An Improved Humanized Mouse Model for Excisional Wound Healing Using Double Transgenic Mice

Abstract

Objective: Splinting full-thickness cutaneous wounds in mice has allowed for a humanized model of wound healing. Delineating the epithelial edge and assessing time to closure of these healing wounds via macroscopic visualization have remained a challenge. Approach: Double transgenic mice were created by crossbreeding K14-Cre and ROSA mT/mG reporter mice. Full-thickness excisional wounds were created in K14-Cre/ROSA mT/mG mice (n = 5) and imaged using both normal and fluorescent light on the day of surgery, and every other postoperative day (POD) until wound healing was complete. Ten blinded observers analyzed a series of images from a single representative healing wound, taken using normal or fluorescent light, to decide the POD when healing was complete. K14-Cre/ ROSA mT/mG mice (n = 4) were subsequently sacrificed at the four potential days of rated wound closure to accurately determine the histological point of wound closure using microscopic fluorescence imaging. Results: Average time to wound closure was rated significantly longer in the wound series images taken using normal light, compared with fluorescent light (mean POD 13.6 vs. 11.6, *p = 0.008). Fluorescence imaging of histological samples indicated that reepithelialization was complete at 12 days postwounding. Innovation: We describe a novel technique, using double transgenic mice K14-Cre/ROSA mT/mG and fluorescence imaging, to more accurately determine the healing time of wounds in mice upon macroscopic evaluation. Conclusion: The accuracy by which wound healing can be macroscopically determined in vivo in mouse models of wound healing is significantly enhanced using K14-Cre/ROSA mT/mG double transgenic mice and fluorescence imaging.

Electrospun PCL/PLA Scaffolds Are More Suitable Carriers of Placental Mesenchymal Stromal Cells Than Collagen/Elastin Scaffolds and Prevent Wound Contraction in a Mouse Model of Wound Healing

“…However, rodent wounds close due to contraction of the musculus panniculus carnosus, which is virtually non-existent in humans. This physiological difference creates difficulties in replicating the wound closure processes of human skin (Wang et al, 2013;Hu et al, 2018b). To overcome this problem, a short-term (e.g., 8-day) experiment in which no obvious contraction occurs is preferable (Tuca et al, 2016;Ertl et al, 2018).…”

Single-Cell Gene Expression Analysis and Evaluation of the Therapeutic Function of Murine Adipose-Derived Stromal Cells (ASCs) from the Subcutaneous and Visceral Compartment

“…The paracrine secretion of numerous addition, an increase in both recruitment and functionality of progenitor cells from the blood to the wound, could be demonstrated by ASC therapy [6]. The model of the mouse wound for the evaluation of cell therapeutic effects has long been established [28], and the positive effect of ASCs on wound healing has already been demonstrated several times. The ASC therapy was able to positively influence wound healing in the murine model even in the context of diabetes mellitus type II and obesity [29].…”

Electrospun Biomaterials in the Treatment and Prevention of Scars in Skin Wound Healing

“…This physiological difference therefore creates difficulties to replicate the wound closure processes of human skin. This is a universal problem, one that is noted in much recent literature (Wang et al, 2013;Hu et al, 2018). Wang et al discussed this problem, proposing an alternative model which involved splinting rodent wounds to inhibit contraction and force re-epithelization.…”