PMID- 33906978 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220426 IS - 2005-3606 (Print) IS - 2005-5447 (Electronic) IS - 2005-3606 (Linking) VI - 14 IP - 3 DP - 2021 Aug 30 TI - Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Regulate Macrophage Polarization to Attenuate Systemic Lupus Erythematosus-Associated Diffuse Alveolar Hemorrhage in Mice. PG - 331-340 LID - 10.15283/ijsc20156 [doi] AB - BACKGROUND AND OBJECTIVES: To investigate the effect and the underlying mechanism of exosomes secreted by human umbilical cord mesenchymal stem cells (hUCMSCs) on diffuse alveolar hemorrhage (DAH) in murine lupus. METHODS AND RESULTS: Exosomes were extracted from cultured hUCMSCs by ultracentrifugation. The expressions of exosome markers (Alix, CD63 and TSG101) were measured for identification of hUCMSC-derived exosomes (hUCMSC-exosomes). The alveolar hemorrhage of DAH mice was revealed by H&E staining. The primary alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) of DAH mice. The expressions of M1 macrophage markers (iNOS, IL-6, TNF-alpha and IL-1beta) and M2 macrophage markers (Arg1, IL-10, TGF-beta and chi3l3) were detected. Flow cytometry measured the ratio of M1/M2 macrophages. ELISA measured the secretion of pro-inflammatory cytokines (IL-6 and TNF-alpha) and anti-inflammatory cytokines (IL-10 and TGF-beta). DAH mice had hemorrhage and small-vessel vasculitis in the lung, with neutrophil and monocyte infiltration observed around the capillary and small artery. Furthermore, increases of IL-6 and TNF-alpha, and decreases of IL-10 and TGF-beta were detected in the BALF of DAH mice. M1 makers were overexpressed in alveolar macrophages of DAH mice while M2 makers were lowly expressed. DAH mice had a higher proportion of M1 macrophages than M2 macrophages. After hUCMSC-exosome or methylprednisolone treatment in DAH mice, the alveolar injuries and inflammatory responses were attenuated, and the proportion of M2 macrophages was increased. CONCLUSIONS: hUCMSC-exosomes attenuate DAH-induced inflammatory responses and alveolar hemorrhage by regulating macrophage polarization. FAU - Chen, Xun AU - Chen X AD - Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. FAU - Wei, Qing AU - Wei Q AD - Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. FAU - Sun, Hongmei AU - Sun H AD - Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. FAU - Zhang, Xiaobo AU - Zhang X AD - Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. FAU - Yang, Changrong AU - Yang C AD - Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. FAU - Tao, Ying AU - Tao Y AD - Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. FAU - Nong, Guangmin AU - Nong G AD - Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. LA - eng PT - Journal Article PL - Korea (South) TA - Int J Stem Cells JT - International journal of stem cells JID - 101497587 PMC - PMC8429939 OTO - NOTNLM OT - Diffuse alveolar hemorrhage OT - Exosome OT - Human umbilical cord mesenchymal stem cells OT - M1 macrophage OT - M2 macrophage OT - Systemic lupus erythematosus COIS- Potential Conflict of Interest The authors have no conflicting financial interest. EDAT- 2021/04/29 06:00 MHDA- 2021/04/29 06:01 PMCR- 2021/04/30 CRDT- 2021/04/28 05:46 PHST- 2020/09/28 00:00 [received] PHST- 2020/12/24 00:00 [revised] PHST- 2021/01/28 00:00 [accepted] PHST- 2021/04/29 06:00 [pubmed] PHST- 2021/04/29 06:01 [medline] PHST- 2021/04/28 05:46 [entrez] PHST- 2021/04/30 00:00 [pmc-release] AID - ijsc20156 [pii] AID - ijsc-14-3-331 [pii] AID - 10.15283/ijsc20156 [doi] PST - ppublish SO - Int J Stem Cells. 2021 Aug 30;14(3):331-340. doi: 10.15283/ijsc20156.