{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:13:45Z","timestamp":1775283225220,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM111899"],"award-info":[{"award-number":["R01GM111899"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Patients with hemorrhagic shock and trauma (HS\/T) are vulnerable to the endotheliopathy of trauma (EOT), characterized by vascular barrier dysfunction, inflammation, and coagulopathy. Cellular therapies such as mesenchymal stem cells (MSCs) and MSC extracellular vesicles (EVs) have been proposed as potential therapies targeting the EOT. In this study we investigated the effects of MSCs and MSC EVs on endothelial and epithelial barrier integrity in vitro and in vivo in a mouse model of HS\/T. This study addresses the\u00a0systemic effects of HS\/T on multiorgan EOT.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In vitro, pulmonary endothelial cell (PEC) and Caco-2 intestinal epithelial cell monolayers were treated with control media, MSC conditioned media (CM), or MSC EVs in varying doses and subjected to a thrombin or hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) challenge, respectively. Monolayer permeability was evaluated with a cell impedance assay, and intercellular junction integrity was evaluated with immunofluorescent staining. In vivo, a mouse model of HS\/T was used to evaluate the effects of lactated Ringer\u2019s (LR), MSCs, and MSC EVs on endothelial and epithelial intercellular junctions in the lung and small intestine as well as on plasma inflammatory biomarkers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>MSC EVs and MSC CM attenuated permeability and preserved intercellular junctions of the PEC monolayer in vitro<jats:italic>,<\/jats:italic> whereas only MSC CM was protective of the Caco-2 epithelial monolayer. In vivo, both MSC EVs and MSCs mitigated the loss of endothelial adherens junctions in the lung and small intestine, though only MSCs had a protective effect on epithelial tight junctions in the lung. Several plasma biomarkers including MMP8 and VEGF were elevated in LR- and EV-treated but not MSC-treated mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In conclusion, MSC EVs could be a potential cell-free therapy targeting endotheliopathy after HS\/T via preservation of the vascular endothelial barrier in multiple organs early after injury. Further research is needed to better understand the immunomodulatory effects of these products following HS\/T and to move toward translating these therapies into clinical studies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-024-05406-1","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T11:02:10Z","timestamp":1718967730000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Regulation of vascular endothelial integrity by mesenchymal stem cell extracellular vesicles after hemorrhagic shock and trauma"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2353-3312","authenticated-orcid":false,"given":"Mark","family":"Barry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alpa","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byron","family":"Miyazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay R.","family":"Vivona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Shimmin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Praneeti","family":"Pathipati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Callie","family":"Keane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Cuschieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibani","family":"Pati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"issue":"Suppl 1","key":"5406_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/SHK.0000000000000140","volume":"41","author":"DH Jenkins","year":"2014","unstructured":"Jenkins DH, Rappold JF, Badloe JF, et al. Trauma hemostasis and oxygenation research position paper on remote damage control resuscitation: definitions, current practice, and knowledge gaps. Shock. 