Effect of rhGM-CSF in promoting wound healing via macrophage immunomodulation

Background Recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is predominantly applied in hematologic disorder therapy. Emerging research suggests its efficacy in wound healing. This study aims to validate the effect and molecular mechanisms of rhGM-CSF on diabetic/non-diabetic wound healing. Methods Two full-thickness wounds were created on the backs of C57BL/6J mice. The caudal wounds were treated daily with topical rhGM-CSF (1.0 μg/cm2), while the cranial wounds received saline. Patients with diabetic lower extremity ulcers were randomized into rhGM-CSF intervention (2.0 μg/cm2 infiltration) and control group. The primary endpoint was the overall percentage area reduction by one month. The wound tissues were stained with HE and immunofluorescence. Western blot was performed to analyze macrophage subtypes. Results Topical administration of rhGM-CSF significantly accelerated wound healing in C57BL/6J mice with an average healing rate of 2.53±0.25 mm2/day. Increase in the capillary marker CD31 and the expression of vascular endothelial growth factor (VEGF)A was observed after rhGM-CSF intervention. The clinical trial included 48 subjects with comparable baseline characteristics between the rhGM-CSF (n=27) and control (n=21) groups. The rhGM-CSF group showed significantly greater overall percentage area reduction (97.7±8.9%) vs. controls (P<0.05). Mechanistically, the rhGM-CSF intervention resulted in a significant reduction in M1-type macrophages and an increase in M2-type macrophages, with M2a predominating at day 5 and M2d dominating at day 10 post-injury. Conclusions Our study suggested that topical administration of rhGM-CSF can promote the healing of both diabetic and non-diabetic wounds, which is partly attributed to promoting the transformation of macrophages to M2 subtype.