up to 2-fold on day 7. In 5 out of 8 patients recruited for CFU-F study, an increase in iliac crest BM CFU-F per millilitre of aspirate was similarly observed, which reached an average 6-fold post-fracture (ranging from day 3 to day 9). No CFU-Fs were observed in PB at any time-point in all patients studied. In three patients, for which PDGF and CFU-F were measured in parallel, a strong positive correlation was observed between CFU-F numbers per millilitre of BM aspirate and circulating PDGF levels (r2=0.98, p<0.01).
Conclusion
Our data demonstrate, for the first time, that BM MSC pool in humans is not static and can be stimulated following trauma. This is not a result of mobilisation of MSCs into systemic circulation. Rather, MSC activation at remote sites, like iliac crest BM, can be due to systemic up-regulation of several cytokines and growth factors, including PDGF, in peripheral circulation.
