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Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing
Ruoyu Mu1; Zhe Zhang1,2; Congwei Han1,3; Yiming Niu1,3; Zhen Xing3; Zhencheng Liao1; Jinzhi Xu3; Ningyi Shao4; Guokai Chen4; Junfeng Zhang3; Lei Dong3; Chunming Wang1,2,5
2023-02-08
Source PublicationEMBO Molecular Medicine
ISSN1757-4676
Volume15Issue:2Pages:e16671
Abstract

Nonhealing diabetic wounds, with persistent inflammation and damaged vasculature, have failed conventional treatments and require comprehensive interference. Here, inspired by tumor-associated macrophages (TAMs) that produce abundant immunosuppressive and proliferative factors in tumor development, we generate macrophages to recapitulate TAMs' reparative functions, by culturing normal macrophages with TAMs' conditional medium (TAMs-CM). These TAMs-educated macrophages (TAMEMs) outperform major macrophage phenotypes (M0, M1, or M2) in suppressing inflammation, stimulating angiogenesis, and activating fibroblasts in vitro. When delivered to skin wounds in diabetic mice, TAMEMs efficiently promote healing. Based on TAMs-CM's composition, we further reconstitute a nine-factor cocktail to train human primary monocytes into TAMEMs, which fully resemble TAMEMs' functions without using tumor components, thereby having increased safety and enabling the preparation of autologous cells. Our study demonstrates that recapitulating TAMs' unique reparative activities in nontumor cells can lead to an effective cell therapeutic approach with high translational potential for regenerative medicine.

KeywordAdoptive Cell Transfer Diabetes Macrophages Tumor-associated Macrophages (Tams) Wound Healing
DOI10.15252/emmm.202216671
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaResearch & Experimental Medicine
WOS SubjectMedicine, Research & Experimental
WOS IDWOS:000930996500004
Scopus ID2-s2.0-85144261397
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Citation statistics
Document TypeJournal article
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Faculty of Health Sciences
Institute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
DEPARTMENT OF PHARMACEUTICAL SCIENCES
Corresponding AuthorLei Dong; Chunming Wang
Affiliation1.Institute of Chinese Medical Sciences & State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR, China
2.Zhuhai UM Science & Technology Research Institute, University of Macau, Hengqin, China
3.School of Life Sciences & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
4.Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macau SAR, China
5.Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macau SAR, Chin
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences;  University of Macau;  Faculty of Health Sciences
Recommended Citation
GB/T 7714
Ruoyu Mu,Zhe Zhang,Congwei Han,et al. Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing[J]. EMBO Molecular Medicine, 2023, 15(2), e16671.
APA Ruoyu Mu., Zhe Zhang., Congwei Han., Yiming Niu., Zhen Xing., Zhencheng Liao., Jinzhi Xu., Ningyi Shao., Guokai Chen., Junfeng Zhang., Lei Dong., & Chunming Wang (2023). Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing. EMBO Molecular Medicine, 15(2), e16671.
MLA Ruoyu Mu,et al."Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing".EMBO Molecular Medicine 15.2(2023):e16671.
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