{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:55:51Z","timestamp":1790898951228,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"North Tech Foundation","award":["R6SB-1-8"],"award-info":[{"award-number":["R6SB-1-8"]}]},{"name":"North Tech Foundation","award":["22H03188"],"award-info":[{"award-number":["22H03188"]}]},{"name":"North Tech Foundation","award":["B7335R"],"award-info":[{"award-number":["B7335R"]}]},{"name":"North Tech Foundation","award":["B9260L"],"award-info":[{"award-number":["B9260L"]}]},{"name":"JSPS KAKENHI grant","award":["R6SB-1-8"],"award-info":[{"award-number":["R6SB-1-8"]}]},{"name":"JSPS KAKENHI grant","award":["22H03188"],"award-info":[{"award-number":["22H03188"]}]},{"name":"JSPS KAKENHI grant","award":["B7335R"],"award-info":[{"award-number":["B7335R"]}]},{"name":"JSPS KAKENHI grant","award":["B9260L"],"award-info":[{"award-number":["B9260L"]}]},{"name":"RR&amp;D and BLR&amp;D Services of the U.S. Department of Veterans Affairs","award":["R6SB-1-8"],"award-info":[{"award-number":["R6SB-1-8"]}]},{"name":"RR&amp;D and BLR&amp;D Services of the U.S. Department of Veterans Affairs","award":["22H03188"],"award-info":[{"award-number":["22H03188"]}]},{"name":"RR&amp;D and BLR&amp;D Services of the U.S. Department of Veterans Affairs","award":["B7335R"],"award-info":[{"award-number":["B7335R"]}]},{"name":"RR&amp;D and BLR&amp;D Services of the U.S. Department of Veterans Affairs","award":["B9260L"],"award-info":[{"award-number":["B9260L"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal cord injury (SCI) disrupts the blood\u2013spinal cord barrier (BSCB) exacerbating damage by allowing harmful substances and immune cells to infiltrate spinal neural tissues from the vasculature. This leads to inflammation, oxidative stress, and impaired axonal regeneration. The BSCB, essential for maintaining spinal cord homeostasis, is structurally similar to the blood\u2013brain barrier. Its restoration is a key therapeutic target for improving outcomes in SCI. Mesenchymal stromal\/stem cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have gained attention for their regenerative, immunomodulatory, and anti-inflammatory properties in promoting BSCB repair. MSCs enhance BSCB integrity by improving endothelial\u2013pericyte association, restoring tight junction proteins, and reducing inflammation. MSC-EVs, which deliver bioactive molecules, replicate many of MSCs\u2019 therapeutic effects, and offer a promising cell-free alternative. Preclinical studies have shown that both MSCs and MSC-EVs can reduce BSCB permeability, promote vascular stability, and support functional recovery. While MSC therapy is advancing in clinical trials, MSC-EV therapies require further optimization in terms of production, dosing, and delivery protocols. Despite these challenges, both therapeutic approaches represent significant potential for treating SCI by targeting BSCB repair and improving patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms252413460","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T04:14:52Z","timestamp":1734322492000},"page":"13460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Mesenchymal Stem Cells and Their Extracellular Vesicles: Therapeutic Mechanisms for Blood\u2013Spinal Cord Barrier Repair Following Spinal Cord Injury"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3155-5116","authenticated-orcid":false,"given":"Masahito","family":"Nakazaki","sequence":"first","affiliation":[{"name":"Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan"},{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA"},{"name":"Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5555-4495","authenticated-orcid":false,"given":"Takahiro","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Lankford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA"},{"name":"Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2210-0497","authenticated-orcid":false,"given":"Ryosuke","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan"},{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA"},{"name":"Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3780-7719","authenticated-orcid":false,"given":"Jeffery D.","family":"Kocsis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA"},{"name":"Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Honmou","sequence":"additional","affiliation":[{"name":"Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan"},{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA"},{"name":"Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1089\/neu.2020.7413","article-title":"Blood-Spinal Cord Barrier in Spinal Cord Injury: A Review","volume":"38","author":"Jin","year":"2021","journal-title":"J. Neurotrauma"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1089\/neu.2013.3034","article-title":"Characterization of Vascular Disruption and Blood-Spinal Cord Barrier Permeability following Traumatic Spinal Cord Injury","volume":"31","author":"Figley","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1006\/exnr.1996.0196","article-title":"A quantitative spatial analysis of the blood-spinal cord barrier. I. Permeability changes after experimental spinal contusion injury","volume":"142","author":"Popovich","year":"1996","journal-title":"Exp. