Junrong Cai1,2, Jingwei Feng1,2, Kaiyang Liu1,2, Shaolong Zhou1,2, Feng Lu1,2. 1. Guangzhou, Guangdong, People's Republic of China. 2. From the Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University.
Abstract
BACKGROUND: Fat grafting is a popular soft-tissue filler method; however, its results are variable and technique-dependent. Macrophages are present in fat grafts and closely associated with tissue regeneration. The authors hypothesized that activation/depletion of early macrophages in transferred fat improves/impairs fat graft survival. METHODS: Mouse inguinal fat (approximately 150 mg) was transferred autologously. Fat grafting was first performed without other manipulations to obtain baseline information. Then, liposome-encapsulated clodronate and macrophage-colony stimulating factor were used in a mouse fat grafting model for local macrophage depletion or activation. The authors examined the graft stromal vascular fraction by fluorescence-activated cell sorting at 1, 2, 4, and 12 weeks after transplantation in manipulation and control groups. Graft weight, vascularization, and secreted factors were also compared. RESULTS: Early depletion of macrophages resulted in incompetent angiogenesis, feeble Sca-1/CD45 stem cell recruitment, and eventually a poor retention rate (34 ± 6 mg versus control 84 ± 15 mg; p = 0.006), whereas up-regulated macrophages allowed better angiogenesis and survival (117 ± 12 mg versus control, 84 ± 15 mg; p = 0.043). CONCLUSIONS: In fat grafting, macrophages and their polarization initiated changes in the levels of dominant secreted factors and influenced blood-derived stem cell infiltration, indicating that macrophages were crucial for tissue revascularization. The macrophage manipulation models described here show that graft macrophage number can profoundly influence graft survival.
BACKGROUND: Fat grafting is a popular soft-tissue filler method; however, its results are variable and technique-dependent. Macrophages are present in fat grafts and closely associated with tissue regeneration. The authors hypothesized that activation/depletion of early macrophages in transferred fat improves/impairs fat graft survival. METHODS:Mouse inguinal fat (approximately 150 mg) was transferred autologously. Fat grafting was first performed without other manipulations to obtain baseline information. Then, liposome-encapsulated clodronate and macrophage-colony stimulating factor were used in a mouse fat grafting model for local macrophage depletion or activation. The authors examined the graft stromal vascular fraction by fluorescence-activated cell sorting at 1, 2, 4, and 12 weeks after transplantation in manipulation and control groups. Graft weight, vascularization, and secreted factors were also compared. RESULTS: Early depletion of macrophages resulted in incompetent angiogenesis, feeble Sca-1/CD45 stem cell recruitment, and eventually a poor retention rate (34 ± 6 mg versus control 84 ± 15 mg; p = 0.006), whereas up-regulated macrophages allowed better angiogenesis and survival (117 ± 12 mg versus control, 84 ± 15 mg; p = 0.043). CONCLUSIONS: In fat grafting, macrophages and their polarization initiated changes in the levels of dominant secreted factors and influenced blood-derived stem cell infiltration, indicating that macrophages were crucial for tissue revascularization. The macrophage manipulation models described here show that graft macrophage number can profoundly influence graft survival.