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MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid-macrophage model.
Zhu, Jiaqi; Zhou, Jiahang; Feng, Bing; Pan, Qiaoling; Yang, Jinfeng; Lang, Guanjing; Shang, Dandan; Zhou, Jianya; Li, Lanjuan; Yu, Jiong; Cao, Hongcui.
Afiliação
  • Zhu J; State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Zhou J; Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
  • Feng B; State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Pan Q; State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Yang J; State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Lang G; State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Shang D; State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Zhou J; Jinan Microecological Biomedicine Shandong Laboratory, Jinan, 250117, Shandong, China.
  • Li L; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Yu J; Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, China.
  • Cao H; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd, Hangzhou, 310003, China.
Cell Mol Life Sci ; 81(1): 124, 2024 Mar 11.
Article em En | MEDLINE | ID: mdl-38466420
ABSTRACT
Acute lung injury (ALI) is an inflammatory disease associated with alveolar injury, subsequent macrophage activation, inflammatory cell infiltration, and cytokine production. Mesenchymal stem cells (MSCs) are beneficial for application in the treatment of inflammatory diseases due to their immunomodulatory effects. However, the mechanisms of regulatory effects by MSCs on macrophages in ALI need more in-depth study. Lung tissues were collected from mice for mouse lung organoid construction. Alveolar macrophages (AMs) derived from bronchoalveolar lavage and interstitial macrophages (IMs) derived from lung tissue were co-cultured, with novel matrigel-spreading lung organoids to construct an in vitro model of lung organoids-immune cells. Mouse compact bone-derived MSCs were co-cultured with organoids-macrophages to confirm their therapeutic effect on acute lung injury. Changes in transcriptome expression profile were analyzed by RNA sequencing. Well-established lung organoids expressed various lung cell type-specific markers. Lung organoids grown on spreading matrigel had the property of functional cells growing outside the lumen. Lipopolysaccharide (LPS)-induced injury promoted macrophage chemotaxis toward lung organoids and enhanced the expression of inflammation-associated genes in inflammation-injured lung organoids-macrophages compared with controls. Treatment with MSCs inhibited the injury progress and reduced the levels of inflammatory components. Furthermore, through the nuclear factor-κB pathway, MSC treatment inhibited inflammatory and phenotypic transformation of AMs and modulated the antigen-presenting function of IMs, thereby affecting the inflammatory phenotype of lung organoids. Lung organoids grown by spreading matrigel facilitate the reception of external stimuli and the construction of in vitro models containing immune cells, which is a potential novel model for disease research. MSCs exert protective effects against lung injury by regulating different functions of AMs and IMs in the lung, indicating a potential mechanism for therapeutic intervention.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia / Lesão Pulmonar Aguda / Células-Tronco Mesenquimais Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia / Lesão Pulmonar Aguda / Células-Tronco Mesenquimais Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article