PMID- 34938076 OWN - NLM STAT- MEDLINE DCOM- 20211224 LR - 20220429 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 16 DP - 2021 TI - Comparison of Curative Effect of Human Umbilical Cord-Derived Mesenchymal Stem Cells and Their Small Extracellular Vesicles in Treating Osteoarthritis. PG - 8185-8202 LID - 10.2147/IJN.S336062 [doi] AB - INTRODUCTION: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and their small extracellular vesicles (hUC-MSC-sEVs) have shown attractive prospects applying in regenerative medicine. This study aimed to compare the therapeutic effects of two agents on osteoarthritis (OA) and investigate underlying mechanism using proteomics. METHODS: In vitro, the proliferation and migration abilities of chondrocytes treated with hUC-MSCs or hUC-MSC-sEVs were detected by Cell Counting Kit-8 assay and scratch wound assay. In vivo, hUC-MSCs (a single dose of 5 x 10(5)) or hUC-MSC-sEVs (30 mug/time) were injected into the knee joints of anterior cruciate ligament transection-induced OA model. Hematoxylin and eosin, Safranin O/Fast Green staining were used to observe cartilage degeneration. The levels of cartilage matrix metabolic molecules (Collagen II, MMP13 and ADAMTS5) and macrophage polarization markers (CD14, IL-1beta, IL-10 and CD206) were assessed by immunohistochemistry. Finally, proteomics analysis was performed to characterize the proteinaceous contents of two agents. RESULTS: In vitro data showed that hUC-MSC-sEVs were taken up by chondrocytes. A total of 15 mug/mL of sEVs show the greatest proliferative and migratory capacities among all groups. In the animal study, hUC-MSCs and hUC-MSC-sEVs alleviated cartilage damage. This effect was mediated via maintaining cartilage homeostasis, as was confirmed by upregulation of the COL II and downregulation of the MMP13 and ADAMTS5. Moreover, the M1 macrophage markers (CD14) were significantly reduced, while the M2 macrophage markers (CD206 and IL-10) were increased in the hUC-MSCs and hUC-MSC-sEVs relative to the untreated group. Mechanistically, we found that many proteins connected to cartilage repair were more abundant in sEVs. Notably, compared to hUC-MSCs, the upregulated proteins in sEVs were mostly involved in the regulation of immune effector process, extracellular matrix organization, PI3K-AKT signaling pathways, and Rap1 signaling pathway. CONCLUSION: Our study indicated that hUC-MSC-sEVs protect cartilage from damage and many cartilage repair-related proteins are probably involved in the restoration process. These data suggest the promising potential of hUC-MSC-sEVs as a therapeutic agent for OA. CI - (c) 2021 Tang et al. FAU - Tang, Shijie AU - Tang S AUID- ORCID: 0000-0002-7943-2142 AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Chen, Penghong AU - Chen P AUID- ORCID: 0000-0003-2528-1008 AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Zhang, Haoruo AU - Zhang H AUID- ORCID: 0000-0002-7176-4986 AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Weng, Haiyan AU - Weng H AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Fang, Zhuoqun AU - Fang Z AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Chen, Caixiang AU - Chen C AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Peng, Guohao AU - Peng G AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Gao, Hangqi AU - Gao H AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Hu, Kailun AU - Hu K AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Oncology Institution, Fujian Medical University, Fuzhou, 350004, People's Republic of China. FAU - Chen, Jinghua AU - Chen J AD - Department of Pharmaceutical Analysis, the School of Pharmacy, Fujian Medical University, Fuzhou, 350100, People's Republic of China. FAU - Chen, Liangwan AU - Chen L AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. AD - Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. FAU - Chen, Xiaosong AU - Chen X AUID- ORCID: 0000-0002-3780-5510 AD - Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People's Republic of China. AD - Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People's Republic of China. AD - Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People's Republic of China. LA - eng PT - Journal Article DEP - 20211216 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 SB - IM MH - Animals MH - *Extracellular Vesicles MH - Humans MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - *Osteoarthritis/therapy MH - Phosphatidylinositol 3-Kinases MH - Umbilical Cord PMC - PMC8687685 OTO - NOTNLM OT - cell-free therapy OT - human umbilical cord-derived mesenchymal stem cells OT - osteoarthritis OT - proteomics OT - small extracellular vesicles COIS- The authors declare that they have no conflicts of interest for this work. EDAT- 2021/12/24 06:00 MHDA- 2021/12/25 06:00 PMCR- 2021/12/16 CRDT- 2021/12/23 05:45 PHST- 2021/09/01 00:00 [received] PHST- 2021/11/04 00:00 [accepted] PHST- 2021/12/23 05:45 [entrez] PHST- 2021/12/24 06:00 [pubmed] PHST- 2021/12/25 06:00 [medline] PHST- 2021/12/16 00:00 [pmc-release] AID - 336062 [pii] AID - 10.2147/IJN.S336062 [doi] PST - epublish SO - Int J Nanomedicine. 2021 Dec 16;16:8185-8202. doi: 10.2147/IJN.S336062. eCollection 2021.