Abstract
BackgroundWhen the deer antler is cast, it leaves a cutaneous wound that can achieve scarless healing due to the presence of antler stem cells (ASCs). This provides an opportunity to study regenerative wound healing.MethodsIn this study, we investigated the therapeutic effects and mechanism of antler stem cell-conditioned medium (ASC-CM) on cutaneous wound healing in rats. In vitro, we investigated the effects of the ASC-CM on proliferation of HUVEC and NIH-3T3 cell lines. In vivo, we evaluated the effects of ASC-CM on cutaneous wound healing using full-thickness skin punch-cut wounds in rats.ResultsThe results showed that ASC-CM significantly stimulated proliferation of the HUVEC and NIH-3T3 cells in vitro. In vivo, completion of healing of the rat wounds treated with ASC-CM was on day 16 (± 3 days), 9 days (± 2 days) earlier than the control group (DMEM); the area of the wounds treated with ASC-CM was significantly smaller (p < 0.05) than the two control groups. Further molecular characterization showed that the ratios of Col3A1/Col1A2, TGF-β3/TGF-β1, MMP1/TIMP1, and MMP3/TIMP1 significantly increased (p < 0.01) in the healed tissue in the ASC-CM group.ConclusionsIn conclusion, ASC-CM effectively accelerated the wound closure rate and enhanced the quality of healing, which might be through transforming wound dermal fibroblasts into the fetal counterparts. Therefore, the ASC-CM may have potential to be developed as a novel cell-free therapeutic for scarless wound healing.
Highlights
When the deer antler is cast, it leaves a cutaneous wound that can achieve scarless healing due to the presence of antler stem cells (ASCs)
Determination of the optimal ratio of antler stem cell-conditioned medium (ASC-conditioned medium (CM)) in culture medium The first experiment was set out to determine the optimal ratio of the ASC-CM to DMEM in stimulating Human umbilical vein endothelial cells (HUVECs) proliferation
We found that compared to all four control media, ASC-CM (87.7% and 70.2% respectively) had the highest percentage of Ki-67-positive cells in both HUVEC (DMEM, 24.1%; Insulin like growth factor 1 (IGF1), 61.3%; facial periosteal cellconditioned medium (FP-CM), 48.2%; and mesenchymal stem cell-conditioned medium (MSCCM), 73.5%; p < 0.001, Fig. 3a, b) and NIH-3T3 (DMEM, 19.2%; IGF1, 42.6%; FP-CM, 37.8%; and mesenchymal stem cell (MSC)-CM, 62.4%; p < 0.001, Fig. 3a, c) cell lines
Summary
When the deer antler is cast, it leaves a cutaneous wound that can achieve scarless healing due to the presence of antler stem cells (ASCs). Mesenchymal stem cell (MSC) therapy has been reported as a novel approach in the wound healing field [3, 4]. It is known that MSCs promote wound healing through their differentiation potential, immunomodulatory properties, Deer antlers are the only known mammalian organ that can completely regenerate once cast from their. A previous study has shown that antler stem cells (ASCs) are unique in that they can initiate full regeneration of a mammalian organ, the deer antler, and promote perfect cutaneous wound healing in a very rapid manner prior to the antler regeneration [10]. From the point of view of safety and ethics, ASCs cannot be used directly in the clinical situation, and an alternative effective approach has to be taken to avoid these problems if the ASCs to be used in clinics
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