Adipose-Derived Stem Cells Protect Skin Flaps against Ischemia/Reperfusion Injury via IL-6 Expression
Journal
Journal of Investigative Dermatology
Journal Volume
137
Journal Issue
6
Pages
1353-1362
Date Issued
2017
Author(s)
Pu C.-M.
Liu C.-W.
Liang C.-J.
Yen Y.-H.
Chen S.-H.
Jiang-Shieh Y.-F.
Chen Y.-C.
Abstract
Flap necrosis is the most frequent postoperative complication encountered in reconstructive surgery. We elucidated whether adipose-derived stem cells (ADSCs) and their derivatives might induce neovascularization and protect skin flaps during ischemia/reperfusion (I/R) injury. Flaps were subjected to 3 hours of ischemia by ligating long thoracic vessels and then to blood reperfusion. Qtracker-labeled ADSCs, ADSCs in conditioned medium (ADSC-CM), or ADSC exosomes (ADSC-Exo) were injected into the flaps. These treatments led to significantly increased flap survival and capillary density compared with I/R on postoperative day 5. IL-6 levels in the cell lysates or in conditioned medium were significantly higher in ADSCs than in Hs68 fibroblasts. ADSC-CM and ADSC-Exo increased tube formation. This result was corroborated by a strong decrease in skin repair after adding IL-6–neutralizing antibodies or small interfering RNA for IL-6 ADSCs. ADSC transplantation also increased flap recovery in I/R injury of IL-6–knockout mice. IL-6 was secreted from ADSCs through signal transducer and activator of transcription phosphorylation, and then IL-6 stimulated angiogenesis and enhanced recovery after I/R injury by the classic signaling pathway. The mechanism of skin recovery includes the direct differentiation of ADSCs into endothelial cells and the indirect effect of IL-6 released from ADSCs. ADSC-CM and ADSC-Exo could be used as off-the-shelf products for this therapy. ? 2017 The Authors
SDGs
Other Subjects
interleukin 6; mitogen activated protein kinase; small interfering RNA; STAT3 protein; interleukin 6; STAT3 protein; STAT3 protein, human; adipose derived stem cell; adult; angiogenesis; animal experiment; Article; capillary density; cell differentiation; cell lysate; conditioned medium; controlled study; cytokine release; endothelium cell; human; male; mouse; neovascularization (pathology); nonhuman; postoperative period; priority journal; protein expression; protein phosphorylation; reperfusion injury; skin fibroblast; skin flap; skin flap survival; stem cell transplantation; upregulation; adipose tissue; angiogenesis; animal; C57BL mouse; cell culture; cytology; disease model; fibroblast; genetics; graft survival; immunohistochemistry; immunology; metabolism; pathology; phosphorylation; procedures; randomization; reperfusion injury; stem cell; stem cell transplantation; surgical flaps; Adipose Tissue; Animals; Cells, Cultured; Disease Models, Animal; Fibroblasts; Graft Survival; Immunohistochemistry; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Phosphorylation; Random Allocation; Reperfusion Injury; STAT3 Transcription Factor; Stem Cell Transplantation; Stem Cells; Surgical Flaps
Publisher
Elsevier B.V.
Type
journal article