Arteriogenesis in murine adipose tissue is contingent on CD68⁺/CD206⁺ macrophages

Abstract

Objective The surgical transfer of skin, fat, and/or muscle from a donor site to a recipient site within the same patient, is a widely performed procedure in reconstructive surgeries. A surgical pre-treatment strategy that is intended to increase perfusion in the flap, termed “flap delay”, is a commonly employed technique by plastic surgeons prior to flap transplantation. Here, we explored whether CD68+/CD206+ macrophages are required for arteriogenesis within the flap by performing gain-of-function and loss-of-function studies in a previously published flap delay murine model. Methods and Results Local injection of M2-polarized macrophages into the flap resulted in an increase in collateral vessel diameter. Application of a thin biomaterial film loaded with a pharmacological agent (FTY720), which has been previously shown to recruit CD68+/CD206+ macrophages to remodeling tissue, increased CD68+/CD206+ cell recruitment and collateral vessel enlargement. Conversely, when local macrophage populations were depleted within the inguinal fat pad via clodronate liposome delivery, we observed fewer CD68+ cells accompanied by diminished collateral vessel enlargement. Conclusions Our study underscores the importance of macrophages during microvascular adaptations that are induced by flap delay. These studies suggest a mechanism for a translatable therapeutic target that may be used to enhance the clinical flap delay procedure.

PPAR‐γ regulates the polarization of M2 macrophages to improve the microenvironment for autologous fat grafting

“…Macrophage polarization has a complex and multidimensional effect on changes in the microenvironment in AFG. First, macrophages affect the vascularization process, 54 thus affecting the survival and regeneration of adipocytes. Studies have shown that in a hypoxic environment, M2 macrophages can produce proteases such as MMP‐2 and MMP‐9, which can cause the hydrolysis of ECM, induce the invasion and fusion of nearby tip cells, and form neovasculature 55 .…”

The Protective Effect of Epimysium Preservation and FTY720 on Functional Gracilis Transfer: Experimental Rabbit Study

“…In the muscle injury model of rats, FTY720 can effectively reduce the local in ammatory cell in ltration, and make macrophages enter M2 phase ahead of time, reduce the severity of muscle injury, improve muscle regeneration and reduce muscle brosis [30,31]. Some studies showed that the application of an FTY720-loaded lm increased M2 monocyte/macrophage recruitment, as well as arteriogenesis in ischemic skeletal muscle [32][33][34]. FTY720 can signi cantly reduce the degree of myocardial brosis and reduce the mortality of experimental animals in the model of myocardial ischemia-reperfusion [35].…”

The Immunosuppressant Fingolimod (FTY720) for the Treatment of Mechanical Force-Induced Abnormal Scars

“…This systemic change may be a secondary response to immunosuppression. FTY720 has previously been reported to increase the numbers of M2 macrophages in remodeling tissues [45,46]. Qin et al reported that FTY720 is effective in reducing brain inflammation by directing microglia after chronic cerebral hypoperfusion to M2 polarization [47].…”