{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:57:50Z","timestamp":1791644270175,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that significantly impacts children's physical and mental health, yet effective pharmacological treatments remain limited. The primary objective of this study was to investigate the therapeutic effects of human umbilical cord blood mesenchymal stem cells (hUC\u2010MSCs) on ASD, evaluate the safety profile of hUC\u2010MSCs, and elucidate their underlying mechanisms and functional roles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we utilized the offspring of pregnant mice exposed to valproic acid (VPA) as an animal model of ASD. At the beginning of 5 weeks of age, 5 \u00d7 10\n                      <jats:sup>5<\/jats:sup>\n                      hUC\u2010MSCs were administered into the lateral ventricles to evaluate their safety profile and elucidate their potential roles and underlying mechanisms. Specifically, we first monitored the growth and overall health status of the mice following hUC\u2010MSC treatment and assessed potential toxic effects by performing H&amp;E staining on major organs. Second, behavioral analyses were conducted to examine changes in social interaction, repetitive and stereotyped behaviors, and anxiety\u2010like behaviors in young mice before and after hUC\u2010MSC intervention. Finally, the mechanisms underlying the therapeutic effects of hUC\u2010MSCs in ASD were explored using techniques such as RT\u2010PCR, Western blot analysis, brain tissue staining, and neuron culture experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we demonstrate that hUC\u2010MSCs effectively mitigate behavioral abnormalities in a VPA\u2010induced mouse model of autism without notable adverse effects. Mechanistically, hUC\u2010MSC treatment promotes cortical neuronal dendritic development and restores the phosphorylation levels of insulin\u2010like growth factor 1 receptor (IGF\u20101R) and protein kinase B (Akt). Furthermore, mRNA expression of synaptic plasticity\u2010associated genes GAP\u201043 and SYP, as well as the anti\u2010inflammatory cytokine IL\u201010, was significantly upregulated, while the expression of proapoptotic genes Bax and Caspase\u20103, along with pro\u2010inflammatory cytokines IL\u20106 and IL\u20101\u03b2, was markedly suppressed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that hUC\u2010MSCs may exert neuroprotective effects by modulating the IGF\u20101\/Akt signaling pathway, promoting neuronal development, reducing neuroinflammation, and inhibiting apoptosis, ultimately alleviating core ASD\u2010like symptoms. The therapeutic benefits may stem from paracrine factors secreted by hUC\u2010MSCs or their ability to regulate gene expression linked to neuronal development. Our study provides new insights into ASD pathogenesis and highlights the potential of hUC\u2010MSCs as a novel stem cell\u2010based therapy for ASD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71335","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:32:35Z","timestamp":1775017955000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Umbilical Cord Blood Mesenchymal Stem Cells Ameliorate Autism\u2010Like Behaviors in a Valproic Acid\u2010Induced Mouse Model via the IGF\u20101\/Akt Signaling Pathway"],"prefix":"10.1002","volume":"16","author":[{"given":"Jie","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"},{"name":"Institute of Pediatric Research Hubei University of Medicine  Shiyan Hubei China"},{"name":"Hubei Provincial Clinical Research Center For Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hujing","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"},{"name":"Institute of Pediatric Research Hubei University of Medicine  Shiyan Hubei China"},{"name":"Department of Pediatrics, First Clinical School Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhoujing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhen","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"},{"name":"Institute of Pediatric Research Hubei University of Medicine  Shiyan Hubei China"},{"name":"Department of Pediatrics, First Clinical School Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaowei","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taihe Hospital, Hubei University of Medicine  Shiyan Hubei China"},{"name":"Institute of Pediatric Research Hubei University of Medicine  Shiyan Hubei China"},{"name":"Hubei Provincial Clinical Research Center For Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010024\u201009451\u20103"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2021.676303"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2022.06.023"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.01.015"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134726"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14030677"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.23661"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019\u20103447"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858418811787"},{"issue":"6","key":"e_1_2_12_11_1","first-page":"3890","article-title":"MSC: Immunoregulatory Effects, Roles on Neutrophils and Evolving Clinical Potentials","volume":"11","author":"Joel M. D. M.","year":"2019","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787\u2010025\u201001641\u20100"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229\u2010022\u201000493\u20107"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2002032"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010023\u201002738\u20105"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689719837897"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010024\u201009292\u20100"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104579"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.897398"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000713"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104486"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.18773\/austprescr.2020.054"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00450"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24031819"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30030740"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.12.035"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1483574"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.71335","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.71335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T08:23:46Z","timestamp":1780907026000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.71335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/brb3.71335"],"URL":"https:\/\/doi.org\/10.1002\/brb3.71335","archive":["Portico"],"relation":{},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"assertion":[{"value":"2025-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71335"}}