The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism

Abstract

ObjectivesThe aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model.MethodsMSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium.A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.ResultsThe cell count in the low-dose G-CSF medium was significantly higher than that in the control medium. The differentiation potential of MSCs was preserved after culturing them with G-CSF.Macroscopically, defects were filled and surfaces were smoother in the G-CSF groups than in the control group at four weeks. At 12 weeks, the quality of repaired cartilage improved further, and defects were almost completely filled in all groups. Microscopically, at four weeks, defects were partially filled with hyaline-like cartilage in the G-CSF groups. At 12 weeks, defects were repaired with hyaline-like cartilage in all groups.ConclusionsG-CSF promoted proliferation of MSCs in vitro. The systemic administration of G-CSF promoted the repair of damaged cartilage possibly through increasing the number of MSCs in a rabbit model.Cite this article: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. Bone Joint Res 2017;6:123–131. DOI: 10.1302/2046-3758.63.BJR-2016-0083.

Deciphering the Association of Cytokines, Chemokines, and Growth Factors in Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Using an ex vivo Osteochondral Culture System

“…It was also demonstrated to increase MSCs at the microfracture sites of a full-thickness chondral defect and thereby enhance cartilage repair in vivo in New Zealand white rabbits (Truong et al, 2017). GM-CSF promotes repair of the damaged cartilage by stimulating proliferation of MSCs (Okano et al, 2014;Sasaki et al, 2017) whereas EGF binding to its receptor activates EGFR-mediated signaling which is crucial for the maintenance of chondrocyte number by protecting them from undergoing apoptosis during OA progression (Zhang et al, 2014;Jia et al, 2016). HGF was upregulated in OA cartilage and synovial fluids of patients compared to healthy subjects (Abed et al, 2015).…”

Human Amniotic Mesenchymal Stem Cell Sheets Encapsulating Cartilage Particles Facilitate Repair of Rabbit Osteochondral Defects

“…This environment of cytokines may promote cell survival, migration, and differentiation. 8,32,36,45 Studies have shown that activation of FGF 43 and TGF-β 49 signaling pathways promote the repair of cartilage defects and the synthesis of extracellular matrix. This study confirmed the ability of the implanted hAMSCs to survive and differentiate into chondrocytes.…”

Articular Cartilage Regeneration in Osteoarthritis

“…Synthetic growth factors recombinant polypeptides are: transforming growth factor beta (TGF-β1), bone morphogenetic protein (BMP)-2 and BMP-7 (also known as osteogenic protein-1, OP-1; each of the TGF-β superfamily); insulin-like growth factor-I (IGF-1); fibroblast growth factor-2 (FGF-2) and fibroblast growth factor-18 (FGF-18) of the fibroblast growth factor family and platelet-derived growth factor (PDGF) [80]. Several recent reports have indicated that the granulocyte-colony stimulating factor (G-CSF) serves not only as a growth factor for haematopoietic stem cells, but is also able to promote MSC mobilisation to both bone marrow and peripheral blood [81]. This discovery has been put into practice by Garay-Mendoza and colleagues, who conducted a prospective open-label, phase I/II clinical trial in patients with knee OA.…”