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It has been previously reported that mesenchymal stem cell (MSC) and endothelial progenitor cells (EPC) therapy have beneficial effects in experimental models of sepsis. The effects of coculture of MSC and EPC have not yet been used to treat sepsis. Therefore, the aim of this study was to investigate the therapeutic potential of EPC\u2009+\u2009MSC coculture on the residual effects of sepsis in a lipopolysaccharide (LPS)\u2010induced mice model. Coinjections of EPC\u2009+\u2009MSC significantly enhanced the survival rate of LPS\u2010induced mice, decreased concentrations of pro\u2010inflammatory cytokines, and increased the level of anti\u2010inflammatory cytokine. The LPS\u2010induced mice that were treated with EPC\u2009+\u2009MSC showed a notable reduction in pulmonary edema, hepatic enzymes, and C\u2010reactive protein level compared with the control group. Our results showed that coinjection of EPC\u2009+\u2009MSC up and downregulates Tie2 and TLR4\/MyD88 signaling pathways in LPS\u2010induced mice, respectively. Also, in vitro study showed that viability, adhesion, and migration in coculture cells is significantly decreased after being induced with 10\u2009\u03bcg\/ml LPS. Our results showed that LPS impaired the functional activity of the cocultured EPC\u2009+\u2009MSC via upregulation of the TLR4\/MyD88 signaling pathway, which may be associated with decreased pTie2\/Tie2 expression. In conclusion, coinjection of EPC and MSC modulated the TLR4\/MyD88 signaling pathway that leads to reduce the inflammatory response. This study may provide promising results for the introduction of cocultured cells to manage infectious diseases and balance the immune response through immune regulatory function.<\/jats:p>","DOI":"10.1002\/jcb.30133","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T11:34:39Z","timestamp":1629113679000},"page":"1791-1804","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mesenchymal stem cell and endothelial progenitor cells coinjection improves LPS\u2010induced lung injury via Tie2 activation and downregulation of the TLR4\/MyD88 pathway"],"prefix":"10.1002","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3174-4649","authenticated-orcid":false,"given":"Sadaf","family":"Hoseinnia","sequence":"first","affiliation":[{"name":"Department of Microbiology, North Tehran Branch Islamic Azad University Tehran 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