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Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) represent a promising therapeutic approach due to their immunomodulatory, neuroprotective, and regenerative properties. However, the lack of comprehensive efficacy data using GMP-grade cells, uncertainty regarding optimal dosing, and incomplete understanding of their mechanisms have hindered clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A T10-level SCI model was established in 50 Sprague\u2012Dawley rats using Allen\u2019s weight-drop method. The animals were randomly divided into five groups: Sham, Model, Solvent, Low-dose (1\u2009\u00d7\u200910\u2077 cells\/kg), and High-dose (3\u2009\u00d7\u200910\u2077 cells\/kg). GMP-grade human UC-MSCs were administered intravenously on post-injury days 3 and 7. A comprehensive evaluation was performed using BBB scoring for locomotor function, MRI for lesion volume assessment, histopathological examination (H&amp;E and Nissl staining), ELISA for serum cytokine quantification, immunofluorescence for GFAP and GAP-43 expression, single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs), in\n                      <jats:italic>vivo<\/jats:italic>\n                      UC-MSCs tracking, and sRNA sequencing of human UC-MSC-derived exosomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The high-dose UC-MSC treatment demonstrated significant therapeutic effects, including: improved hindlimb motor function (BBB scores from days 7 to 21), reduced spinal cord lesion volume, attenuated pathological damage (decreased cavity formation, preserved neuronal morphology, increased neuron density), and suppressed acute inflammation (reduced TNF-\u03b1 and IL-6 levels). Additionally, high-dose treatment decreased astrocyte activation (reduced GFAP expression), enhanced neuronal plasticity (increased GAP-43), modulated immune cell populations (increased na\u00efve CD4\u207a\/CD8\u207a T cells, decreased memory B cells), and downregulated SCI-activated genes (including Kras and Nfkb1). In vivo tracking revealed initial pulmonary accumulation of UC-MSCs followed by clearance within 3 days. sRNA sequencing of human UC-MSC-derived exosomes identified several human-derived miRNAs (hsa-miR-21-5p, hsa-let-7a-5p, hsa-miR-10b-5p, hsa-miR-451a, and hsa-miR-10a-5p) potentially involved in the repair process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GMP-grade human UC-MSCs exert therapeutic effects in SCI through multiple mechanisms, including anti-inflammatory actions, inhibition of glial scarring, neuroprotection, and immune modulation. The high-dose regimen (3\u2009\u00d7\u200910\u2077 cells\/kg) demonstrated superior efficacy across functional, structural, and molecular endpoints. This study provides critical preclinical evidence supporting the clinical application of UC-MSCs for SCI treatment and elucidates their underlying therapeutic mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08373-x","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:23:44Z","timestamp":1781072624000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Translational potential of GMP-grade human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in traumatic spinal cord injury: a preclinical study in rat"],"prefix":"10.1186","volume":"24","author":[{"given":"Zhibo","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuling","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongjin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjian","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"8373_CR1","doi-asserted-by":"publisher","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","volume":"3","author":"CS Ahuja","year":"2017","unstructured":"Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, et al. 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