Decreased pool of mesenchymal stem cells is associated with altered chemokines serum levels in atrophic nonunion fractures

• Published in: Bone (New York, N.Y.) Vol. 53; no. 2; pp. 391 - 398
• Main Authors: Mathieu, Myrielle, Rigutto, Sabrina, Ingels, Aude, Spruyt, Delphine, Stricwant, Nadia, Kharroubi, Ilham, Albarani, Valentina, Jayankura, Marc, Rasschaert, Joanne, Bastianelli, Enrico, Gangji, Valérie
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.04.2013; Elsevier
• Subjects: Adult; Biological and medical sciences; Bone healing; Cells, Cultured; Chemokines; Chemokines - blood; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelial progenitor cells; Female; Fractures, Ununited - blood; Fractures, Ununited - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Injuries of the limb. Injuries of the spine; Male; Medical sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Nonunion; Orthopedics; Traumas. Diseases due to physical agents; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Young Adult; Nonunion; Bone healing; Chemokines; Endothelial progenitor cells; Mesenchymal stem cells; Pseudoarthrosis; Endothelial cell; Stem cell; Diseases of the osteoarticular system; Fracture; Mesenchymal cell; Trauma; Chemokine; Morphology; Serum; Bone; Cicatrization; Progenitor cell
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2013.01.005

Abstract Nonunion fractures can cause severe dysfunction and are often difficult to treat mainly due to a poor understanding of their physiopathology. Although many aspects of impaired fracture healing have been extensively studied, little is known about the cellular and molecular mechanisms leading to atrophic nonunion. Therefore, the aim of the present study was to assess the pools and biological functions of bone marrow-derived mesenchymal stem cells (hMSCs) and circulating endothelial progenitor cells (EPCs) in atrophic nonunion patients compared to healthy subjects, and the systemic levels of growth factors involved in the recruitment, proliferation and differentiation of these cells. In nonunions, the pool of hMSCs was decreased and their proliferation delayed. However, once committed, hMSCs from nonunions were able to proliferate, differentiate into osteoblastic cells and mineralize in vitro as efficiently as hMSCs from healthy subjects. In parallel, we found altered serum levels of chemokines and growth factors involved in the chemotaxis and proliferation of hMSCs such as leptin, interleukin-6 (IL-6) and its soluble receptor, platelet-derived growth factor-BB (PDGF-BB), stem cell factor (SCF) and insulin-like growth factor-1 (IGF-1). Moreover, we showed that the number of EPCs and their regulating growth factors were not affected in nonunion patients. If nonunion is generally attributed to a vascular defect, our results also support a role for a systemic mesenchymal and osteogenic cell pool defect that might be related to alterations in systemic levels of factors implicated in their chemotaxis and proliferation.