Granulocyte macrophage - colony stimulating factor (GM-CSF) significantly enhances articular cartilage repair potential by microfracture

Abstract

OBJECTIVE: To investigate whether granulocyte macrophage-colony stimulating factor (GM-CSF) can be used to increase the number of mesenchymal stem cells (MSCs) in blood clots formed by microfracture arthroplasty (MFX) and whether it can improve the therapeutic outcome for cartilage repair. METHODS: Thirty-six New Zealand white rabbits were divided into four groups: (1) control, (2) GM-CSF, (3) MFX, and (4) GM-CSF + MFX. GM-CSF was administrated intravenously (IV) at 10 mug/kg body weight 20 min before the MFX surgery. The repaired tissues were retrieved and examined by histological observation, quantitative assessment, and biochemical assays at 4, 8, and 12 weeks after treatment. The number of MSCs was measured in the blood clots by the colony forming unit-fibroblast (CFU-F) assay. The kinetic profile and distribution of GM-CSF in vivo was also evaluated by near-Infrared (NIR) fluorescence imaging and enzyme-linked immune sorbent assay. RESULTS: In the histological observations and chemical assays examined at 4, 8, and 12 weeks, the MFX after GM-CSF administration showed better cartilage repair than the one without GM-CSF. The CFU-F assay showed a significantly larger amount of MSCs present in the blood clots of the GM-CSF + MFX group than in the blood clots of the other groups. The blood concentration of GM-CSF peaked at 10 min and decreased back to almost the initial level after a couple of hours. GM-CSF was distributed in many organs including the bone marrow but was not observed clearly in the joint cavity. CONCLUSION: Intravenous administration of GM-CSF together with MFX could be a promising therapeutic protocol to enhance the repair of cartilage defects.