{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T10:14:34Z","timestamp":1769595274434,"version":"3.49.0"},"reference-count":84,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01NS090962, R01NS102395 and R21NS109575."],"award-info":[{"award-number":["R01NS090962, R01NS102395 and R21NS109575."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ischemic brain injury represents a major cause of death worldwide with limited treatment options with a narrow therapeutic window. Accordingly, novel treatments that extend the treatment from the early neuroprotective stage to the late regenerative phase may accommodate a much larger number of stroke patients. To this end, stem cell-based regenerative therapies may address this unmet clinical need. Several stem cell therapies have been tested as potentially exhibiting the capacity to regenerate the stroke brain. Based on the long track record and safety profile of transplantable stem cells for hematologic diseases, bone marrow-derived mesenchymal stromal cells or mesenchymal stromal cells have been widely tested in stroke animal models and have reached clinical trials. However, despite the translational promise of MSCs, probing cell function remains to be fully elucidated. Recognizing the multi-pronged cell death and survival processes that accompany stroke, here we review the literature on MSC definition, characterization, and mechanism of action in an effort to gain a better understanding towards optimizing its applications and functional outcomes in stroke.<\/jats:p>","DOI":"10.3390\/cells11061013","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:25:00Z","timestamp":1647811500000},"page":"1013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Mesenchymal Stromal Cells in Ischemic Brain Injury"],"prefix":"10.3390","volume":"11","author":[{"given":"Beverly","family":"Brooks","sequence":"first","affiliation":[{"name":"Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Ebedes","sequence":"additional","affiliation":[{"name":"Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahsan","family":"Usmani","sequence":"additional","affiliation":[{"name":"Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin Vega","family":"Gonzales-Portillo","sequence":"additional","affiliation":[{"name":"Universidad Peruana de Ciencias Aplicadas, Prolongaci\u00f3n Primavera 2390, Lima 15023, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Gonzales-Portillo","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Florida, 945 Center Dr, Gainesville, FL 32611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-9782","authenticated-orcid":false,"given":"Cesario V.","family":"Borlongan","sequence":"additional","affiliation":[{"name":"Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12974-019-1516-2","article-title":"Neuroinflammation: Friend and foe for ischemic stroke","volume":"16","author":"Jayaraj","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s13287-020-01762-z","article-title":"Stem cell-based therapies for ischemic stroke: A systematic review and meta-analysis of clinical trials","volume":"11","author":"Li","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/S1474-4422(19)30415-6","article-title":"Advances and challenges in stroke rehabilitation","volume":"19","author":"Stinear","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1161\/STROKEAHA.117.018288","article-title":"Intra-Arterial Delivery of Cell Therapies for Stroke","volume":"49","author":"Guzman","year":"2018","journal-title":"Stroke"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/JCN.0b013e318197a6a5","article-title":"Introduction to stem cell therapy","volume":"94","author":"Biehl","year":"2009","journal-title":"J. Cardiovasc. Nurs."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13287-019-1165-5","article-title":"Stem cells: Past, present, and future","volume":"10","author":"Zakrzewski","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.reth.2020.01.004","article-title":"Advances in regenerative therapy: A review of the literature and future directions","volume":"14","author":"Ntege","year":"2020","journal-title":"Regen. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1002\/jnr.22054","article-title":"Stem cell-based cell therapy in neurological diseases: A review","volume":"87","author":"Kim","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrd.2016.245","article-title":"Induced pluripotent stem cell technology: A decade of progress","volume":"16","author":"Shi","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev.cellbio.22.010305.104357","article-title":"Epidermal stem cells of the skin","volume":"22","author":"Blanpain","year":"2006","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/cphy.c140068","article-title":"Satellite Cells and Skeletal Muscle Regeneration","volume":"5","author":"Dumont","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11842","DOI":"10.1038\/s41598-019-48156-7","article-title":"Muscle satellite cells and impaired late stage regeneration in different murine models for muscular dystrophies","volume":"9","author":"Ribeiro","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1097\/01.moh.0000245697.54887.6f","article-title":"Mesenchymal stromal cells","volume":"13","author":"Keating","year":"2006","journal-title":"Curr. Opin. