PMID- 38056156 OWN - NLM STAT- MEDLINE DCOM- 20240108 LR - 20240116 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 692 DP - 2024 Jan 15 TI - HGF secreted by hUC-MSCs mitigates neuronal apoptosis to repair the injured spinal cord via phosphorylation of Akt/FoxO3a pathway. PG - 149321 LID - S0006-291X(23)01415-8 [pii] LID - 10.1016/j.bbrc.2023.149321 [doi] AB - Spinal cord injury (SCI) can cause severe and permanent neurological damage, and neuronal apoptosis could inhibit functional recovery of damaged spinal cord greatly. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have great potential to repair SCI because of a series of advantages, including inhibition of neuronal apoptosis and multiple differentiation. The former may play an important role. However, the detailed regulatory mechanism associated with the inhibition of neuronal apoptosis after hUC-MSCs administration has not been elucidated. In this study, proteomics analysis of precious human cerebrospinal fluid (CSF) samples collected from SCI subjects receiving hUC-MSCs delivery indicated that hepatocyte growth factor (HGF) is largely involved in SCI repair. Furthermore, overexpression of HGF derived from hUC-MSCs could decrease reactive oxygen species to prevent neuron apoptosis to the maximum, and thus lead to significant recovery of spinal cord dysfunction. Moreover, HGF could promote phosphorylation of Akt/FoxO3a pathway to decrease reactive oxygen species to reduce neuron apoptosis. For the first time, our research revealed that HGF secreted by hUC-MSCs inhibits neuron apoptosis by phosphorylation of Akt/FoxO3a to repair SCI. This study provides important clues associated with drug selection for the effective treatment of SCI in humans. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Cai, Chaoyang AU - Cai C AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. FAU - Li, Hong AU - Li H AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. FAU - Tian, Zhenming AU - Tian Z AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. FAU - Liang, Qian AU - Liang Q AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. FAU - Shen, Ruoqi AU - Shen R AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. FAU - Wu, Zizhao AU - Wu Z AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. Electronic address: wuzzh3@mail.sysu.edu.cn. FAU - Liu, Bin AU - Liu B AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. Electronic address: liubin6@mail.sysu.edu.cn. FAU - Yang, Yang AU - Yang Y AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; National Medical Products Administration (NMPA), Key Laboratory for Quality Research and Evaluation of Cell Products, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong Province, China. Electronic address: yangyang3@mail.sysu.edu.cn. LA - eng PT - Journal Article DEP - 20231128 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 0 (Reactive Oxygen Species) RN - 0 (HGF protein, human) SB - IM MH - Humans MH - Hepatocyte Growth Factor/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Phosphorylation MH - Reactive Oxygen Species/metabolism MH - Umbilical Cord MH - Apoptosis MH - *Spinal Cord Injuries/metabolism MH - *Mesenchymal Stem Cells MH - *Mesenchymal Stem Cell Transplantation OTO - NOTNLM OT - Apoptosis OT - Hepatocyte growth factor (HGF) OT - Human umbilical cord mesenchymal stem cells (hUC-MSCs) OT - Neuron OT - Spinal cord injury (SCI) COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2023/12/07 00:42 MHDA- 2024/01/08 06:42 CRDT- 2023/12/06 18:07 PHST- 2023/09/11 00:00 [received] PHST- 2023/11/16 00:00 [revised] PHST- 2023/11/22 00:00 [accepted] PHST- 2024/01/08 06:42 [medline] PHST- 2023/12/07 00:42 [pubmed] PHST- 2023/12/06 18:07 [entrez] AID - S0006-291X(23)01415-8 [pii] AID - 10.1016/j.bbrc.2023.149321 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2024 Jan 15;692:149321. doi: 10.1016/j.bbrc.2023.149321. Epub 2023 Nov 28.