Abstract
Objective
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.
Methods
Trauma patients with lower extremity fractures (n=18, age 21–64 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 ELISA. Iliac crest (BM) aspirate (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=18), which reached up to 4-fold on day 7. In 12 out of 18 patients recruited for CFU-F study, an increase in iliac crest BM CFU-F/ml of aspirate was observed, reaching an average 10-fold post-fracture (range days 3 to day 9). In 15 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 (r=0.55, p< 0.05).
Discussion and 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. This data therefore enable a more comprehensive understanding of MSC dynamics in response to trauma and can inform the design of a clinical trial aimed to optimise the location and timing of BM harvest for use in bone regeneration following fracture.
