PMID- 37789395 OWN - NLM STAT- MEDLINE DCOM- 20231005 LR - 20231121 IS - 1477-3155 (Electronic) IS - 1477-3155 (Linking) VI - 21 IP - 1 DP - 2023 Oct 3 TI - Cerium oxide nanoparticles-carrying human umbilical cord mesenchymal stem cells counteract oxidative damage and facilitate tendon regeneration. PG - 359 LID - 10.1186/s12951-023-02125-5 [doi] LID - 359 AB - BACKGROUND: Tendon injuries have a high incidence and limited treatment options. Stem cell transplantation is essential for several medical conditions like tendon injuries. However, high local concentrations of reactive oxygen species (ROS) inhibit the activity of transplanted stem cells and hinder tendon repair. Cerium oxide nanoparticles (CeONPs) have emerged as antioxidant agents with reproducible reducibility. RESULTS: In this study, we synthesized polyethylene glycol-packed CeONPs (PEG-CeONPs), which were loaded into the human umbilical cord mesenchymal stem cells (hUCMSCs) to counteract oxidative damage. H(2)O(2) treatment was performed to evaluate the ROS scavenging ability of PEG-CeONPs in hUCMSCs. A rat model of patellar tendon defect was established to assess the effect of PEG-CeONPs-carrying hUCMSCs in vivo. The results showed that PEG-CeONPs exhibited excellent antioxidant activity both inside and outside the hUCMSCs. PEG-CeONPs protect hUCMSCs from senescence and apoptosis under excessive oxidative stress. Transplantation of hUCMSCs loaded with PEG-CeONPs reduced ROS levels in the tendon injury area and facilitated tendon healing. Mechanistically, NFkappaB activator tumor necrosis factor alpha and MAPK activator dehydrocrenatine, reversed the therapeutic effect of PEG-CeONPs in hUCMSCs, indicating that PEG-CeONPs act by inhibiting the NFkappaB and MAPK signaling pathways. CONCLUSIONS: The carriage of the metal antioxidant oxidase PEG-CeONPs maintained the ability of hUCMSCs in the injured area, reduced the ROS levels in the microenvironment, and facilitated tendon regeneration. The data presented herein provide a novel therapeutic strategy for tendon healing and new insights into the use of stem cells for disease treatment. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Ren, Xunshan AU - Ren X AD - Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Zhuang, Huangming AU - Zhuang H AD - Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Zhang, Yuelong AU - Zhang Y AD - Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Zhou, Panghu AU - Zhou P AD - Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China. zhoupanghu@whu.edu.cn. LA - eng GR - 2021BCA147/the Hubei Provincial key research and development program/ GR - JCRCFZ-2022-019/Cross-Innovation Talent Program of Renmin Hospital of Wuhan University/ GR - 2042023kf0224/Fundamental Research Funds for Central Universities of the Central South University/ PT - Journal Article DEP - 20231003 PL - England TA - J Nanobiotechnology JT - Journal of nanobiotechnology JID - 101152208 RN - 619G5K328Y (ceric oxide) RN - 0 (Antioxidants) RN - 0 (Reactive Oxygen Species) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Humans MH - Rats MH - Animals MH - Antioxidants/pharmacology MH - Reactive Oxygen Species MH - Hydrogen Peroxide MH - Oxidative Stress MH - *Mesenchymal Stem Cells MH - Regeneration MH - *Nanoparticles/therapeutic use MH - Tendons MH - *Tendon Injuries/therapy MH - Umbilical Cord PMC - PMC10546722 OTO - NOTNLM OT - Cerium oxide OT - Human umbilical cord mesenchymal stem cell OT - Reactive oxygen species OT - Tendon COIS- The authors declare no competing interests. EDAT- 2023/10/04 00:42 MHDA- 2023/10/05 06:43 PMCR- 2023/10/03 CRDT- 2023/10/03 23:52 PHST- 2023/06/27 00:00 [received] PHST- 2023/09/21 00:00 [accepted] PHST- 2023/10/05 06:43 [medline] PHST- 2023/10/04 00:42 [pubmed] PHST- 2023/10/03 23:52 [entrez] PHST- 2023/10/03 00:00 [pmc-release] AID - 10.1186/s12951-023-02125-5 [pii] AID - 2125 [pii] AID - 10.1186/s12951-023-02125-5 [doi] PST - epublish SO - J Nanobiotechnology. 2023 Oct 3;21(1):359. doi: 10.1186/s12951-023-02125-5.