Exosomal miR-494 from Bone Marrow Mesenchymal Stem Cells Attenuates Ferroptosis and Enhances Spinal Cord Injury Repair by Modulating the SIRT1/HO-1 Pathway

Zipser CM, Cragg JJ, Guest JD, Fehlings MG, Jutzeler CR, Anderson AJ et al (2022) Cell-based and stem-cell-based treatments for spinal cord injury: evidence from clinical trials. Lancet Neurol 21(7):659–670

Article  PubMed  Google Scholar 

Zhang X, Jiang W, Lu Y, Mao T, Gu Y, Ju D et al (2023) Exosomes combined with biomaterials in the treatment of spinal cord injury. Front Bioeng Biotechnol 11:1077825

Article  PubMed  PubMed Central  Google Scholar 

Zou Z, Liu R, Wang Y, Tan H, An G, Zhang B et al (2023) Protein arginine methyltransferase 8 regulates ferroptosis and macrophage polarization in spinal cord injury via glial cell-derived neurotrophic factor. CNS Neurosci Ther 29(8):2145–2161

Article  CAS  PubMed  PubMed Central  Google Scholar 

(2019) Corrigendum: Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis. Neural Regen Res 14(6):1068

Yan H, Talty R, Aladelokun O, Bosenberg M, Johnson CH (2023) Ferroptosis in colorectal cancer: a future target? Br J Cancer 128(8):1439–1451

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang X, Duan H, Li S, Zhang J, Dong L, Ding J et al (2024) Yap1 alleviates sepsis associated encephalopathy by inhibiting hippocampus ferroptosis via maintaining mitochondrial dynamic homeostasis. J Cell Mol Med 28(19):e70156

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH et al (2019) The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575(7784):688–692

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yao S, Pang M, Wang Y, Wang X, Lin Y, Lv Y et al (2023) Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis. Redox Biol 67:102871

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma C, Wang C, Zhang Y, Li Y, Fu K, Gong L et al (2023) Phillygenin inhibited M1 macrophage polarization and reduced hepatic stellate cell activation by inhibiting macrophage exosomal miR-125b-5p. Biomed Pharmacother 159:114264

Article  CAS  PubMed  Google Scholar 

Xiao M, Zhang J, Chen W, Chen W (2018) M1-like tumor-associated macrophages activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma. J Exp Clin Cancer Res 37(1):143

Article  PubMed  PubMed Central  Google Scholar 

Zhang Y, Zuo B, Yu Z, Zhao K, Zhang Y, He K et al (2023) Complete remission of tumors in mice with neoantigen-painted exosomes and anti-PD-1 therapy. Mol Ther 31(12):3579–3593

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang L, Chen J, Song J, Xiang Y, Yang M, Xia L et al (2024) Activation of the Wnt/β-catenin signalling pathway enhances exosome production by hucMSCs and improves their capability to promote diabetic wound healing. J Nanobiotechnology 22(1):373

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ran N, Gao X, Dong X, Li J, Lin C, Geng M et al (2020) Effects of exosome-mediated delivery of myostatin propeptide on functional recovery of mdx mice. Biomaterials 236:119826

Article  CAS  PubMed  Google Scholar 

Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z et al (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu R, Zhang F, He X, Huang K (2025) Plant derived exosome-like nanoparticles and their therapeutic applications in glucolipid metabolism diseases. J Agric Food Chem

Gu S, Xie R, Liu X, Shou J, Gu W, Che X. RETRACTED: Gu et al (2017) Long coding RNA XIST contributes to neuronal apoptosis through the downregulation of AKT phosphorylation and is negatively regulated by miR-494 in rat spinal cord injury. Int J Mol Sci 18:732. Int J Mol Sci. 2025;26(1).

Yao C, Sun J, Luo W, Chen H, Chen T, Chen C et al (2024) Down-expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenesis and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Bone Joint Res 13(2):52–65

Article  PubMed  PubMed Central  Google Scholar 

Ding YN, Wang HY, Chen XF, Tang X, Chen HZ (2025) Roles of sirtuins in cardiovascular diseases: mechanisms and therapeutics. Circ Res 136(5):524–550

Article  CAS  PubMed  Google Scholar 

Li J, Cui S, Li Y, Zhang C, Chang C, Jian F (2025) Sirtuin1 in spinal cord injury: regulatory mechanisms, microenvironment remodeling and therapeutic potential. CNS Neurosci Ther 31(2):e70244

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nazeam JA, Black I, Mulamoottil VA, Selim NM, El Shiekh RA, Abu-Elfotuh K et al (2025) Okra seed polysaccharides mitigate neuroinflammation and cognitive impairment via modulation of Nrf2/HO-1, HMGB1/RAGE/TLR4/NF-κB, NLRP3/Caspase-1, JAK-2/STAT-3, AMPK/SIRT1/m-TOR, PI3K/AKT/CREB/BDNF/TrkB and PERK/CHOP/Bcl-2 axes. Int Immunopharmacol 148:114110

Article  CAS  PubMed  Google Scholar 

Ju D, Dong C (2024) The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury. Neural Regen Res 19(8):1751–1758

Article  CAS  PubMed  Google Scholar 

Hellenbrand DJ, Quinn CM, Piper ZJ, Elder RT, Mishra RR, Marti TL et al (2024) The secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation. Neural Regen Res 19(6):1308–1317

Article  CAS  PubMed  Google Scholar 

Cui M, Chen F, Shao L, Wei C, Zhang W, Sun W et al (2024) Mesenchymal stem cells and ferroptosis: clinical opportunities and challenges. Heliyon 10(3):e25251

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wawruszak A, Luszczki J, Bartuzi D, Kalafut J, Okon E, Czerwonka A et al (2025) Selisistat, a SIRT1 inhibitor, enhances paclitaxel activity in luminal and triple-negative breast cancer: in silico, in vitro, and in vivo studies. J Enzyme Inhib Med Chem 40(1):2458554

Article  PubMed  PubMed Central  Google Scholar 

Umrath F, Frick SL, Wendt V, Naros A, Zimmerer R, Alexander D (2025) Inhibition of TGF-β signaling enhances osteogenic potential of iPSC-derived MSCs. Sci Rep 15(1):7814

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaka GR, Modarresi F (2025) Conditioned medium derived from mesenchymal stem cells and spinal cord injury: a review of the current therapeutic capacities. IBRO Neurosci Rep 18:293–299

Article  PubMed  PubMed Central  Google Scholar 

Chen P, Li B, Lu Z, Xu Q, Zheng H, Jiang S, et al (2025) PCBP2 as an intrinsic agi ng factor regulates the senescence of hBMSCs through the ROS-FGF2 signaling axis. Elife 13

Huang W, Lin M, Yang C, Wang F, Zhang M, Gao J et al (2021) Rat bone mesenchymal stem cell-derived exosomes loaded with miR-494 promoting neurofilament regeneration and behavioral function recovery after spinal cord injury. Oxid Med Cell Longev 2021:1634917

Article  PubMed  PubMed Central  Google Scholar 

Li Q, Fu X, Kou Y, Han N (2023) Engineering strategies and optimized delivery of exosomes for theranostic application in nerve tissue. Theranostics 13(12):4266–4286

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lai X, Wang Y, Wang X, Liu B, Rong L (2022) miR-146a-5p-modified hUCMSC-derived exosomes facilitate spinal cord function recovery by targeting neurotoxic astrocytes. Stem Cell Res Ther 13(1):487

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou W, Silva M, Feng C, Zhao S, Liu L, Li S et al (2021) Exosomes derived from human placental mesenchymal stem c

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