Article
Topical application of apoptotic peripheral mononuclear blood cell secretome enhances epithelisation in genetically diabetic db/db mice
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Published: | August 16, 2017 |
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Introduction: A major complication in diabetic patients is foot ulcer. However, to date no sufficient therapy can be offered to those patients. The supernatant of apoptotic peripheral mononuclear blood cells (APOSEC), has previously shown beneficial effects in tissue regeneration and wound healing in a variety of organs, but has not been tested in a murine model of diabetic wound healing.
Materials and methods: We used a full-thickness wound healing model in genetically diabetic db/db mice. APOSEC (25 Mio/ml, 12.5 Mio/ml, 2.5 Mio/ml) or control were applied in each 12 mice to the wound site for ten days. Wound size was assessed until day 25 by tracing the wound on acrylic foil and using a stereoscopic camera for 3D wound measurement (circumference, surface area). The histological stainings Masson’s trichrome, Weigert’s elastic stain, H&E and immunohistochemical stainings (CD31, CD45, K10, ki67) were performed.
Results: Wound circumference (52.1% vs. 38.3%, p<0.05), wound surface area (79.3% vs. 64.7%, p<0.05) and wound size assessed planimetrically (67.2% vs. 56.7%, p<0.05) showed a significantly improvedfold decrease in mice treated with APOSEC 25 Mio/ml compared to control at day 18. However, histopathological analyses revealed no differences between APOSEC and control in angiogenesis (p=0.44), inflammation (p=0.68), collagen (p=0.89) or elastic fibre deposition and proliferation (p=0.84) in the wound zone. Continuous K10 staining was observed only in APOSEC 25 Mio/ml and 12.5 Mio/ml treated mice and K10 staining was enhanced in the APOSEC groups compared to control (p<0.0001).
Conclusion: We showed that local administration of APOSEC to a full-thickness wound significantly enhances its healing in genetically diabetic mice. Although chronic diabetic ulcer displays a severe burden, hitherto no adequate therapy to address this problem has been introduced. The secretome of apoptotic PBMCs may offer a promising potential for skin regeneration in diabetic wound healing.
Figure 1 [Fig. 1]