Abstract
The most common postoperative complication after reconstructive surgery is flap necrosis. Adipose-derived stem cells (ADSCs) and their secretomes are reported to mediate skin repair. This study was designed to investigate whether conditioned media from ADSCs (ADSC-CM) protects ischemia/reperfusion- (I/R-) induced injury in skin flaps by promoting cell proliferation and increasing the number of hair follicles. The mouse flap model of ischemia was ligating the long thoracic vessels for 3 h, followed by blood reperfusion. ADSC-CM was administered to the flaps, and their survival was observed on postoperative day 5. ADSC-CM treatment led to a significant increase in cell proliferation and the number of hair follicles. IL-6 levels in the lysate and CM from ADSCs were significantly higher than those from Hs68 fibroblasts. Furthermore, a strong decrease in cell proliferation and the number of hair follicles was observed after treatment with IL-6-neutralizing antibodies or si-IL-6-ADSC. In addition, ADSC transplantation increased flap repair, cell proliferation, and hair follicle number in I/R injury of IL-6-knockout mice. In conclusion, IL-6 secreted from ADSCs promotes the survival of I/R-induced flaps by increasing cell proliferation and the number of hair follicles. ADSCs represent a promising therapy for preventing skin flap necrosis following reconstructive and plastic surgery.
Highlights
Skin flap transplantation is frequently used in plastic and reconstructive surgery for its flexibility and convenience in repairing local tissue loss and its ability to correct tissue defects [1]
We demonstrated that IL-6 in Adipose-derived stem cells (ADSCs)-CM increased cell proliferation and the number of hair follicles in the skin flap model for I/R injury via manipulation of the long thoracic artery
The necrosis of the skin flap was clearly observed in the I/R mice, whereas the ADSC-CM treatment attenuated the I/R-induced necrotic area (Figure 1(a))
Summary
Skin flap transplantation is frequently used in plastic and reconstructive surgery for its flexibility and convenience in repairing local tissue loss and its ability to correct tissue defects [1]. The trouble with skin flap transplantation for plastic surgeons is necrosis, which is the major complication following flap surgery. Total or partial flap failure may require additional reconstruction. Such complications increase the risk of injury site infections and postoperative hospitalizations, and they increase medical expenses [2, 3]. Stem cellbased therapies for I/R injury are a new field of medicine for regenerating tissues [5]. ADSC transplantation was shown to induce angiogenesis in patients with critical limb ischemia and rats
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