Research Article

软骨细胞再生中的干细胞或无细胞基因治疗:滑膜液来源的间充质干细胞外泌体

卷 24, 期 7, 2024

发表于: 19 October, 2023

页: [906 - 919] 页: 14

弟呕挨: 10.2174/0115665240266016231014081916

open access plus

conference banner
摘要

背景:软骨损伤是目前最常见的关节疾病。以往的研究强调使用干细胞作为再生软骨损伤的有效治疗方法。 目的:在本研究中,考虑到细胞治疗方法的困难,假设人类滑膜液来源的间充质干细胞(hSFMSC)外泌体作为SC来源可用于治疗这些损伤,这是一种更安全、无细胞的治疗替代程序,因为它与软骨再生直接相关。此外,本研究旨在确定SC联合基因治疗形成所需的miRNA和靶基因,以揭示软骨再生的机制,提高其有效性。 方法:流式细胞术对MSCs进行表征,并进行免疫细胞化学和分化分析。为了表征功能分离的外泌体,进行了体外摄取分析。利用RT-qPCR检测细胞治疗和无细胞治疗的优势,比较由hSF-MSCs分化而成的成熟人成软骨细胞和人软骨细胞谱,以证明上述hSF-MSCs及其分离的外泌体的谱,以及SC治疗修复软骨损伤的有效性 结果:根据我们的研究结果,hsa-miR-155-5p在人滑膜液MSCs分化的软骨细胞中的表达水平明显高于成熟的人软骨细胞。这些发现也得到了TGF信号通路和软骨形成标记基因的支持。 结论:综上所述,hSF-MSCs和外泌体可用于软骨损伤的治疗,hsa-miR-155-5p可作为一种新的基因治疗方法的靶miRNA,因为它可以提高软骨损伤的治疗效果。

