Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Monocyte Transplantation Enhances Cutaneous Wound Repair
Graham G. Walmsley, B.A., Michael S. Hu, MD, Kipp Weiskopf, BA, Zeshaan N. Maan, MD, Dominic Duscher, MD, Robert Rennert, MD, Michael Januszyk, MD, Ruth Tevlin, MD, David Atashroo, MD, Kshemendra Seanarath-Yapa, MD, Alexander Whittam, BA, Elizabeth Zielins, MD, Owen Marecic, BA, Hermann P. Lorenz, MD, Irving L. Weissman, MD, Geoffrey C. Gurtner, MD, Michael T. Longaker, MD.
Stanford University, Stanford, CA, USA.

PURPOSE:
Monocytes are one of the first cell types to arrive at the site of cutaneous wounding and are critical to the initiation and subsequent orchestration of the later stages of wound healing, including angiogenesis, reepithelialization, and remodeling. We have previously shown that transplantation of macrophages into splinted excisional wounds on wild type (FVB/NJ) and diabetic mice (FVB.BKS(D)-Leprdb/ChuaJ) significantly increases the rate of wound healing. Here, we expand the analysis to focus on the transplantation of monocytes derived from human donors.
METHODS:
Human monocytes were isolated from peripheral blood, seeded on pullulan-collagen hydrogels, and transplanted into splinted excisional wounds on the backs of immunodeficient nude (Foxn1nu) mice on day 0 of wounding. Wounds were analyzed for progression of wound healing and time to complete healing. Histologic analysis revealed the localization and differentiation status of transplanted monocytes through the time course of wound healing.
RESULTS:
Human monocyte-seeded hydrogels significantly improved healing compared to un-seeded control hydrogels with an average time to complete healing of 17.8 days in the monocyte group versus 21 days in the control group (*p<0.005). Histologic analysis revealed that transplanted human monocytes differentiated primarily into M2 wound phenotype macrophages by day 2 following transplantation. Endogenous mouse macrophages within the wound site displayed a similar phenotype. Transplanted monocytes persisted in the wound site until day 8 of wound healing. Although the rate of wound healing was increased, endpoint scar size and quality was not affected in wounds receiving human monocytes as compared to control-treated wounds.
CONCLUSION:
Here we demonstrate that by transplanting human monocytes into splinted excisional wounds the rate of wound healing can be significantly accelerated with no adverse impact on the quality of repair in nude mice. Given that monocytes can be readily isolated by peripheral blood draw without in vitro manipulation prior to transplantation, these findings hold promise for translational medicine aimed at accelerating wound healing.


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