Granulocyte colony stimulating factor promotes scarless tissue regeneration

• Main Authors: HUANG, Jianhe, SATI, Satish: MURPHY, SPENCER, Casey A., RAPP, Emmanuel, PROUTY, Stephen M., KORTE, Scott, AHART, Olivia, SHENG, Emily, KERSH, Anna E., LEUNG, Denis, LEUNG, Thomas H., LEUNG, Denis H. Y.
• Format: text
• Language: English
• Published: Institutional Knowledge at Singapore Management University 2024
• Subjects: Cell and Developmental Biology; Econometrics
• Online Access: https://ink.library.smu.edu.sg/soe_research/2772; https://ink.library.smu.edu.sg/context/soe_research/article/3771/viewcontent/PIIS2211124724010933_pvoa_nc_nd.pdf
• Institution: Singapore Management University

Mammals typically heal with fibrotic scars, and treatments to regenerate human skin and hair without a scar remain elusive. We discovered that mice lacking C-X-C motif chemokine receptor 2 (CXCR2 knockout [KO]) displayed robust and complete tissue regeneration across three different injury models: skin, hair follicle, and cartilage. Remarkably, wild-type mice receiving plasma from CXCR2 KO mice through parabiosis or injections healed wounds scarlessly. A comparison of circulating proteins using multiplex ELISA revealed a 24-fold higher plasma level of granulocyte colony stimulating factor (G-CSF) in CXCR2 KO blood. Local injections of G-CSF into wild-type (WT) mouse wound beds reduced scar formation and increased scarless tissue regeneration. G-CSF directly polarized macrophages into an anti-inflammatory phenotype, and both CXCR2 KO and G-CSF-treated mice recruited more anti-inflammatory macrophages into injured areas. Modulating macrophage activation states at early time points after injury promotes scarless tissue regeneration and may offer a therapeutic approach to improve healing of human skin wounds.