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.

Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs) are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 10⁶ green fluorescent protein (GFP)-expressing ASCs, aminoguanidine (AG) or phosphate-buffered saline (PBS). Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD) and malondialdehyde (MDA). Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE) levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

An alkali-induced egg white hydrogel achieved ultra-stretchability, self-healing and direct 3D printability for highly sensitive electronic sensor and humidity-responsive actuator fabrication.