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.expneurol.2015.03.001","article-title":"Diffuse and persistent blood-spinal cord barrier disruption after contusive spinal cord injury rapidly recovers following intravenous infusion of bone marrow mesenchymal stem cells","volume":"267","author":"Matsushita","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"589","DOI":"10.18388\/abp.2016_1272","article-title":"Gastrodin ameliorates spinal cord injury via antioxidant and anti-inflammatory effects","volume":"63","author":"Du","year":"2016","journal-title":"Acta Biochim. Pol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12137","DOI":"10.1002\/jev2.12137","article-title":"Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF-beta upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury","volume":"10","author":"Nakazaki","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.neuroscience.2016.08.037","article-title":"Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury","volume":"335","author":"Morita","year":"2016","journal-title":"Neuroscience"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1284","DOI":"10.1002\/ctm2.1284","article-title":"Human mesenchymal stem-derived extracellular vesicles improve body growth and motor function following severe spinal cord injury in rat","volume":"13","author":"Nakazaki","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.molmed.2012.02.003","article-title":"Mesenchymal stem cells: Therapeutic outlook for stroke","volume":"18","author":"Honmou","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cytogfr.2009.10.002","article-title":"Mechanisms involved in the therapeutic properties of mesenchymal stem cells","volume":"20","author":"Fontes","year":"2009","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/mt.2015.44","article-title":"Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications","volume":"23","author":"Rani","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/stem.2575","article-title":"Concise Review: MSC-Derived Exosomes for Cell-Free Therapy","volume":"35","author":"Phinney","year":"2017","journal-title":"Stem Cells"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1609206","DOI":"10.1080\/20013078.2019.1609206","article-title":"Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications","volume":"8","author":"Witwer","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.addr.2012.07.001","article-title":"Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery","volume":"65","author":"Yeo","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lankford, K.L., Arroyo, E.J., Nazimek, K., Bryniarski, K., Askenase, P.W., and Kocsis, J.D. (2018). Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190358"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nri2567","article-title":"Membrane vesicles as conveyors of immune responses","volume":"9","author":"Ostrowski","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Muniz-Garcia, A., Wilm, B., Murray, P., and Cross, M.J. (2022). Extracellular Vesicles from Human Umbilical Cord-Derived MSCs Affect Vessel Formation In Vitro and Promote VEGFR2-Mediated Cell Survival. Cells, 11.","DOI":"10.3390\/cells11233750"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1302\/2046-3758.105.BJR-2020-0020.R1","article-title":"Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4\/WNT5A axis","volume":"10","author":"Jia","year":"2021","journal-title":"Bone Joint Res."},{"key":"ref_22","first-page":"2523","article-title":"A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury","volume":"6","author":"Wang","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"B\u00f6rger, V., Bremer, M., Ferrer-Tur, R., Gockeln, L., Stambouli, O., Becic, A., and Giebel, B. (2017). Mesenchymal Stem\/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071450"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41419-022-05034-x","article-title":"Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: A next generation therapeutic tool?","volume":"13","author":"Kou","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1242\/jcs.110.14.1603","article-title":"Occludin as a possible determinant of tight junction permeability in endothelial cells","volume":"110","author":"Hirase","year":"1997","journal-title":"J. Cell Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"29745","DOI":"10.1074\/jbc.273.45.29745","article-title":"The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton","volume":"273","author":"Fanning","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.1091\/mbc.e09-04-0320","article-title":"ZO-1 stabilizes the tight junction solute barrier through coupling to the perijunctional cytoskeleton","volume":"20","author":"Fanning","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/1097-0177(200007)218:3<472::AID-DVDY1008>3.0.CO;2-#","article-title":"N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken","volume":"218","author":"Gerhardt","year":"2000","journal-title":"Dev. Dyn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1126\/science.1203165","article-title":"A pericyte origin of spinal cord scar tissue","volume":"333","author":"Goritz","year":"2011","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nn.4288","article-title":"Pericytes of the neurovascular unit: Key functions and signaling pathways","volume":"19","author":"Sweeney","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.neuroscience.2019.04.018","article-title":"Intravenous infusion of mesenchymal stem cells improves impaired cognitive function in a cerebral small vessel disease model","volume":"408","author":"Nakazaki","year":"2019","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature09522","article-title":"Pericytes regulate the blood-brain barrier","volume":"468","author":"Armulik","year":"2010","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/(SICI)1097-4547(19980915)53:6<637::AID-JNR1>3.0.CO;2-6","article-title":"Role of the CNS microvascular pericyte in the blood-brain barrier","volume":"53","author":"Balabanov","year":"1998","journal-title":"J. Neurosci. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuron.2010.09.043","article-title":"Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging","volume":"68","author":"Bell","year":"2010","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.tips.2016.12.001","article-title":"Brain Pericytes As Mediators of Neuroinflammation","volume":"38","author":"Rustenhoven","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0165-3806(87)90075-7","article-title":"Astrocyte-mediated induction of tight junctions in brain capillary endothelium: An efficient in vitro model","volume":"433","author":"Arthur","year":"1987","journal-title":"Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/brain\/awab311","article-title":"Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis","volume":"145","author":"Salman","year":"2022","journal-title":"Brain J. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13272","DOI":"10.1523\/JNEUROSCI.3337-11.2011","article-title":"Adenosine receptor signaling modulates permeability of the blood-brain barrier","volume":"31","author":"Carman","year":"2011","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.neulet.2016.12.049","article-title":"Selective induction of P-glycoprotein at the CNS barriers during symptomatic stage of an ALS animal model","volume":"639","author":"Chan","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"917","DOI":"10.3171\/2016.8.JNS16240","article-title":"Intravenous infusion of mesenchymal stem cells inhibits intracranial hemorrhage after recombinant tissue plasminogen activator therapy for transient middle cerebral artery occlusion in rats","volume":"127","author":"Nakazaki","year":"2017","journal-title":"J. Neurosurg."},{"key":"ref_41","first-page":"A32","article-title":"Pericytes Promote Dissociation of the Neovasculature Through CXCR3 Signaling","volume":"22","author":"Bodnar","year":"2014","journal-title":"Wound Repair Regen."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00401-018-1893-0","article-title":"Targeting pericytes for therapeutic approaches to neurological disorders","volume":"136","author":"Cheng","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.1038\/s41467-018-07036-w","article-title":"Dynamic control of proinflammatory cytokines Il-1beta and Tnf-alpha by macrophages in zebrafish spinal cord regeneration","volume":"9","author":"Tsarouchas","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Versele, R., Sevin, E., Gosselet, F., Fenart, L., and Candela, P. (2022). TNF-\u03b1 and IL-1\u03b2 Modulate Blood-Brain Barrier Permeability and Decrease Amyloid-\u03b2 Peptide Efflux in a Human Blood-Brain Barrier Model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810235"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2795090","DOI":"10.1155\/2016\/2795090","article-title":"The Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases","volume":"2016","author":"Tan","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13435","DOI":"10.1523\/JNEUROSCI.3257-09.2009","article-title":"Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord","volume":"29","author":"Kigerl","year":"2009","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1016\/j.biomaterials.2014.02.012","article-title":"The role of macrophage phenotype in vascularization of tissue engineering scaffolds","volume":"35","author":"Spiller","year":"2014","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"27457","DOI":"10.1021\/acsami.3c00489","article-title":"Heparin Affinity-Based IL-4 Delivery to Modulate Macrophage Phenotype and Endothelial Cell Activity In Vitro","volume":"15","author":"Zhang","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.3171\/2018.5.JNS18140","article-title":"Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction","volume":"131","author":"Namioka","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/sj.jcbfm.9600475","article-title":"Angiopoietin1\/Tie2 and VEGF\/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke","volume":"27","author":"Zacharek","year":"2007","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"147296","DOI":"10.1016\/j.brainres.2021.147296","article-title":"Intravenous infusion of mesenchymal stem cells delays disease progression in the SOD1G93A transgenic amyotrophic lateral sclerosis rat model","volume":"1757","author":"Magota","year":"2021","journal-title":"Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s13287-015-0180-4","article-title":"Mesenchymal stem cells stabilize the blood-brain barrier through regulation of astrocytes","volume":"6","author":"Park","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lu, Y., Zhou, Y., Zhang, R., Wen, L., Wu, K., Li, Y., Yao, Y., Duan, R., and Jia, Y. (2019). Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00209"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6490","DOI":"10.1007\/s12035-021-02565-w","article-title":"Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Attenuate Blood-Spinal Cord Barrier Disruption via the TIMP2\/MMP Pathway After Acute Spinal Cord Injury","volume":"58","author":"Wang","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Menezes, K., Rosa, B.G., Freitas, C., da Cruz, A.S., de Siqueira Santos, R., Nascimento, M.A., Alves, D.V.L., Bonamino, M., Rossi, M.I., and Borojevic, R. (2020). Human mesenchymal stromal\/stem cells recruit resident pericytes and induce blood vessels maturation to repair experimental spinal cord injury in rats. