{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:47:40Z","timestamp":1777510060049,"version":"3.51.4"},"reference-count":68,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23H03034"],"award-info":[{"award-number":["23H03034"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    Mesenchymal stromal cells (MSCs) have been shown to exert therapeutic effects by modulating various cell types, including vascular endothelial cells, immune cells, and resident stem cells, at sites of tissue injury. Recent studies have highlighted the importance of MSC\u2013macrophage interactions in suppressing inflammation and promoting tissue regeneration; however, the underlying mechanisms remain poorly understood. In this study, we administered MSCs intratracheally to mice with bleomycin (BLM)-induced lung injury and investigated their effects on alveolar macrophages (AvMs), defined as CD64\n                    <jats:sup>High<\/jats:sup>\n                    \/F4\/80\n                    <jats:sup>High<\/jats:sup>\n                    \/Siglecf\n                    <jats:sup>High<\/jats:sup>\n                    \/CD11b\n                    <jats:sup>Negative<\/jats:sup>\n                    . MSC transplantation alleviated loss of AvMs observed after BLM treatment. Transcriptomic profiling of AvMs revealed increased expression of genes associated with cell survival, oxidative stress resistance, and efferocytosis. Among them, Sesn2 was notably upregulated.\n                    <jats:italic toggle=\"yes\">Ex vivo<\/jats:italic>\n                    experiments using isolated AvMs demonstrated that lactate treatment upregulated both\n                    <jats:italic toggle=\"yes\">Hypoxia inducible factor 1 alpha<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Hif1a<\/jats:italic>\n                    ) and\n                    <jats:italic toggle=\"yes\">Sestrin 2<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Sesn2<\/jats:italic>\n                    ), and that siRNA-mediated suppression of\n                    <jats:italic toggle=\"yes\">Hif1a<\/jats:italic>\n                    attenuated the lactic acid\u2013induced increase in\n                    <jats:italic toggle=\"yes\">Sesn2<\/jats:italic>\n                    expression. These findings provide mechanistic insight into how MSCs exert tissue-protective functions via the modulation of tissue-resident macrophages, and identify\n                    <jats:italic toggle=\"yes\">Sesn2<\/jats:italic>\n                    as a key molecule involved in this process. Our study underscores the immunomodulatory capacity of MSCs and their therapeutic relevance in lung injury.\n                  <\/jats:p>","DOI":"10.1177\/09636897251397044","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:20:49Z","timestamp":1765527649000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal stromal cells preserve alveolar macrophages by inducing Sesn2 expression via lactic acid production in a mouse model of bleomycin-induced lung injury"],"prefix":"10.1177","volume":"34","author":[{"given":"Tatsufumi","family":"Mori","sequence":"first","affiliation":[{"name":"Kindai University Life Science Research Institute, Kindai University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsumi","family":"Iwawaki","sequence":"additional","affiliation":[{"name":"Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Hospital, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanae","family":"Shigi","sequence":"additional","affiliation":[{"name":"Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Hospital, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Takehara","sequence":"additional","affiliation":[{"name":"Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Hospital, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Takenaka","sequence":"additional","affiliation":[{"name":"Toray Precision Co., Ltd., Shiga, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kindai University Faculty of Medicine, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5310-4749","authenticated-orcid":false,"given":"Takeshi","family":"Teramura","sequence":"additional","affiliation":[{"name":"Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Hospital, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.09.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.05.004"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01022-z"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103427"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-024-05150-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1155\/sci\/6324980"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph16091334"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26834-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.02.003"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2009.09.004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-024-00347-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaz0749"},{"key":"e_1_3_3_14_2","article-title":"Human Wharton\u2019s jelly mesenchymal stem cells and their extracellular vesicles in the management of bleomycin-induced lung injury in model animals: a comparative preclinical study focused on histomorphometric analysis","author":"Krishnan A","unstructured":"Krishnan A, Harikrishnan VS, Sabareeswaran A, Kasoju N. Human Wharton\u2019s jelly mesenchymal stem cells and their extracellular vesicles in the management of bleomycin-induced lung injury in model animals: a comparative preclinical study focused on histomorphometric analysis. Curr Stem Cell Res Ther. Epub 2025 Apr 25.","journal-title":"Curr Stem Cell Res Ther"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-023-00266-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szad034"},{"key":"e_1_3_3_17_2","article-title":"Are mesenchymal stem cells able to manage cytokine storm in COVID-19 patients? A review of recent studies","volume":"18","author":"Kaffash Farkhad N","year":"2021","unstructured":"Kaffash Farkhad N, Reihani H, Sedaghat A, Moghadam AA, Moghadam AB, Tavakol-Afshari J. Are mesenchymal stem cells able to manage cytokine storm in COVID-19 patients? A review of recent studies. Regen Ther. 2021;18:152\u201360.","journal-title":"Regen Ther"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0198-7"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1367"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0379"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368911X565038a"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368909788809857"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3600"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.03.008"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35604-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.173832"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0082-y"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szac032"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02960-7"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-015-0288-1"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12939"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1177\/09636897211024942"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1177\/0963689718787501"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/09636897231184611"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.62347\/JAWM2040"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70291-7"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00148.2020"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02335-4"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-14846-y"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0701-x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170501"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20162152"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.111975"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.6480"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00128-20"},{"issue":"19","key":"e_1_3_3_46_2","article-title":"Inhibition of alveolar macrophage pyroptosis reduces lipopolysaccharide-induced acute lung injury in mice","volume":"128","author":"Wu DD","year":"2015","unstructured":"Wu DD, Pan PH, Liu B, Su XL, Zhang LM, Tan HY, Cao Z, Zhou ZR, Li HT, Li HS, Huang L, et al. Inhibition of alveolar macrophage pyroptosis reduces lipopolysaccharide-induced acute lung injury in mice. Chin Med J (Engl). 2015;128(19):2638\u201345.","journal-title":"Chin Med J (Engl)"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2022.12.006"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0756-5"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1095569"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.08.018"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5233"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.10.017"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03970-z"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05669-4"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.11.002"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118941"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2024.07.004"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1183081"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03549-4"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2243"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8623"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113746"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105502"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1678-1"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202301722R"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1427739"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046571"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06409-6"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00250.2011"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897251397044","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09636897251397044","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897251397044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:36:20Z","timestamp":1777390580000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09636897251397044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":68,"alternative-id":["10.1177\/09636897251397044"],"URL":"https:\/\/doi.org\/10.1177\/09636897251397044","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"article-number":"09636897251397044"}}