Augmenting Endogenous Wnt Signaling Improves Skin Wound Healing

Abstract

Wnt signaling is required for both the development and homeostasis of the skin, yet its contribution to skin wound repair remains controversial. By employing Axin2LacZ/+ reporter mice we evaluated the spatial and temporal distribution patterns of Wnt responsive cells, and found that the pattern of Wnt responsiveness varies with the hair cycle, and correlates with wound healing potential. Using Axin2LacZ/LacZ mice and an ear wound model, we demonstrate that amplified Wnt signaling leads to improved healing. Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2LacZ/LacZ mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing. Given the importance of Wnt signaling in the maintenance and repair of skin, liposomal Wnt3a may have widespread application in clinical practice.

The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

“…in the dermal fibroblasts during cutaneous wound healing. Although there are slight variations of activity levels with the wounds in other references (Gay et al, 2013;Whyte et al, 2013), these results are still correlated. Endothelin-1, a target of Wnt/-catenin pathway, was also specifically increased in the fibroblasts of CXXC5 / mouse wounds.…”

“…For efficient skin penetration, there are many methodologies, including PTD conjugation , liposomalization (Whyte et al, 2013), and use of penetration enhancers (Lan et al, 2014). Considering the skin penetration efficiency, we used PTD for efficient delivery and FITC for visualization.…”

Stem Cells in Skin Wound Healing: Are We There Yet?

“…Despite this limited knowledge, local stem cell mobilization 17,18 has been proposed as an answer to the low engraftment rate of transplanted exogenous stem cells. 19 Nonetheless, it is important to highlight that these mechanisms have been studied in rodents and that the translational settings toward humans might represent a long leap for a clinical situation.…”

PEGylated Liposomes Associate With Wnt3A Protein and Expand Putative Stem Cells in Human Bone Marrow Populations

“…As Wnt proteins carry fatty acid modifications which render them unstable in aqueous solution [26,27], liposome incorporation (for one member of the Wnt family, Wnt3A) has been shown to be an effective method of preserving both in vitro and in vivo stability and activity [28][29][30][31][32]. However, several challenges and unanswered questions remain.…”

“…However, several challenges and unanswered questions remain. Inclusion of PEGylated lipids has been shown to abolish the activity of current liposome preparations [30], restricting their use to local application or injection [29,32]. Local injection may disturb the hematoma or fracture callus (the integrity of which is important in healing) and in many cases may be difficult (requiring radiological expertise), painful and increase the risk of infection, therefore in many cases systemic delivery may be advantageous.…”