PMID- 35057811 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20220321 IS - 1477-3155 (Electronic) IS - 1477-3155 (Linking) VI - 20 IP - 1 DP - 2022 Jan 20 TI - Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages. PG - 38 LID - 10.1186/s12951-021-01236-1 [doi] LID - 38 AB - Osteoarthritis (OA) is a degenerative illness that greatly impacts the life quality of patients. Currently, the therapeutic approaches for OA are very limited in clinical. The extracellular vesicles (EVs) derived from different mesenchymal stem cells displayed a prominent therapeutic effect on OA. But most EVs have limited resources and the risks of host rejection, immunological response, and etc. Human umbilical cord mesenchymal stem cells (hUCMSCs) hold the advantages of easy availability, minimal immune rejection, and excellent immunomodulatory effects, although hUCMSCs-EVs have seldom been applied in OA. Herein, we investigated the potential immunomodulatory and anti-inflammatory effects of hUCMSCs-EVs on the treatment of OA. In our results, the treatment of hUCMSCs-EVs promoted the polarization of M2-type macrophages and the expression of anti-inflammation-related cytokines (IL-10). Notably, the supernate of M2 macrophages induced by hUCMSCs-EVs inhibited the level of inflammation-associated factors in OA chondrocytes caused by IL-1beta. Further, injection of hUCMSCs-EVs in the articular lumen ameliorated progression of OA and exerted chondroprotective potential based on the OA joint model created by the surgical transection of the anterior cruciate ligament (ACLT). In addition, we found five highly enriched miRNAs in hUCMSCs-EVs, including has-miR-122-5p, has-miR-148a-3p, has-miR-486-5p, has-miR-let-7a-5p, and has-miR-100-5p by High-throughput sequencing of miRNAs, with targeted genes mainly enriched in the PI3K-Akt signaling pathway. Furthermore, we also detected the protein abundance of hUCMSCs-EVs using liquidation chromatography with tandem quadrupole mass spectrometry (LC-MS/MS) analysis. Thus, our study indicates that hUCMSCs-EVs can alleviate cartilage degradation during the OA progression, mechanically may through delivering key proteins and modulating the PI3K-Akt signaling pathway mediated by miRNAs to promote polarization of M2 macrophage, exhibiting potent immunomodulatory potential. The current findings suggest that hUCMSCs-EVs might serve as a new reagent for the therapy of OA. CI - (c) 2022. The Author(s). FAU - Li, Kanglu AU - Li K AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. AD - Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. FAU - Yan, Guohua AU - Yan G AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. AD - Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. FAU - Huang, Hanji AU - Huang H AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. FAU - Zheng, Mingjun AU - Zheng M AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. AD - Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. FAU - Ma, Ke AU - Ma K AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China. FAU - Cui, Xiaofei AU - Cui X AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. AD - Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. FAU - Lu, Dejie AU - Lu D AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. AD - Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. FAU - Zheng, Li AU - Zheng L AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. zhengli224@163.com. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. zhengli224@163.com. AD - International Joint Laboratory of Ministry of Education for Regeneration of Bone and Soft Tissues, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. zhengli224@163.com. FAU - Zhu, Bo AU - Zhu B AUID- ORCID: 0000-0001-5856-6320 AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. gxzyxyzhobo@163.com. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. gxzyxyzhobo@163.com. AD - Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. gxzyxyzhobo@163.com. FAU - Cheng, Jianwen AU - Cheng J AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. csgkswk@126.com. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. csgkswk@126.com. AD - Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. csgkswk@126.com. FAU - Zhao, Jinmin AU - Zhao J AD - Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, 530021, China. AD - Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. AD - International Joint Laboratory of Ministry of Education for Regeneration of Bone and Soft Tissues, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. AD - Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China. LA - eng GR - 2018YFC1105900/National Key R&D Program of China/ GR - 81972120/National Natural Science Fundation of China/ GR - GuikeAD19254003/Guangxi Key Research and Development Plan/ GR - GuikeAA19254002/Guangxi Science and Technology Major Project/ GR - 81960400/National Natural Science Foundation of China/ GR - 82160418/National Natural Science Foundation of China/ GR - 2019GXNSFAA185004/Guangxi Natural Science Foundation Program/ PT - Journal Article DEP - 20220120 PL - England TA - J Nanobiotechnology JT - Journal of nanobiotechnology JID - 101152208 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cell Extracts) RN - 0 (Immunomodulating Agents) SB - IM MH - Animals MH - *Anti-Inflammatory Agents/chemistry/pharmacology MH - Cell Extracts/chemistry/pharmacology MH - Extracellular Vesicles/*chemistry MH - Humans MH - Immunomodulating Agents/chemistry/pharmacology MH - Macrophages/drug effects MH - Male MH - Mesenchymal Stem Cells/*cytology MH - Osteoarthritis/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Umbilical Cord/*cytology PMC - PMC8771624 OTO - NOTNLM OT - Extracellular vesicles OT - Human umbilical cord mesenchymal stem cells OT - Macrophage OT - MicroRNA OT - Osteoarthritis COIS- The authors declare that they have no competing interests. EDAT- 2022/01/22 06:00 MHDA- 2022/03/22 06:00 PMCR- 2022/01/20 CRDT- 2022/01/21 05:44 PHST- 2021/10/31 00:00 [received] PHST- 2021/12/30 00:00 [accepted] PHST- 2022/01/21 05:44 [entrez] PHST- 2022/01/22 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2022/01/20 00:00 [pmc-release] AID - 10.1186/s12951-021-01236-1 [pii] AID - 1236 [pii] AID - 10.1186/s12951-021-01236-1 [doi] PST - epublish SO - J Nanobiotechnology. 2022 Jan 20;20(1):38. doi: 10.1186/s12951-021-01236-1.