关键词: 软骨缺损,滑膜液间充质干细胞,外泌体,软骨形成,hsa-miR-155-5p,胎儿人成软骨细胞系。

[1]
Zhao W, Wang T, Luo Q, et al. Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling. J Orthop Res 2016; 34(5): 763-70.
[http://dx.doi.org/10.1002/jor.23079] [PMID: 26496668]
[2]
Hosseini S, Taghiyar L, Safari F, Baghaban Eslaminejad M. Regenerative medicine applications of mesenchymal stem cells. Adv Exp Med Biol 2018; 1089: 115-41.
[http://dx.doi.org/10.1007/5584_2018_213] [PMID: 29767289]
[3]
Loo S, Wong N. Advantages and challenges of stem cell therapy for osteoarthritis (Review). Biomed Rep 2021; 15(2): 67.
[http://dx.doi.org/10.3892/br.2021.1443] [PMID: 34155451]
[4]
Chang C, Yan J, Yao Z, Zhang C, Li X, Mao HQ. Effects of mesenchymal stem cell‐derived paracrine signals and their delivery strategies. Adv Healthc Mater 2021; 10(7): 2001689.
[http://dx.doi.org/10.1002/adhm.202001689] [PMID: 33433956]
[5]
Mirotsou M, Jayawardena TM, Schmeckpeper J, Gnecchi M, Dzau VJ. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol 2011; 50(2): 280-9.
[http://dx.doi.org/10.1016/j.yjmcc.2010.08.005] [PMID: 20727900]
[6]
Wei W, Ao Q, Wang X, et al. Mesenchymal stem cell–derived exosomes: A promising biological tool in nanomedicine. Front Pharmacol 2021; 11: 590470.
[http://dx.doi.org/10.3389/fphar.2020.590470] [PMID: 33716723]
[7]
Ferguson SW, Nguyen J. Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity. J Control Release 2016; 228: 179-90.
[http://dx.doi.org/10.1016/j.jconrel.2016.02.037] [PMID: 26941033]
[8]
Nikfarjam S, Rezaie J, Zolbanin NM, Jafari R. Mesenchymal stem cell derived-exosomes: A modern approach in translational medicine. J Transl Med 2020; 18(1): 449.
[http://dx.doi.org/10.1186/s12967-020-02622-3] [PMID: 33246476]
[9]
Lai RC, Yeo RWY, Tan KH, Lim SK. Exosomes for drug delivery-a novel application for the mesenchymal stem cell. Biotechnol Adv 2013; 31(5): 543-51.
[http://dx.doi.org/10.1016/j.biotechadv.2012.08.008] [PMID: 22959595]
[10]
Shang X, Fang Y, Xin W, You H. The application of extracellular vesicles mediated mirnas in osteoarthritis: Current knowledge and perspective. J Inflamm Res 2022; 15: 2583-99.
[http://dx.doi.org/10.2147/JIR.S359887] [PMID: 35479833]
[11]
Baglio SR, Pegtel DM, Baldini N. Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Front Physiol 2012; 3: 359.
[http://dx.doi.org/10.3389/fphys.2012.00359] [PMID: 22973239]
[12]
Biancone L, Bruno S, Deregibus MC, Tetta C, Camussi G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant 2012; 27(8): 3037-42.
[http://dx.doi.org/10.1093/ndt/gfs168] [PMID: 22851627]
[13]
Zacharias E, Milton G, Momen-Heravi F, Hu J, Zhang X, Wu Y. Therapeutic uses of exosomes. J Circ Biomark 2013; 1(1)
[14]
Kolhe R, Hunter M, Liu S, et al. Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis. Sci Rep 2017; 7(1): 2029.
[http://dx.doi.org/10.1038/s41598-017-01905-y] [PMID: 28515465]
[15]
Iaquinta MR, Lanzillotti C, Mazziotta C, et al. The role of microRNAs in the osteogenic and chondrogenic differentiation of mesenchymal stem cells and bone pathologies. Theranostics 2021; 11(13): 6573-91.
[http://dx.doi.org/10.7150/thno.55664] [PMID: 33995677]
[16]
Xu C, Ren G, Cao G, et al. miR-155 regulates immune modulatory properties of mesenchymal stem cells by targeting TAK1-binding protein 2. J Biol Chem 2013; 288(16): 11074-9.
[http://dx.doi.org/10.1074/jbc.M112.414862] [PMID: 23449975]
[17]
Pers YM, Bony C, Duroux-Richard I, et al. miR-155 contributes to the immunoregulatory function of human mesenchymal stem cells. Front Immunol 2021; 12: 624024.
[http://dx.doi.org/10.3389/fimmu.2021.624024] [PMID: 33841404]
[18]
Wang W, Rigueur D, Lyons KM. TGFβ signaling in cartilage development and maintenance. Birth Defects Res C Embryo Today 2014; 102(1): 37-51.
[http://dx.doi.org/10.1002/bdrc.21058] [PMID: 24677722]
[19]
van der Kraan PM, Blaney Davidson EN, Blom A, van den Berg WB. TGF-beta signaling in chondrocyte terminal differentiation and osteoarthritis. Osteoarthritis Cartilage 2009; 17(12): 1539-45.
[http://dx.doi.org/10.1016/j.joca.2009.06.008] [PMID: 19583961]
[20]
Sariboyaci A, Uysal O, Gunes S. Differentiation of human bone marrow-derived mesenchymal stem cells into functional pancreatic beta cells. Med Sci 2021; 10(3): 951-8.
[http://dx.doi.org/10.5455/medscience.2021.07.228]
[21]
Duman BO, Sariboyaci AE, Karaoz E. Bio-engineering of 3-D cell sheets for diabetic rats: Interaction between mesenchymal stem cells and beta cells in functional islet regeneration system. Tissue Cell 2022; 79: 101919.
