American journal of translational research · 2026
GM-CSF and IL-1α secreted by cryopreserved porcine skin promote angiogenesis in burn wounds by activating the JAK2/STAT3 pathway.
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Liu Yuxing, Zuo Haibin, Shao Yang, Gao Cong, Liu Xinzhuang, Song Guodong
Аннотация
OBJECTIVE: Cryopreserved porcine skin (CPS) is widely applied in skin grafting for burns. In this study, we aimed to investigate the effects and underlying mechanisms of CPS on burn wound healing.
METHODS: Cryopreserved porcine skins were acquired. Guinea pig burn models were established and grafted with thawed-CPS. Human umbilical vein endothelial cells (HUVECs) were cultured in CPS-conditioned medium. Histological structure was assessed by hematoxylin-eosin (HE) staining. Protein levels were detected using enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemistry. HUVECs proliferation was evaluated by 5-ethynyl-2'-deoxyuridine (EdU) assay. The invasion and migration of HUVECs were analyzed via Transwell assay. Tube formation was also assessed.
RESULTS: CPS maintained its structural integrity and cellular viability, with lower antigenicity compared with fresh porcine skin. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-1 alpha (IL-1α) secreted by CPS were detected in the CPS-grafted burned tissue. Moreover, CPS grafting accelerated wound healing and angiogenesis in burned guinea pigs. In vitro, CPS-conditioned medium enhanced the proliferation, invasion, migration, and tube formation of HUVECs, as well as activated the JAK2/STAT3 pathway. Neutralizing antibodies against GM-CSF and IL-1α synergistically reversed the pro-angiogenic effects of CPS in vivo and in vitro. Additionally, JAK2 inhibitor AG490 abolished the enhanced proliferation, invasion, migration, and tube formation of HUVECs induced by CPS-conditioned medium.
CONCLUSION: We confirmed that CPS-secreted GM-CSF and IL-1α promoted angiogenesis in burn tissue by activating the JAK2/STAT3 pathway, thereby revealing an active therapeutic role of CPS for burn wound healing and offering theoretical support for its clinical application.
METHODS: Cryopreserved porcine skins were acquired. Guinea pig burn models were established and grafted with thawed-CPS. Human umbilical vein endothelial cells (HUVECs) were cultured in CPS-conditioned medium. Histological structure was assessed by hematoxylin-eosin (HE) staining. Protein levels were detected using enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemistry. HUVECs proliferation was evaluated by 5-ethynyl-2'-deoxyuridine (EdU) assay. The invasion and migration of HUVECs were analyzed via Transwell assay. Tube formation was also assessed.
RESULTS: CPS maintained its structural integrity and cellular viability, with lower antigenicity compared with fresh porcine skin. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-1 alpha (IL-1α) secreted by CPS were detected in the CPS-grafted burned tissue. Moreover, CPS grafting accelerated wound healing and angiogenesis in burned guinea pigs. In vitro, CPS-conditioned medium enhanced the proliferation, invasion, migration, and tube formation of HUVECs, as well as activated the JAK2/STAT3 pathway. Neutralizing antibodies against GM-CSF and IL-1α synergistically reversed the pro-angiogenic effects of CPS in vivo and in vitro. Additionally, JAK2 inhibitor AG490 abolished the enhanced proliferation, invasion, migration, and tube formation of HUVECs induced by CPS-conditioned medium.
CONCLUSION: We confirmed that CPS-secreted GM-CSF and IL-1α promoted angiogenesis in burn tissue by activating the JAK2/STAT3 pathway, thereby revealing an active therapeutic role of CPS for burn wound healing and offering theoretical support for its clinical application.