TY - JOUR
T1 - An Improved Humanized Mouse Model for Excisional Wound Healing Using Double Transgenic Mice
AU - Hu, Michael S.
AU - Cheng, Justin
AU - Borrelli, Mimi R.
AU - Leavitt, Tripp
AU - Walmsley, Graham G.
AU - Zielins, Elizabeth R.
AU - Hong, Wan Xing
AU - Cheung, Alexander T.M.
AU - Duscher, Dominik
AU - Maan, Zeshaan N.
AU - Irizarry, Dre M.
AU - Stephan, Brad
AU - Parsa, Fereydoun Don
AU - Wan, Derrick C.
AU - Gurtner, Geoffrey C.
AU - Lorenz, Hermann Peter
AU - Longaker, Michael T.
N1 - Funding Information:
This work was supported, in part, by NIH grant K08 DE024269 (to D.C.W.), the Child Health Research Institute at Stanford University (to D.C.W.), NIH grant R01 GM087609 (to H.P.L.), a Gift from Ingrid Lai and Bill Shu in honor of Anthony Shu (to H.P.L.), the Hagey Laboratory for Pediatric Regenerative Medicine and Children’s Surgical Research Program (to D.C.W., H.P.L., and M.T.L.), the Gunn/Olivier Fund (to M.T.L.). Additional funding was provided by the American Society of Maxillofacial Surgeons (ASMS)/Maxillofacial Surgeons Foundation (MSF) Research Grant Award (to M.S.H., H.P.L., and M.T.L.), the California Institute for Regenerative Medicine (CIRM) Clinical Fellow training grant TG2-01159 (to M.S.H.), the Stanford University School of Medicine Transplant and Tissue Engineering Fellowship Award (to M.S.H.), and the Sarnoff Cardiovascular Research Foundation (to W.X.H.).
Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc. 2018.
PY - 2018/1
Y1 - 2018/1
N2 - 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 ROSAmT/mG reporter mice. Full-thickness excisional wounds were created in K14-Cre/ROSAmT/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/ROSAmT/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/ROSAmT/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/ROSAmT/mG double transgenic mice and fluorescence imaging.
AB - 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 ROSAmT/mG reporter mice. Full-thickness excisional wounds were created in K14-Cre/ROSAmT/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/ROSAmT/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/ROSAmT/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/ROSAmT/mG double transgenic mice and fluorescence imaging.
KW - mouse model
KW - transgenic mice
KW - wound healing
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U2 - 10.1089/wound.2017.0772
DO - 10.1089/wound.2017.0772
M3 - Article
AN - SCOPUS:85040460205
SN - 2162-1918
VL - 7
SP - 11
EP - 17
JO - Advances in Wound Care
JF - Advances in Wound Care
IS - 1
ER -