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At present, there is no effective and specific therapy for ALI\/ARDS. Mesenchymal stem cells (MSCs) have well\u2010known therapeutic potential in patients with ALI\/ARDS. Heme oxygenase\u20101 (HO\u20101), a cytoprotective enzyme, possesses antioxidative, anti\u2010inflammatory, and antiapoptotic effects. Thus, a combination of MSC transplantation with HO\u20101 delivery may have an additional protective effect against ALI\/ARDS. This study investigated the effect of HO\u20101\u2010modified bone\u2010marrow\u2013derived MSCs (MSCs\u2010HO\u20101) on lipopolysaccharide (LPS)\u2010induced ALI and its underlying mechanisms. We established MSCs\u2010HO\u20101 through lentiviral transduction. The ALI rat model was established by successive LPS inhalations following injection with MSCs\u2010HO\u20101. The survival rate, histological changes in the lungs, total protein concentration and neutrophil counts in bronchoalveolar lavage fluid, lung wet\/dry weight ratio, cytokine levels in serum and lungs, nuclear transcription factor\u2010\u03baB activity, and protein expression of Toll\u2010like receptor 4 signaling adaptors were examined. Furthermore, the cell viability, apoptosis, and paracrine activity of MSCs\u2010HO\u20101 were examined under inflammatory stimuli in vitro. MSCs\u2010HO\u20101 injection improved these parameters compared with primary unmodified MSCs. Moreover, MSCs\u2010HO\u20101 had superior prosurvival and antiapoptotic properties and enhanced paracrine functions in vitro. Therefore, MSCs\u2010HO\u20101 exert an enhanced protective effect to alleviate LPS\u2010induced ALI in rats, and the mechanisms may be partially associated with superior prosurvival, antiapoptosis, and enhanced paracrine functions of MSCs\u2010HO\u20101. These findings provide a novel insight into MSC\u2010based therapeutic strategies for treating ALI\/ARDS.<\/jats:p>","DOI":"10.1002\/jcp.27488","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T11:21:20Z","timestamp":1540552880000},"page":"7301-7319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Mesenchymal stem cells overexpressing heme oxygenase\u20101 ameliorate lipopolysaccharide\u2010induced acute lung injury in rats"],"prefix":"10.1002","volume":"234","author":[{"given":"Xuxin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Navy General Hospital of the PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Navy General Hospital of the PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of Changsha Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Navy General Hospital of the PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Navy General Hospital of the PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huasong","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Navy General Hospital of the PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiguang","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Navy General Hospital of the PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2167-2258","authenticated-orcid":false,"given":"Zhihai","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Navy General Hospital of the PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,26]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2006.137"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.15.5492-5505.2002"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-075481"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0222-1"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2016.64"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-017-0639-9"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000492847"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181f226f3"},{"key":"e_1_2_7_1_10_1","first-page":"1921","article-title":"Paralemmin\u20103 contributes to lipopolysaccharide\u2010induced inflammatory response and is involved in lipopolysaccharide\u2010Toll\u2010like receptor\u20104 signaling in alveolar macrophages","volume":"40","author":"Chen X. 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