{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:57:50Z","timestamp":1790269070357,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To investigate the therapeutic mechanisms of miR\u20109\u20105p\u2010overexpressing human umbilical cord mesenchymal stromal cells (hUC\u2010MSCs) in neonatal rat models of hypoxic\u2010ischemic brain damage (HIBD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fresh neonatal umbilical cords were collected to isolate and culture human umbilical cord mesenchymal stromal cells (hUC\u2010MSCs). Recombinant adenovirus was used to amplify miR\u20109\u20105p and transduce hUC\u2010MSCs, generating miR\u20109\u20105p\u2010overexpressing cells. Functional assessments included: ELISA to evaluate secretory function (e.g., neurotrophic and anti\u2010inflammatory factors), real\u2010time cell analysis to measure proliferation capacity, Transwell and Dunn chamber assays to assess chemotactic migration ability. Healthy 7\u2010day\u2010old Sprague\u2010Dawley (SD) rats of both sexes were randomly allocated into four groups (\n                      <jats:italic>n<\/jats:italic>\n                      = 12\/group, with 4 rats per group assigned to TTC staining, Western blot, or Morris water maze assay, respectively): Sham\u2010operated control group (mock surgery), Hypoxic\u2010ischemic brain damage (HIBD) model group, miR\u20109\u20105p\u2010hUC\u2010MSCs treatment group, and Adenovirus\u2010transduced hUC\u2010MSCs (Ad\u2010hUC\u2010MSCs) treatment group. The HIBD model was induced in groups 2\u20134. At 24 h post\u2010modeling, 1\u00d710\n                      <jats:sup>6<\/jats:sup>\n                      miR\u20109\u20105p\u2010hUC\u2010MSCs or Ad\u2010hUC\u2010MSCs were transplanted into the left lateral ventricle (injured side) of the pups. Neurological function was evaluated 48 h later using righting reflex tests for short\u2010term neurobehavioral assessment. Subsequently, 4 rats per group were sacrificed for 2,3,5\u2010triphenyltetrazolium chloride (TTC) staining to quantify cerebral infarction volume. Hippocampal tissues from another 4 rats per group were analyzed by Western blot for Beclin\u20102 and Caspase\u20103 protein expression. The remaining 4 rats per group underwent 28\u2010day Morris water maze testing for long\u2010term neurobehavioral evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Spindle\u2010shaped and polygonal adherent cells emerged within 3\u20135 days following umbilical cord tissue block inoculation, with flow cytometric analysis confirming their identity as mesenchymal stromal cells (MSCs). Compared to the Ad\u2010hUC\u2010MSCs treatment group, miR\u20109\u20105p enhanced the secretion of neuroreparative and anti\u2010inflammatory factors (e.g., NGF, BDNF, IL\u20106) in hUC\u2010MSCs while suppressing pro\u2010inflammatory cytokines (e.g., IL\u20101, IL\u20102) (p\u00a0&lt; 0.05). Furthermore, miR\u20109\u20105p significantly promoted hUC\u2010MSCs proliferation and augmented the chemotactic migratory capacity of miR\u20109\u20105p\u2010hUC\u2010MSCs. At 48 h post\u2010transplantation in the miR\u20109\u20105p\u2010hUC\u2010MSCs group, the sham\u2010operated controls showed no detectable cerebral infarction, whereas the model group exhibited distinct pale infarct foci occupying 33.15%\u00a0\u00b1\u00a04.38% of total brain volume (vs.\u00a0controls,\u00a0p\u00a0&lt;\u00a00.05), indicating severe cerebral injury. Both miR\u20109\u20105p\u2010hUC\u2010MSCs and Ad\u2010hUC\u2010MSCs treatments markedly reduced infarct volumes to 14.85% \u00b1 2.79% and 19.11% \u00b1 4.57%, respectively, with the miR\u20109\u20105p\u2010hUC\u2010MSCs group demonstrating a statistically superior therapeutic effect compared to Ad\u2010hUC\u2010MSCs (p\u00a0&lt; 0.05). Transplantation of either Ad\u2010hUC\u2010MSCs or miR\u20109\u20105p\u2010hUC\u2010MSCs significantly improved short\u2010 and long\u2010term neurobehavioral outcomes in hypoxic\u2010ischemic brain damage (HIBD) rats. At 48 h post\u2010HIBD induction, upregulated expression of Beclin\u20102 and Caspase\u20103 proteins was observed in brain tissue. Notably, these elevated protein levels were attenuated following treatment with miR\u20109\u20105p\u2010hUC\u2010MSCs or Ad\u2010hUC\u2010MSCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MiR\u20109\u20105p enhances the secretion of immunomodulatory factors and improves the migratory and proliferative capacities of hUC\u2010MSCs. Overexpression of miR\u20109\u20105p promotes in vivo homing of hUC\u2010MSCs, which mitigate cerebral injury and exert neuroprotective and reparative effects through dual mechanisms: modulating immune responses and providing neurotrophic support. Furthermore, hUC\u2010MSCs significantly reduce cerebral infarct volume in hypoxic\u2010ischemic brain damage (HIBD) rats and downregulate levels of apoptotic proteins (Beclin\u20102 and Caspase\u20103) in brain tissue, demonstrating potent cerebroprotective effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71282","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:31:58Z","timestamp":1772965918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic Effect of Human Umbilical Cord Mesenchymal Stromal Cells Loaded With miR\u20109\u20105p on Hypoxic\u2010Ischemic Brain Damage in Neonatal Rats"],"prefix":"10.1002","volume":"16","author":[{"given":"Bin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatrics Weiyuan County People's Hospital  Neijiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research Guizhou Medical University  Guiyang Guizhou China"},{"name":"Children's Medical Center Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medical Science Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The First People's Hospital of Guiyang  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences Guizhou Medical University  Guiyang Guizhou China"},{"name":"Guizhou Guizhong Biotechnology Co., Ltd  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research Guizhou Medical University  Guiyang Guizhou China"},{"name":"Department of Pharmacology, School of Basic Medical Sciences Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuxian","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailiang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of General Surgery Dongguan Dalang Hospital  Dongguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1242936"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12010186"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2018.02.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13642"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61577-8"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113430"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.176003"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e31742"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v14.i3.245"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-021-10217-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-020-00276-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00952-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-022-10369-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04228-y"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215299"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.1c02530"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1268990"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-04454-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03499-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1400533"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxac042"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25137235"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179672"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-018-1052-5"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.12.034"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689719874769"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.035"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.129"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-022-03776-w"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012561"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAT.0000000000001938"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-024-00349-z"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71282","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.71282","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:47:06Z","timestamp":1787600826000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.71282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/brb3.71282"],"URL":"https:\/\/doi.org\/10.1002\/brb3.71282","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.71282\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.71282\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.71282\/v1\/decision1","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71282"}}