{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:32:47Z","timestamp":1787837567666,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["21\u201004607X"],"award-info":[{"award-number":["21\u201004607X"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007543","name":"Grantov\u00e1 Agentura, Univerzita Karlova","doi-asserted-by":"publisher","award":["98723"],"award-info":[{"award-number":["98723"]}],"id":[{"id":"10.13039\/100007543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mitochondrial transfer is becoming recognized as an important immunomodulatory mechanism used by mesenchymal stem cells (MSCs) to influence immune cells. While effects on T cells and macrophages have been documented, the influence on B cells remains unexplored. This study investigates the modulation of B lymphocyte fate by MSC\u2010mediated mitochondrial transfer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MSCs labelled with MitoTracker dyes or derived from mito::mKate2 transgenic mice were co\u2010cultured with splenocytes. Flow cytometry assessed mitochondrial transfer, reactive oxygen species (ROS) levels, apoptosis and mitophagy. Glucose uptake was measured using the 2\u2010NBDG assay. RNA sequencing analysed gene expression changes in CD19+ mitochondria recipients and nonrecipients. Pathway analysis identified affected processes. In an LPS\u2010induced inflammation model, mito::mKate2 MSCs were administered, and B cells from different organs were analysed for mitochondrial uptake and phenotypic changes. MSC\u2010derived mitochondria were also isolated to confirm uptake by FACS\u2010sorted CD19+ cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MSCs transferred mitochondria to CD19+ cells, though less than to other immune cells. Transfer correlated with ROS levels and mitophagy induction. Mitochondria were preferentially acquired by activated B cells, as indicated by increased CD69 expression and glycolytic activity. Bidirectional transfer occurred, with immune cells exchanging dysfunctional mitochondria for functional ones. CD19+ recipients exhibited increased viability, proliferation and altered gene expression, with upregulated cell division genes and downregulated antigen presentation genes. In\u00a0vivo, mitochondrial acquisition reduced B cell activation and inflammatory cytokine production. Pre\u2010sorted B cells also acquired isolated mitochondria, exhibiting a similar anti\u2010inflammatory phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight mitochondrial trafficking as a key MSC\u2010immune cell interaction mechanism with immunomodulatory therapeutic potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70073","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T08:08:00Z","timestamp":1747296480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mesenchymal stem cell\u2010mediated mitochondrial transfer regulates the fate of B lymphocytes"],"prefix":"10.1111","volume":"55","author":[{"given":"Veronika","family":"Somova","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Jaborova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianka","family":"Porubska","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Vasek","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Fikarova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Prevorovsky","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Nahacka","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Therapy Institute of Biotechnology, Czech Academy of Sciences  Prague\u2010West Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Neuzil","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Therapy Institute of Biotechnology, Czech Academy of Sciences  Prague\u2010West Czech Republic"},{"name":"Department of Physiology, Faculty of Science Charles University  Prague Czech Republic"},{"name":"School of Pharmacy and Medical Science Griffith University  Southport Queensland Australia"},{"name":"First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3622-376X","authenticated-orcid":false,"given":"Magdalena","family":"Krulova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Science Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1083\/JCB.202211044\/213873"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02194-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCONREL.2022.01.025"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13287-018-1012-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4110\/IN.2023.23.E45"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13578-022-00805-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS242115788"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00440-z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS22063245"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201701-0170OC"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/STEM.2372"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/STEM.3375"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28338-0"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-021-90115-8"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.15252\/EMBR.201948052"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13287-019-1307-9"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13287-022-03219-X"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","unstructured":"IrwinRM ThomasMA FaheyMJ May\u00e1nMD SmythJW DelcoML.Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes.bioRxiv. doi:10.1101\/2024.03.18.585552","DOI":"10.1101\/2024.03.18.585552"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4110\/IN.2018.18.E14"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.FREERADBIOMED.2019.06.004"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8838046"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/SCD.2011.0691"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00018-016-2233-Y"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PCBI.1006582"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.31083\/J.JIN2101038\/1757-448X-21-1-038.PDF"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JARE.2022.05.012"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1603547"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCONREL.2023.01.059"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CMET.2014.12.003"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.15252\/EMBJ.201695916"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YEXCR.2010.06.009"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/FEBS.15327"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M607122200"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(99)00010-1"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/JCS.104.3.917"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0291-z"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-019-40163-Y"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3892\/MMR.2015.4726"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/MOLECULES23030687"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2736"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.4266\/ACC.2018.00619"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.01746"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13054-020-03436-X"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/DVG.23087"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/TERM.2044"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12015-016-9703-3"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-023-44205-4"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/NMETH.3317"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/GIGASCIENCE\/GIAB008"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTP352"},{"key":"e_1_2_9_52_1","doi-asserted-by":"crossref","unstructured":"KleverovM ZenkovaD KamenevV SablinaM ArtyomovMN SergushichevAA.Phantasus: web\u2010application for visual and interactive gene expression analysis.bioRxiv. doi:10.1101\/2022.12.10.519861","DOI":"10.1101\/2022.12.10.519861"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.70073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T07:40:01Z","timestamp":1757922001000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.70073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":51,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/eci.70073"],"URL":"https:\/\/doi.org\/10.1111\/eci.70073","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]},"assertion":[{"value":"2025-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70073"}}