Macrophages: A review of their role in wound healing and their therapeutic use. Snyder Robert J,Lantis John,Kirsner Robert S,Shah Vivek,Molyneaux Michael,Carter Marissa J Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society Macrophages are mononuclear phagocytes established during embryogenesis and derived from the yolk sac or the fetal liver but also recruited from the blood and bone marrow under proliferative inflammatory conditions (such as tissue repair). Most importantly, they take on distinct phenotypes and functions crucial to healing upon localization in the wound. The objective of this review is to summarize recent findings in regard to the cellular mechanisms of macrophages and chronic wounds. Advances in the potential use of macrophage therapy have arisen based, in part, on the fact that early recruitment of macrophages is critical to wound healing. Higher quality evidence is needed to support the use of macrophage therapy for chronic wound types, as is a better understanding of the signaling related to macrophage polarization, activation of macrophages, and their effect of mechanisms of repair. An evaluation of the currently available research on mechanism of action may lead to a better understanding of the signaling processes of the many macrophage phenotypes, as well as their roles and outcomes in wound healing, which could then guide the development and eventual widespread use of macrophage therapies. 10.1111/wrr.12444

Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing model. Clayton Zoë E,Tan Richard P,Miravet Maria M,Lennartsson Katarina,Cooke John P,Bursill Christina A,Wise Steven G,Patel Sanjay Bioscience reports Chronic wounds are a major complication in patients with cardiovascular diseases. Cell therapies have shown potential to stimulate wound healing, but clinical trials using adult stem cells have been tempered by limited numbers of cells and invasive procurement procedures. Induced pluripotent stem cells (iPSCs) have several advantages of other cell types, for example they can be generated in abundance from patients' somatic cells (autologous) or those from a matched donor. iPSCs can be efficiently differentiated to functional endothelial cells (iPSC-ECs). Here, we used a murine excisional wound model to test the pro-angiogenic properties of iPSC-ECs in wound healing. Two full-thickness wounds were made on the dorsum of NOD-SCID mice and splinted. iPSC-ECs (5 × 10) were topically applied to one wound, with the other serving as a control. Treatment with iPSC-ECs significantly increased wound perfusion and accelerated wound closure. Expression of endothelial cell (EC) surface marker, platelet endothelial cell adhesion molecule (PECAM-1) (CD31), and pro-angiogenic EC receptor, Tie1, mRNA was up-regulated in iPSC-EC treated wounds at 7 days post-wounding. Histological analysis of wound sections showed increased capillary density in iPSC-EC wounds at days 7 and 14 post-wounding, and increased collagen content at day 14. Anti-GFP fluorescence confirmed presence of iPSC-ECs in the wounds. Bioluminescent imaging (BLI) showed progressive decline of iPSC-ECs over time, suggesting that iPSC-ECs are acting primarily through short-term paracrine effects. These results highlight the pro-regenerative effects of iPSC-ECs and demonstrate that they are a promising potential therapy for intractable wounds. 10.1042/BSR20180563

Caffeic acid phenethyl ester promotes wound healing of mice pressure ulcers affecting NF-κB, NOS2 and NRF2 expression. Romana-Souza Bruna,Dos Santos Jeanine Salles,Monte-Alto-Costa Andréa Life sciences AIMS:In pressure ulcers, the synthesis of reactive oxygen species induced by ischemia and reperfusion leads to chronic inflammation and tissue damage, which impair the closure of these lesions. Caffeic acid phenethyl ester (CAPE), found in propolis, promotes cutaneous wound healing of acute lesions and severe burns. However, the effects of CAPE on wound healing of pressure ulcers have not been investigated. This study investigated the effects of CAPE administration in a murine model of pressure ulcers. MAIN METHODS:To induce pressure ulcers, two cycles of ischemia and reperfusion by external application of two magnetic plates were performed in the skin dorsum of mice. After the last cycle, animals were treated daily with CAPE or vehicle until they were euthanized. KEY FINDINGS:The nitric oxide synthesis, lipid peroxidation, macrophage migration, protein nuclear factor kappa B and nitric-oxide synthase-2 expression were increased 3 days after ulceration but decreased 7 days later, in pressure ulcers of the CAPE group compared to that of the control group. CAPE reduced the protein expression of nuclear factor-erythroid2-related factor 2 in pressure ulcers 3 days after ulceration, but increased 7 days later. Myofibroblast density was increased in the CAPE group 7 days after ulceration, but reduced 12 days later when compared to control group. In addition, CAPE promoted collagen deposition, re-epithelialization and wound closure of mice pressure ulcers 12 days after ulceration. SIGNIFICANCE:CAPE brings forward inflammatory response and oxidative damage involved in injury by ischemia and reperfusion, promoting dermal reconstruction and closure of pressure ulcers. 10.1016/j.lfs.2018.05.057