{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:55:43Z","timestamp":1781643343423,"version":"3.54.5"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH235"],"award-info":[{"award-number":["ZR2023MH235"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Development Program of Jinan Municipal Health Commission","award":["2025102001"],"award-info":[{"award-number":["2025102001"]}]},{"name":"Science and Technology Development Program of Jinan Municipal Health Commission","award":["2024202001"],"award-info":[{"award-number":["2024202001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071383"],"award-info":[{"award-number":["82071383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371392"],"award-info":[{"award-number":["82371392"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2020KH007"],"award-info":[{"award-number":["ZR2020KH007"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\u201cTaishan Scholar Distinguished Expert Program\u201d of Shandong Province","award":["tstp20231257"],"award-info":[{"award-number":["tstp20231257"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal cord injury (SCI) causes severe energy metabolism dysfunction, hindering neuronal survival and recovery. Adipose tissue-derived stromal cells (ADSCs) have neuroprotective potential, but their role in regulating neuronal energy metabolism and the underlying mechanisms remain unclear. This study aimed to investigate whether ADSCs are capable of restoring neuronal glycolysis through the FOXK1-HK2 signaling pathway, thereby replenishing the energy supply and facilitating tissue regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed rat and cell models of SCI to observe the effects of ADSCs on glycolytic metabolism and apoptosis. Transcriptome sequencing identified glycolysis-related differentially expressed genes. Lactate detection and Seahorse assays were used to quantify glycolytic activity. Dual-luciferase reporter assays verified the FOXK1-HK2 regulatory relationship. Cut&amp;Run assay provided direct evidence of FOXK1 binding to the HK2 promoter. Behavioral tests, histopathological staining and immunofluorescence were used to evaluate in vivo functional recovery and tissue repair. FOXK1 knockdown confirmed its role in the ADSC-mediated pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that ADSCs exerted multiple protective and regulatory effects on neurons and motor function. Specifically, they strongly inhibited neuronal oxidative stress, protected mitochondria, and promoted neuronal metabolic reprogramming. Additionally, ADSCs increased glycolytic activity and lactate production, which further contributed to promoting neuronal survival and the recovery of hindlimb motor function. Blocking TGF-\u03b21 signaling abrogated ADSC-induced activation of the FOXK1-HK2 axis and subsequent enhancement of glycolysis, confirming TGF-\u03b21 as a critical paracrine mediator. Through interaction with HK2, FOXK1 plays a critical role in modulating glycolysis. Dual-luciferase reporter and Cut&amp;Run assays confirmed that FOXK1 regulates the HK2 promoter, thereby increasing its transcriptional activity. The inhibition of FOXK1 expression resulted in suppressed HK2 expression, reduced glycolytic flux, and weakened the neuroprotective effects of ADSCs on SCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ADSCs are considered a potential option for SCI treatment, and their therapeutic effects are closely related to the FOXK1\/HK2 axis, which mediates ADSCs\u2019 regulation of neuronal glycolytic metabolism to exert protective and reparative functions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-07958-w","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:25:36Z","timestamp":1773746736000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose tissue-derived stromal cells enhance glycolytic metabolism in injured nerve cells via the FOXK1-HK2 axis for spinal cord injury repair"],"prefix":"10.1186","volume":"24","author":[{"given":"Fang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanxiang","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuepeng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuzhu","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"7958_CR1","doi-asserted-by":"crossref","unstructured":"Chen L, Zhourui W, Liqiang Z, Jingliang S, Xiao H, Wei X, Yilong R, Xingfei Z, Weihong G, Kunshan Z, Jiping L, Runzhi H, Jing Y, et al. Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury. Signal Transduct Target Ther. 2022;7(1).","DOI":"10.1038\/s41392-022-00885-4"},{"key":"7958_CR2","unstructured":"Henri L, Andrea G, Valeria S, Felix M, Serpil K, Nadine I, Molywan V, Olivier F, Cathal H, Salif K, Jimmy R, Thibault C, Laure C, et al. Walking naturally after spinal cord injury using a brain-spine interface. Nature. 2023;618(7963)."},{"key":"7958_CR3","doi-asserted-by":"crossref","unstructured":"Tao Y, Wenzhao L, Minyu Z, Xiaocheng W, Bing W, Yuanjin Z. Biomimetic multichannel silk nerve conduits with multicellular spatiotemporal distributions for spinal cord injury repair. 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ADSC-Exos enhance functional recovery after spinal cord injury by inhibiting ferroptosis and promoting the survival and function of endothelial cells through the NRF2\/SLC7A11\/GPX4 pathway. Biomed Pharmacother. 2024;172(0).","DOI":"10.1016\/j.biopha.2024.116225"},{"key":"7958_CR18","doi-asserted-by":"crossref","unstructured":"Jad EM, Hiba F, Rahaf AS, Ahmad A, Mohamed A-S, Wassim A-K. Adipose-derived stem cell therapy in spinal cord injury. Cells. 2024;13(17).","DOI":"10.3390\/cells13171505"},{"key":"7958_CR19","doi-asserted-by":"crossref","unstructured":"Zhilai Z, Xiaobo T, Biling M, Huali X, Li Z, Lishan H, Shun Y, Zixiang H, Yeyang W, Huan X, Liwei X, Hui Z. Adipose mesenchymal stem cell transplantation alleviates spinal cord injury-induced neuroinflammation partly by suppressing the Jagged1\/Notch pathway. 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Additionally, all the animal experiments were conducted with the approval of the Jinan Central Hospital Experimental Animal Welfare Ethics Review Committee (approval number: JNCHIACUC2024-24). All experimental procedures were performed in accordance with the ethical guidelines of the Experimental Animal Welfare Ethics Review Committee of Jinan Central Hospital and the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All the authors reviewed and approved the final version of the manuscript for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that there are no competing interests in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"582"}}