2014;41(Suppl 1):3\u201312. https:\/\/doi.org\/10.1097\/SHK.0000000000000140.","journal-title":"Shock"},{"key":"5406_CR2","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1182\/asheducation-2013.1.656","volume":"2013","author":"JB Holcomb","year":"2013","unstructured":"Holcomb JB, Pati S. Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon\u2019s perspective. Hematology Am Soc Hematol Educ Program. 2013;2013:656\u20139. https:\/\/doi.org\/10.1182\/asheducation-2013.1.656.","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"5406_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2022.100107","volume":"14","author":"M Barry","year":"2022","unstructured":"Barry M, Pati S. Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation. Matrix Biol Plus. 2022;14: 100107. https:\/\/doi.org\/10.1016\/j.mbplus.2022.100107.","journal-title":"Matrix Biol Plus"},{"issue":"4","key":"5406_CR4","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1097\/SHK.0000000000000999","volume":"49","author":"DN Naumann","year":"2018","unstructured":"Naumann DN, Hazeldine J, Davies DJ, et al. Endotheliopathy of trauma is an on-scene phenomenon, and is associated with multiple organ dysfunction syndrome: a prospective observational study. Shock. 2018;49(4):420\u20138. https:\/\/doi.org\/10.1097\/SHK.0000000000000999.","journal-title":"Shock"},{"issue":"3","key":"5406_CR5","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1097\/SLA.0000000000001751","volume":"265","author":"PI Johansson","year":"2017","unstructured":"Johansson PI, Henriksen HH, Stensballe J, et al. Traumatic endotheliopathy: a prospective observational study of 424 severely injured patients. Ann Surg. 2017;265(3):597\u2013603. https:\/\/doi.org\/10.1097\/SLA.0000000000001751.","journal-title":"Ann Surg"},{"issue":"9","key":"5406_CR6","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1001\/jamasurg.2014.940","volume":"149","author":"NR Langan","year":"2014","unstructured":"Langan NR, Eckert M, Martin MJ. Changing patterns of in-hospital deaths following implementation of damage control resuscitation practices in US forward military treatment facilities. JAMA Surg. 2014;149(9):904\u201312. https:\/\/doi.org\/10.1001\/jamasurg.2014.940.","journal-title":"JAMA Surg"},{"issue":"3","key":"5406_CR7","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1097\/TA.0000000000001333","volume":"82","author":"JW Cannon","year":"2017","unstructured":"Cannon JW, Khan MA, Raja AS, et al. Damage control resuscitation in patients with severe traumatic hemorrhage: a practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg. 2017;82(3):605\u201317. https:\/\/doi.org\/10.1097\/TA.0000000000001333.","journal-title":"J Trauma Acute Care Surg"},{"key":"5406_CR8","unstructured":"Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Web-based Injury Statistics Query and Reporting System (WISQARS). Accessed May 16, 2022. www.cdc.gov\/injury\/wisqars."},{"issue":"6","key":"5406_CR9","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1097\/SHK.0000000000000482","volume":"44","author":"S Pati","year":"2015","unstructured":"Pati S, Pilia M, Grimsley JM, et al. Cellular therapies in trauma and critical care medicine: forging new frontiers. Shock. 2015;44(6):505\u201323. https:\/\/doi.org\/10.1097\/SHK.0000000000000482.","journal-title":"Shock"},{"issue":"2","key":"5406_CR10","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/stem.2551","volume":"35","author":"MA Matthay","year":"2017","unstructured":"Matthay MA, Pati S, Lee JW. Concise review: mesenchymal stem (stromal) cells: biology and preclinical evidence for therapeutic potential for organ dysfunction following trauma or sepsis. Stem Cells. 2017;35(2):316\u201324. https:\/\/doi.org\/10.1002\/stem.2551.","journal-title":"Stem Cells"},{"issue":"9","key":"5406_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025171","volume":"6","author":"S Pati","year":"2011","unstructured":"Pati S, Gerber MH, Menge TD, et al. Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. PLoS ONE. 2011;6(9): e25171. https:\/\/doi.org\/10.1371\/journal.pone.0025171.","journal-title":"PLoS ONE"},{"issue":"3","key":"5406_CR12","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1097\/TA.0000000000003487","volume":"92","author":"M Barry","year":"2022","unstructured":"Barry M, Trivedi A, Pathipati P, et al. Mesenchymal stem cell extracellular vesicles mitigate vascular permeability and injury in the small intestine and lung in a mouse model of hemorrhagic shock and trauma. J Trauma Acute Care Surg. 2022;92(3):489\u201398. https:\/\/doi.org\/10.1097\/TA.0000000000003487.","journal-title":"J Trauma Acute Care Surg"},{"issue":"1","key":"5406_CR13","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1186\/s13287-021-02505-4","volume":"12","author":"C Aussel","year":"2021","unstructured":"Aussel C, Baudry N, Grosbot M, et al. IL-1\u03b2 primed mesenchymal stromal cells moderate hemorrhagic shock-induced organ injuries. Stem Cell Res Ther. 2021;12(1):438. https:\/\/doi.org\/10.1186\/s13287-021-02505-4.","journal-title":"Stem Cell Res Ther"},{"key":"5406_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.811164","volume":"12","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Zhang X, Zhang H, et al. Mesenchymal stem cells derived extracellular vesicles alleviate traumatic hemorrhagic shock induced hepatic injury. Front Immunol. 2021;12: 811164. https:\/\/doi.org\/10.3389\/fimmu.2021.811164.","journal-title":"Front Immunol"},{"issue":"2","key":"5406_CR15","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.jss.2015.06.023","volume":"199","author":"AV Gore","year":"2015","unstructured":"Gore AV, Bible LE, Livingston DH, Mohr AM, Sifri ZC. Mesenchymal stem cells reverse trauma and hemorrhagic shock-induced bone marrow dysfunction. J Surg Res. 2015;199(2):615\u201321. https:\/\/doi.org\/10.1016\/j.jss.2015.06.023.","journal-title":"J Surg Res"},{"key":"5406_CR16","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fimmu.2014.00148","volume":"5","author":"E Eggenhofer","year":"2014","unstructured":"Eggenhofer E, Luk F, Dahlke MH, Hoogduijn MJ. The life and fate of mesenchymal stem cells. Front Immunol. 2014;5:148. https:\/\/doi.org\/10.3389\/fimmu.2014.00148.","journal-title":"Front Immunol"},{"issue":"5","key":"5406_CR17","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/mt.2015.44","volume":"23","author":"S Rani","year":"2015","unstructured":"Rani S, Ryan AE, Griffin MD, Ritter T. Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications. Mol Ther. 2015;23(5):812\u201323. https:\/\/doi.org\/10.1038\/mt.2015.44.","journal-title":"Mol Ther"},{"issue":"9","key":"5406_CR18","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41580-019-0158-7","volume":"20","author":"G Raposo","year":"2019","unstructured":"Raposo G, Stahl PD. Extracellular vesicles: a new communication paradigm? Nat Rev Mol Cell Biol. 2019;20(9):509\u201310. https:\/\/doi.org\/10.1038\/s41580-019-0158-7.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"9","key":"5406_CR19","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/sctm.18-0226","volume":"8","author":"G Baek","year":"2019","unstructured":"Baek G, Choi H, Kim Y, Lee HC, Choi C. Mesenchymal stem cell-derived extracellular vesicles as therapeutics and as a drug delivery platform. Stem Cells Transl Med. 2019;8(9):880\u20136. https:\/\/doi.org\/10.1002\/sctm.18-0226.","journal-title":"Stem Cells Transl Med"},{"key":"5406_CR20","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000003164","author":"M Barry","year":"2021","unstructured":"Barry M, Trivedi A, Miyazawa BY, et al. Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma. J Trauma Acute Care Surg. 2021. https:\/\/doi.org\/10.1097\/TA.0000000000003164.","journal-title":"J Trauma Acute Care Surg"},{"issue":"2","key":"5406_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1097\/TA.0000000000001744","volume":"84","author":"DR Potter","year":"2018","unstructured":"Potter DR, Miyazawa BY, Gibb SL, et al. Mesenchymal stem cell-derived extracellular vesicles attenuate pulmonary vascular permeability and lung injury induced by hemorrhagic shock and trauma. J Trauma Acute Care Surg. 2018;84(2):245\u201356. https:\/\/doi.org\/10.1097\/TA.0000000000001744.","journal-title":"J Trauma Acute Care Surg"},{"issue":"3","key":"5406_CR22","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1007\/s12035-017-0509-3","volume":"55","author":"H Kumar","year":"2018","unstructured":"Kumar H, Jo MJ, Choi H, et al. Matrix metalloproteinase-8 inhibition prevents disruption of blood-spinal cord barrier and attenuates inflammation in rat model of spinal cord injury. Mol Neurobiol. 