Abstract
BackgroundFracture healing is a complex process regulated by a variety of cells and signalling molecules which act both locally and systemically. The aim of this study was to investigate potential changes in patients’ mesenchymal stem cells (MSCs) in the iliac crest (IC) bone marrow (BM) and in peripheral blood (PB) in relation to the severity of trauma and to correlate them with systemic changes reflective of inflammatory and platelet responses following fracture.MethodsICBM samples were aspirated from two trauma groups: isolated trauma and polytrauma (n = 8 and 18, respectively) at two time-points post-fracture and from non-trauma controls (n = 7). Matched PB was collected every other day for a minimum of 14 days. BM MSCs were enumerated using colony forming-fibroblast (CFU-F) assay and flow cytometry for the CD45-CD271+ phenotype.ResultsRegardless of the severity of trauma, no significant increase or decrease in BM MSCs was observed following fracture and MSCs were not mobilised into PB. However, direct positive correlations were observed between changes in the numbers of aspirated BM MSCs and time-matched changes in their serum PDGF-AA and -BB. In vitro, patients’ serum induced MSC proliferation in a manner reflecting changes in PDGFs. PDGF receptors CD140a and CD140b were expressed on native CD45-CD271+ BM MSCs (average 12% and 64%, respectively) and changed over time in direct relationship with platelets/PDGFs.ConclusionsPlatelet lysates and other platelet-derived products are used to expand MSCs ex vivo. This study demonstrates that endogenous PDGFs can influence MSC responses in vivo. This indicates a highly dynamic, rather than static, MSC nature in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0202-6) contains supplementary material, which is available to authorized users.
Highlights
Fracture healing is a complex process regulated by a variety of cells and signalling molecules which act both locally and systemically
We hypothesised that powerful signalling molecules, such as the plateletderived growth factors (PDGFs) released into circulation after fracture, may affect mesenchymal stem cells (MSCs) at sites remote to the initial injury. To address this hypothesis we investigated MSCs in the iliac crest (IC) bone marrow (BM) aspirates and peripheral blood (PB) of patients suffering differing severities of injury and correlated MSC changes with patient- and time-matched changes in serum PDGFs as well as total white cell and platelet counts
Patient’s MSCs express PDGF receptors and modulate their expression in response to changes in platelets To investigate other potential changes in BM MSCs in response to endogenous PDGFs, we investigated the expression of PDGF receptors α and β (CD140a and CD140b) on their surface [32] and analysed BM MSCs based on their native CD45-CD271+ phenotype, as previously reported [21,22,24,32,33]
Summary
Fracture healing is a complex process regulated by a variety of cells and signalling molecules which act both locally and systemically. The aim of this study was to investigate potential changes in patients’ mesenchymal stem cells (MSCs) in the iliac crest (IC) bone marrow (BM) and in peripheral blood (PB) in relation to the severity of trauma and to correlate them with systemic changes reflective of inflammatory and platelet responses following fracture. Fracture healing is a highly co-ordinated physiological process with initial haematoma formation followed by an acute inflammatory response leading to an osteogenic repair phase, all tightly regulated by a variety of cytokines and other mediators and cells [1]. The later osteogenic phase is mediated locally via the recruitment of mesenchymal stem cells (MSCs) from adjacent periosteum, cortical bone and bone marrow [6].
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