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1365-2133.2006.07357.x","article-title":"Differentiation potential of human embryonic mesenchymal stem cells for skin-related tissue","volume":"155","author":"Wu","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"650664","DOI":"10.3389\/fcell.2021.650664","article-title":"The Current Status of Mesenchymal Stromal Cells: Controversies, Unresolved Issues and Some Promising Solutions to Improve Their Therapeutic Efficacy","volume":"9","author":"Bueren","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"933","DOI":"10.2217\/rme.10.72","article-title":"Mesenchymal stem cells for the treatment of neurodegenerative disease","volume":"5","author":"Joyce","year":"2010","journal-title":"Regen. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fcell.2020.00258","article-title":"Senescence in Mesenchymal Stem Cells: Functional Alterations, Molecular Mechanisms, and Rejuvenation Strategies","volume":"8","author":"Liu","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1186\/s13287-020-01855-9","article-title":"Mesenchymal stromal cell therapies: Immunomodulatory properties and clinical progress","volume":"11","author":"Wu","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3960\/jslrt.50.79","article-title":"Mesenchymal stromal cells for graft-versus-host disease: Basic aspects and clinical outcomes","volume":"50","author":"Sato","year":"2010","journal-title":"J. Clin. Exp. Hematop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"609277","DOI":"10.3389\/fimmu.2020.609277","article-title":"Key Metabolic Pathways in MSC-Mediated Immunomodulation: Implications for the Prophylaxis and Treatment of Graft Versus Host Disease","volume":"11","author":"Burnham","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.3389\/fimmu.2020.01338","article-title":"Mesenchymal Stromal Cells for Graft Versus Host Disease: Mechanism-Based Biomarkers","volume":"11","author":"Cheung","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000496809","article-title":"Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease","volume":"46","author":"Elgaz","year":"2019","journal-title":"Trans. Med. Hemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1007\/s00415-020-10138-5","article-title":"Mesenchymal stem cell therapy for ischemic stroke: A look into treatment mechanism and therapeutic potential","volume":"268","author":"Li","year":"2021","journal-title":"J. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9929128","DOI":"10.1155\/2021\/9929128","article-title":"Strategies to Improve the Efficiency of Transplantation with Mesenchymal Stem Cells for the Treatment of Ischemic Stroke: A Review of Recent Progress","volume":"2021","author":"Li","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"628940","DOI":"10.3389\/fncel.2021.628940","article-title":"Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges","volume":"15","author":"Li","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1177\/0271678X18776802","article-title":"The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke","volume":"38","author":"Cunningham","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1002\/jcp.24981","article-title":"Paracrine Factors Secreted by MSCs Promote Astrocyte Survival Associated with GFAP Downregulation after Ischemic Stroke via p38 MAPK and JNK","volume":"230","author":"Huang","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3389\/fneur.2019.00332","article-title":"Cell-Based Therapies for Stroke: Promising Solution or Dead End? Mesenchymal Stem Cells and Comorbidities in Preclinical Stroke Research","volume":"10","author":"Diekhorst","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.arcmed.2020.08.006","article-title":"Mesenchymal Stem Cells Current Clinical Applications: A Systematic Review","volume":"52","author":"Caplan","year":"2021","journal-title":"Arch. Med. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13287-019-1224-y","article-title":"Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies","volume":"10","author":"Noronha","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.stem.2018.05.004","article-title":"Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities","volume":"22","author":"Galipeau","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13045-021-01037-x","article-title":"Challenges and advances in clinical applications of mesenchymal stromal cells","volume":"14","author":"Zhou","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1136\/bmj.319.7220.1308","article-title":"Stem cell technology. Interview by Abi Berger","volume":"319","author":"Fontes","year":"1999","journal-title":"BMJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3389\/fbioe.2020.00148","article-title":"Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?","volume":"8","author":"Casamitjana","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000290897","article-title":"Mesenchymal Stem or Stromal Cells: Toward a Better Understanding of Their Biology?","volume":"37","author":"Lindner","year":"2010","journal-title":"Transfus. Med. Hemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/14653240500319234","article-title":"Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement","volume":"7","author":"Horwitz","year":"2005","journal-title":"Cytotherapy"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jozkowiak, M., Hutchings, G., Jankowski, M., Kulcenty, K., Mozdziak, P., Kempisty, B., Spaczynski, R.Z., and Piotrowska-Kempisty, H. (2020). The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs\u2014A Review Based on Cellular and Molecular Knowledge. Cells, 