2018;55(3):2577\u201390. https:\/\/doi.org\/10.1007\/s12035-017-0509-3.","journal-title":"Mol Neurobiol"},{"issue":"2","key":"5406_CR23","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1093\/cvr\/cvq105","volume":"87","author":"DO Bates","year":"2010","unstructured":"Bates DO. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res. 2010;87(2):262\u201371. https:\/\/doi.org\/10.1093\/cvr\/cvq105.","journal-title":"Cardiovasc Res"},{"issue":"21","key":"5406_CR24","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1089\/scd.2013.0193","volume":"22","author":"MJ Hoogduijn","year":"2013","unstructured":"Hoogduijn MJ, Roemeling-van Rhijn M, Engela AU, et al. Mesenchymal stem cells induce an inflammatory response after intravenous infusion. Stem Cells Dev. 2013;22(21):2825\u201335. https:\/\/doi.org\/10.1089\/scd.2013.0193.","journal-title":"Stem Cells Dev"},{"issue":"7","key":"5406_CR25","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/s41419-022-05034-x","volume":"13","author":"M Kou","year":"2022","unstructured":"Kou M, Huang L, Yang J, et al. Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool? Cell Death Dis. 2022;13(7):580. https:\/\/doi.org\/10.1038\/s41419-022-05034-x.","journal-title":"Cell Death Dis"},{"issue":"1","key":"5406_CR26","doi-asserted-by":"publisher","first-page":"e2062","DOI":"10.1038\/cddis.2015.327","volume":"7","author":"F Gao","year":"2016","unstructured":"Gao F, Chiu SM, Motan DA, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016;7(1):e2062. https:\/\/doi.org\/10.1038\/cddis.2015.327.","journal-title":"Cell Death Dis"},{"issue":"9","key":"5406_CR27","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nrd.2016.278","volume":"16","author":"P Saharinen","year":"2017","unstructured":"Saharinen P, Eklund L, Alitalo K. Therapeutic targeting of the angiopoietin-TIE pathway. Nat Rev Drug Discov. 2017;16(9):635\u201361. https:\/\/doi.org\/10.1038\/nrd.2016.278.","journal-title":"Nat Rev Drug Discov"},{"issue":"8","key":"5406_CR28","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1002\/sctm.17-0278","volume":"7","author":"S Hu","year":"2018","unstructured":"Hu S, Park J, Liu A, et al. Mesenchymal stem cell microvesicles restore protein permeability across primary cultures of injured human lung microvascular endothelial cells. Stem Cells Transl Med. 2018;7(8):615\u201324. https:\/\/doi.org\/10.1002\/sctm.17-0278.","journal-title":"Stem Cells Transl Med"},{"issue":"1","key":"5406_CR29","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s13287-017-0662-7","volume":"8","author":"H Wang","year":"2017","unstructured":"Wang H, Zheng R, Chen Q, Shao J, Yu J, Hu S. Mesenchymal stem cells microvesicles stabilize endothelial barrier function partly mediated by hepatocyte growth factor (HGF). Stem Cell Res Ther. 2017;8(1):211. https:\/\/doi.org\/10.1186\/s13287-017-0662-7.","journal-title":"Stem Cell Res Ther"},{"issue":"161","key":"5406_CR30","doi-asserted-by":"publisher","first-page":"161ra50","DOI":"10.1126\/scitranslmed.3004660","volume":"4","author":"T Menge","year":"2012","unstructured":"Menge T, Zhao Y, Zhao J, et al. Mesenchymal stem cells regulate blood-brain barrier integrity through TIMP3 release after traumatic brain injury. Sci Transl Med. 2012;4(161):161ra50. https:\/\/doi.org\/10.1126\/scitranslmed.3004660.","journal-title":"Sci Transl Med"},{"issue":"3","key":"5406_CR31","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/stem.2298","volume":"34","author":"JD Anderson","year":"2016","unstructured":"Anderson JD, Johansson HJ, Graham CS, et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-KappaB signaling. Stem Cells. 