The systemic influence of platelet-derived growth factors on bone marrow mesenchymal stem cells in fracture patients

BMC Medicine

Elena Jones²  Dennis McGonagle²  Sally A Boxall²  Peter V Giannoudis¹  Hiang Boon Tan¹ 

[1]Academic Unit of Trauma and Orthopaedics, Leeds General Infirmary, Great George St, Leeds LS1 3EX, UK

[2]Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Room 5.24, Clinical Sciences Building, Leeds LS9 7TF, UK

关键词: Platelets;    PDGF;    Bone marrow;    MSCs;    Mesenchymal stem cells;   

Others  :  1109846
DOI  :  10.1186/s12916-014-0202-6

 received in 2014-08-08, accepted in 2014-10-03,  发布年份 2015

【 摘 要 】

Background

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.

Methods

ICBM 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.

Results

Regardless 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.

Conclusions

Platelet 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.

【 授权许可】

   
2015 Tan et al.; licensee BioMed Central.

【 图 表 】

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