PMID- 38242900 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240122 IS - 2057-3995 (Electronic) IS - 2057-3995 (Linking) VI - 9 IP - 1 DP - 2024 Jan 20 TI - hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-kappaB signaling in an NMO mouse model. PG - 4 LID - 10.1038/s41536-024-00349-z [doi] LID - 4 AB - Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin alphavbeta3/NF-kappaB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO. CI - (c) 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Xu, Huiming AU - Xu H AUID- ORCID: 0009-0004-3242-4550 AD - Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China. FAU - Jiang, Wei AU - Jiang W AUID- ORCID: 0000-0002-8315-339X AD - Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China. FAU - Li, Xuejia AU - Li X AUID- ORCID: 0000-0002-2925-5088 AD - Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China. FAU - Jiang, Jiaohua AU - Jiang J AUID- ORCID: 0009-0009-5464-7057 AD - Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China. FAU - Afridi, Shabbir Khan AU - Afridi SK AUID- ORCID: 0000-0003-1633-4470 AD - Faculty of Biological Sciences, School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK. FAU - Deng, Longhui AU - Deng L AUID- ORCID: 0009-0002-5881-5598 AD - Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China. FAU - Li, Rui AU - Li R AUID- ORCID: 0000-0002-1932-3737 AD - Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China. FAU - Luo, Ermei AU - Luo E AD - Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China. FAU - Zhang, Zhaoqing AU - Zhang Z AD - Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China. FAU - Huang, Yu-Wen Alvin AU - Huang YA AUID- ORCID: 0000-0003-4082-8008 AD - Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship 15 Street, Providence, RI, 02903, USA. FAU - Cui, Yaxiong AU - Cui Y AUID- ORCID: 0000-0002-3063-0324 AD - State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, Beijing Advanced Innovation Center for Structural Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China. FAU - So, Kwok-Fai AU - So KF AUID- ORCID: 0000-0003-4039-4246 AD - Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China. FAU - Chen, Haijia AU - Chen H AUID- ORCID: 0009-0000-5631-9713 AD - Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China. chenhaijia@vip.sina.com. FAU - Qiu, Wei AU - Qiu W AUID- ORCID: 0000-0002-0880-958X AD - Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China. qiuwei120@vip.163.com. FAU - Tang, Changyong AU - Tang C AUID- ORCID: 0000-0001-7048-108X AD - Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China. tangchy23@mail.sysu.edu.cn. LA - eng GR - 201909020006/Guangzhou Science and Technology Program key projects/ GR - 2022A1515012398/Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ GR - 82071344/National Natural Science Foundation of China (National Science Foundation of China)/ PT - Journal Article DEP - 20240120 PL - United States TA - NPJ Regen Med JT - NPJ Regenerative medicine JID - 101699846 PMC - PMC10798960 COIS- The authors declare no competing interests. EDAT- 2024/01/20 05:42 MHDA- 2024/01/20 05:43 PMCR- 2024/01/20 CRDT- 2024/01/19 23:16 PHST- 2023/04/26 00:00 [received] PHST- 2024/01/09 00:00 [accepted] PHST- 2024/01/20 05:43 [medline] PHST- 2024/01/20 05:42 [pubmed] PHST- 2024/01/19 23:16 [entrez] PHST- 2024/01/20 00:00 [pmc-release] AID - 10.1038/s41536-024-00349-z [pii] AID - 349 [pii] AID - 10.1038/s41536-024-00349-z [doi] PST - epublish SO - NPJ Regen Med. 2024 Jan 20;9(1):4. doi: 10.1038/s41536-024-00349-z.