2016;34(3):601\u201313. https:\/\/doi.org\/10.1002\/stem.2298.","journal-title":"Stem Cells"},{"issue":"1","key":"5406_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10565-005-0085-6","volume":"21","author":"Y Sambuy","year":"2005","unstructured":"Sambuy Y, De Angelis I, Ranaldi G, Scarino ML, Stammati A, Zucco F. The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol. 2005;21(1):1\u201326. https:\/\/doi.org\/10.1007\/s10565-005-0085-6.","journal-title":"Cell Biol Toxicol"},{"issue":"3","key":"5406_CR33","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nbt.2816","volume":"32","author":"JA Ankrum","year":"2014","unstructured":"Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014;32(3):252\u201360. https:\/\/doi.org\/10.1038\/nbt.2816.","journal-title":"Nat Biotechnol"},{"issue":"1","key":"5406_CR34","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/TA.0000000000002916","volume":"90","author":"JE Schucht","year":"2021","unstructured":"Schucht JE, Matheson PJ, Harbrecht BG, Bond L, Ashkettle GR, Smith JW. Plasma resuscitation with adjunctive peritoneal resuscitation reduces ischemia-induced intestinal barrier breakdown following hemorrhagic shock. J Trauma Acute Care Surg. 2021;90(1):27\u201334. https:\/\/doi.org\/10.1097\/TA.0000000000002916.","journal-title":"J Trauma Acute Care Surg"},{"issue":"2","key":"5406_CR35","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/SHK.0b013e31817fc310","volume":"31","author":"G Thuijls","year":"2009","unstructured":"Thuijls G, de Haan JJ, Derikx JP, et al. Intestinal cytoskeleton degradation precedes tight junction loss following hemorrhagic shock. Shock. 2009;31(2):164\u20139. https:\/\/doi.org\/10.1097\/SHK.0b013e31817fc310.","journal-title":"Shock"},{"issue":"3","key":"5406_CR36","doi-asserted-by":"publisher","first-page":"G621","DOI":"10.1152\/ajpgi.00177.2003","volume":"285","author":"R Yang","year":"2003","unstructured":"Yang R, Han X, Uchiyama T, et al. IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice. Am J Physiol Gastrointest Liver Physiol. 2003;285(3):G621\u20139. https:\/\/doi.org\/10.1152\/ajpgi.00177.2003.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"1","key":"5406_CR37","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.arcmed.2020.08.006","volume":"52","author":"DE Rodr\u00edguez-Fuentes","year":"2021","unstructured":"Rodr\u00edguez-Fuentes DE, Fern\u00e1ndez-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Salda\u00f1a HA. Mesenchymal stem cells current clinical applications: a systematic review. Arch Med Res. 2021;52(1):93\u2013101. https:\/\/doi.org\/10.1016\/j.arcmed.2020.08.006.","journal-title":"Arch Med Res"},{"issue":"4","key":"5406_CR38","doi-asserted-by":"publisher","first-page":"20S","DOI":"10.1111\/trf.13566","volume":"56","author":"MC Herzig","year":"2016","unstructured":"Herzig MC, Cap AP. Challenges in translating mesenchymal stem cell therapies for trauma and critical care. Transfusion. 2016;56(4):20S-S25. https:\/\/doi.org\/10.1111\/trf.13566.","journal-title":"Transfusion"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-024-05406-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-024-05406-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-024-05406-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T11:08:06Z","timestamp":1718968086000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-024-05406-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,21]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["5406"],"URL":"https:\/\/doi.org\/10.1186\/s12967-024-05406-1","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,21]]},"assertion":[{"value":"17 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal studies were performed with approval of the Institutional Animal Care and Use Committee (IACUC) at UCSF. The experiments were conducted in compliance with the ARRIVE guidelines for animal models and the National Institutes of Health (NIH) guidelines on the use of laboratory animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"588"}}