9.","DOI":"10.3390\/cells9061418"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1002\/jcb.23287","article-title":"Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation","volume":"112","author":"Lin","year":"2011","journal-title":"J. Cell Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1186\/s13287-020-01823-3","article-title":"Multiomics global landscape of stemness-related gene clusters in adipose-derived mesenchymal stem cells","volume":"11","author":"Lu","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13045-020-00994-z","article-title":"Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1161\/CIRCULATIONAHA.109.898312","article-title":"Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice","volume":"121","author":"Lian","year":"2010","journal-title":"Circulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6354","DOI":"10.7150\/thno.34008","article-title":"Transplantation of induced pluripotent stem cell-derived mesenchymal stem cells improved erectile dysfunction induced by cavernous nerve injury","volume":"9","author":"Chen","year":"2019","journal-title":"Theranostics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.7150\/thno.30487","article-title":"Characterization and Therapeutic Application of Mesenchymal Stem Cells with Neuromesodermal Origin from Human Pluripotent Stem Cells","volume":"9","author":"Wang","year":"2019","journal-title":"Theranostics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5841716","DOI":"10.1155\/2017\/5841716","article-title":"SIRT3 Enhances Mesenchymal Stem Cell Longevity and Differentiation","volume":"2017","author":"Denu","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/rheumatology\/kem206","article-title":"Human bone marrow mesenchymal stem cells in vivo","volume":"47","author":"Jones","year":"2008","journal-title":"Rheumatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"591","DOI":"10.5966\/sctm.2015-0176","article-title":"Massive Clonal Selection and Transiently Contributing Clones during Expansion of Mesenchymal Stem Cell Cultures Revealed by Lentiviral RGB-Barcode Technology","volume":"5","author":"Selich","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s12974-019-1571-8","article-title":"Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles","volume":"16","author":"Dabrowska","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1177\/0963689718795424","article-title":"Transplanting Mesenchymal Stem Cells for Treatment of Ischemic Stroke","volume":"27","author":"Wang","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1002\/term.2914","article-title":"Mesenchymal stem cells: Cell therapy and regeneration potential","volume":"13","author":"Brown","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fcell.2017.00051","article-title":"Stem Cell-Induced Biobridges as Possible Tools to Aid Neuroreconstruction after CNS Injury","volume":"5","author":"Lee","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1515\/revneuro-2019-0002","article-title":"Mesenchymal stem cell therapy for the treatment of traumatic brain injury: Progress and prospects","volume":"30","author":"Das","year":"2019","journal-title":"Rev. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4103\/bc.bc_7_21","article-title":"Cell-based treatment for perinatal hypoxic-ischemic encephalopathy","volume":"7","author":"Park","year":"2021","journal-title":"Brain Circ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fncel.2017.00055","article-title":"MSCs-Derived Exosomes and Neuroinflammation, Neurogenesis and Therapy of Traumatic Brain Injury","volume":"11","author":"Yang","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.5966\/sctm.2015-0078","article-title":"Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression","volume":"4","author":"Doeppner","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2147\/JN.S119874","article-title":"Mesenchymal stromal cell therapy in ischemic stroke","volume":"4","author":"Zhang","year":"2016","journal-title":"J. Neurorestoratol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1161\/STROKEAHA.117.018292","article-title":"Exosome Therapy for Stroke","volume":"49","author":"Chen","year":"2018","journal-title":"Stroke"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Eleuteri, S., and Fierabracci, A. (2019). Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184597"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kawabori, M., Shichinohe, H., Kuroda, S., and Houkin, K. (2020). Clinical trials of stem cell therapy for cerebral ischemic stroke. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197380"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8249","DOI":"10.1002\/jcp.27669","article-title":"Interaction between mesenchymal stromal cell-derived extracellular vesicles and immune cells by distinct protein content","volume":"234","author":"Mardpour","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/sj.jcbfm.9600311","article-title":"Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke","volume":"27","author":"Shen","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1080\/00207454.2019.1633315","article-title":"Intra-arterial stem cell therapy modulates neuronal calcineurin and confers neuroprotection after ischemic stroke","volume":"129","author":"Saraf","year":"2019","journal-title":"Int. J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9923566","DOI":"10.1155\/2021\/9923566","article-title":"Progress in Mesenchymal Stem Cell Therapy for Ischemic Stroke","volume":"2021","author":"Guo","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_63","first-page":"058","article-title":"Stem cell therapy for ischemic stroke: From bench to bedside","volume":"4","author":"Pryck","year":"2018","journal-title":"Int. J. Crit. Care Emerg. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/scrt434","article-title":"Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model","volume":"5","author":"Karlupia","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"40758","DOI":"10.1038\/srep40758","article-title":"Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia","volume":"7","author":"Argibay","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"621645","DOI":"10.3389\/fcell.2021.621645","article-title":"Are We Ready for Cell Therapy to Treat Stroke?","volume":"9","author":"Barcia","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1161\/STROKEAHA.119.026318","article-title":"Phase I\/II study of safety and preliminary efficacy of intravenous allogeneic mesenchymal stem cells in chronic stroke","volume":"50","author":"Levy","year":"2019","journal-title":"Stroke"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1007\/s12975-016-0490-6","article-title":"Recent Advances in Stem Cell-Based Therapeutics for Stroke","volume":"7","author":"Napoli","year":"2016","journal-title":"Transl. Stroke Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0041-1","article-title":"Interleukin-1 receptor antagonist-mediated neuroprotection by umbilical cord-derived mesenchymal stromal cells following transplantation into a rodent stroke model","volume":"50","author":"Oh","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1177\/0963689717728936","article-title":"Human umbilical cord mesenchymal stem cells preserve adult newborn neurons and reduce neurological injury after cerebral ischemia by reducing the number of hypertrophic microglia\/macrophages","volume":"26","author":"Lin","year":"2017","journal-title":"Cell Transplant."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8657173","DOI":"10.1155\/2016\/8657173","article-title":"Increasing Dose of Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled Analysis of Two Clinical Trials","volume":"2016","author":"Moniche","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1212\/WNL.0000000000000278","article-title":"Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke","volume":"82","author":"Vu","year":"2014","journal-title":"Neurology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"eaba6884","DOI":"10.1126\/sciadv.aba6884","article-title":"Shattering barriers toward clinically meaningful MSC therapies","volume":"6","author":"Levy","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Pinho, A.G., Cibr\u00e3o, J.R., Silva, N.A., Monteiro, S., and Salgado, A.J. (2020). Cell Secretome: Basic Insights and Therapeutic Opportunities for CNS Disorders. Pharmaceuticals, 13.","DOI":"10.3390\/ph13020031"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13287-020-1560-y","article-title":"Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke","volume":"11","author":"Cunningham","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/jcp.26931","article-title":"Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats","volume":"234","author":"Jiang","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13287-017-0531-4","article-title":"Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory and pro-trophic phenotype in vitro","volume":"8","author":"Cunningham","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1111\/jcmm.13492","article-title":"Preconditioning influences mesenchymal stem cell properties in vitro and in vivo","volume":"22","author":"Hu","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Miceli, V., Bulati, M., Iannolo, G., Zito, G., Gallo, A., and Conaldi, P.G. (2021). Therapeutic Properties of Mesenchymal Stromal\/Stem Cells: The Need of Cell Priming for Cell-Free Therapies in Regenerative Medicine. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020763"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9176357","DOI":"10.1155\/2016\/9176357","article-title":"Spheroid Culture of Mesenchymal Stem Cells","volume":"2016","author":"Cesarz","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fcell.2020.00149","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles: Challenges in Clinical Applications","volume":"8","author":"Gowen","year":"2020","journal-title":"Front. Cell. Dev. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"997","DOI":"10.3389\/fbioe.2020.00997","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation","volume":"8","author":"Maumus","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.jcyt.2019.08.002","article-title":"Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT\u00ae) Mesenchymal Stromal Cell committee position statement on nomenclature","volume":"21","author":"Viswanathan","year":"2019","journal-title":"Cytotherapy"},{"key":"ref_84","first-page":"157","article-title":"Mesenchymal stem cells in the treatment of ischemic stroke: Progress and possibilities","volume":"3","author":"Doeppner","year":"2010","journal-title":"Stem Cells Cloning"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/6\/1013\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:37:55Z","timestamp":1760135875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/6\/1013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":84,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cells11061013"],"URL":"https:\/\/doi.org\/10.3390\/cells11061013","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]}}}