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-76290-0"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"194","DOI":"10.4103\/1673-5374.314323","article-title":"Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis","volume":"17","author":"Zhou","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12974-015-0284-x","article-title":"The inhibitory effect of mesenchymal stem cell on blood-brain barrier disruption following intracerebral hemorrhage in rats: Contribution of TSG-6","volume":"12","author":"Chen","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/mt.2011.211","article-title":"Mesenchymal stem\/stromal cells (MSCs): Role as guardians of inflammation","volume":"20","author":"Prockop","year":"2012","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1182\/blood-2010-12-327353","article-title":"Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2\/NF-kappaB signaling in resident macrophages","volume":"118","author":"Choi","year":"2011","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1002\/stem.1400","article-title":"Concise review: Two negative feedback loops place mesenchymal stem\/stromal cells at the center of early regulators of inflammation","volume":"31","author":"Prockop","year":"2013","journal-title":"Stem Cells"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.actbio.2022.10.022","article-title":"Mesenchymal stem cell-derived extracellular vesicles attenuate tPA-induced blood-brain barrier disruption in murine ischemic stroke models","volume":"154","author":"Qiu","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1007\/s00701-022-05369-6","article-title":"The inflammatory response and blood-spinal cord barrier integrity in traumatic spinal cord injury: A prospective pilot study","volume":"164","author":"Wichmann","year":"2022","journal-title":"Acta Neurochir."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12974-023-02787-w","article-title":"Pathological hemodynamic changes and leukocyte transmigration disrupt the blood-spinal cord barrier after spinal cord injury","volume":"20","author":"Zhou","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5713","DOI":"10.2147\/JIR.S329864","article-title":"Neuroinflammation and Modulation Role of Natural Products After Spinal Cord Injury","volume":"14","author":"Wu","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1089\/neu.2011.2109","article-title":"Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury","volume":"29","author":"Nakajima","year":"2012","journal-title":"J. Neurotrauma"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tmrv.2015.11.004","article-title":"Unraveling the Mesenchymal Stromal Cells\u2019 Paracrine Immunomodulatory Effects","volume":"30","author":"Fontaine","year":"2016","journal-title":"Transfus. Med. Rev."},{"key":"ref_67","first-page":"516","article-title":"Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory\/suppressive phenotype","volume":"90","author":"Maccario","year":"2005","journal-title":"Haematologica"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Neyrolles, O., Maggini, J., Mirkin, G., Bognanni, I., Holmberg, J., Piazz\u00f3n, I.M., Nepomnaschy, I., Costa, H., Ca\u00f1ones, C., and Raiden, S. (2010). Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009252"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Vasandan, A.B., Jahnavi, S., Shashank, C., Prasad, P., Kumar, A., and Prasanna, S.J. (2016). Human Mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE(2)-dependent mechanism. Sci. Rep., 6.","DOI":"10.1038\/srep38308"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Wang, X., Gu, H., Qin, D., Yang, L., Huang, W., Essandoh, K., Wang, Y., Caldwell, C.C., Peng, T., and Zingarelli, B. (2015). Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Polymicrobial Sepsis. Sci. Rep., 5.","DOI":"10.1038\/srep13721"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1016\/j.ymthe.2020.04.020","article-title":"Comprehensive Molecular Profiles of Functionally Effective MSC-Derived Extracellular Vesicles in Immunomodulation","volume":"28","author":"Kim","year":"2020","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/cvr\/cvz040","article-title":"Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization","volume":"115","author":"Zhao","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1002\/stem.2564","article-title":"Exosomal miR-146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin-1beta-Primed Mesenchymal Stem Cells Against Sepsis","volume":"35","author":"Song","year":"2017","journal-title":"Stem Cells"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"106565","DOI":"10.1016\/j.clineuro.2021.106565","article-title":"Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series","volume":"203","author":"Honmou","year":"2021","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Gimona, M., Pachler, K., Laner-Plamberger, S., Schallmoser, K., and Rohde, E. (2017). Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061190"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:52:48Z","timestamp":1760115168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":75,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413460"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413460","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,16]]}}}