[http://dx.doi.org/10.1016/j.tice.2022.101919] [PMID: 36137362]
[22]
Demircan PC, Sariboyaci AE, Unal ZS, Gacar G, Subasi C, Karaoz E. Immunoregulatory effects of human dental pulp-derived stem cells on T cells: Comparison of transwell co-culture and mixed lymphocyte reaction systems. Cytotherapy 2011; 13(10): 1205-20.
[http://dx.doi.org/10.3109/14653249.2011.605351] [PMID: 21905956]
[23]
Karaöz E, Doğan BN, Aksoy A, et al. Isolation and in vitro characterisation of dental pulp stem cells from natal teeth. Histochem Cell Biol 2010; 133(1): 95-112.
[http://dx.doi.org/10.1007/s00418-009-0646-5] [PMID: 19816704]
[24]
Sariboyaci A, Demircan P, Gacar G, Unal Z, Erman G, Karaoz E. Immunomodulatory properties of pancreatic islet-derived stem cells co-cultured with T cells: Does it contribute to the pathogenesis of type 1 diabetes? Exp Clin Endocrinol Diabetes 2014; 122(3): 179-89.
[http://dx.doi.org/10.1055/s-0034-1367004] [PMID: 25014767]
[25]
Zhou Y, Xu H, Xu W, et al. Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Ther 2013; 4(2): 34.
[http://dx.doi.org/10.1186/scrt194] [PMID: 23618405]
[26]
Zhang R, Ma J, Han J, Zhang W, Ma J. Mesenchymal stem cell related therapies for cartilage lesions and osteoarthritis. Am J Transl Res 2019; 11(10): 6275-89.
[PMID: 31737182]
[27]
Pan Y, Balazs L, Tigyi G, Yue J. Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality. Biochem Biophys Res Commun 2011; 408(3): 369-74.
[http://dx.doi.org/10.1016/j.bbrc.2011.02.119] [PMID: 21371421]
[28]
Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 2017; 7(1): 180-95.
[http://dx.doi.org/10.7150/thno.17133] [PMID: 28042326]
[29]
Mao G, Zhang Z, Hu S, et al. Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Res Ther 2018; 9(1): 247.
[http://dx.doi.org/10.1186/s13287-018-1004-0] [PMID: 30257711]
[30]
Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015; 523(7559): 177-82.
[http://dx.doi.org/10.1038/nature14581] [PMID: 26106858]
[31]
Xu R, Simpson RJ, Greening DW. A protocol for isolation and proteomic characterization of distinct extracellular vesicle subtypes by sequential centrifugal ultrafiltration Exosomes and Microvesicles. Springer 2017; pp. 91-116.
[32]
Chen J, Chen J, Cheng Y, et al. Mesenchymal stem cell-derived exosomes protect beta cells against hypoxia-induced apoptosis via miR-21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation. Stem Cell Res Ther 2020; 11(1): 97.
[http://dx.doi.org/10.1186/s13287-020-01610-0] [PMID: 32127037]
[33]
Swingler TE, Wheeler G, Carmont V, et al. The expression and function of microRNAs in chondrogenesis and osteoarthritis. Arthritis Rheum 2012; 64(6): 1909-19.
[http://dx.doi.org/10.1002/art.34314] [PMID: 22143896]
[34]
Pers YM, Ruiz M, Noël D, Jorgensen C. Mesenchymal stem cells for the management of inflammation in osteoarthritis: State of the art and perspectives. Osteoarthritis Cartilage 2015; 23(11): 2027-35.
[http://dx.doi.org/10.1016/j.joca.2015.07.004] [PMID: 26521749]
[35]
Alivernini S, Gremese E, McSharry C, et al. MicroRNA-155—at the critical interface of innate and adaptive immunity in arthritis. Front Immunol 2018; 8: 1932.
[http://dx.doi.org/10.3389/fimmu.2017.01932] [PMID: 29354135]
[36]
de Kroon LMG, Narcisi R, van den Akker GGH, et al. SMAD3 and SMAD4 have a more dominant role than SMAD2 in TGFβ-induced chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. Sci Rep 2017; 7(1): 43164.
[http://dx.doi.org/10.1038/srep43164] [PMID: 28127051]
[37]
Green JD, Tollemar V, Dougherty M, et al. Multifaceted signaling regulators of chondrogenesis: Implications in cartilage regeneration and tissue engineering. Genes Dis 2015; 2(4): 307-27.
[http://dx.doi.org/10.1016/j.gendis.2015.09.003] [PMID: 26835506]
[38]
Guidotti S, Minguzzi M, Platano D, et al. Glycogen synthase kinase-3β inhibition links mitochondrial dysfunction, extracellular matrix remodelling and terminal differentiation in chondrocytes. Sci Rep 2017; 7(1): 12059.
[http://dx.doi.org/10.1038/s41598-017-12129-5] [PMID: 28127051]
[39]
Kong W, Yang H, He L, et al. MicroRNA-155 is regulated by the transforming growth factor β/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol 2008; 28(22): 6773-84.
[http://dx.doi.org/10.1128/MCB.00941-08] [PMID: 18794355]
[40]
Wang Z, Yan K, Ge G, et al. Exosomes derived from miR-155-5p–overexpressing synovial mesenchymal stem cells prevent osteoarthritis via enhancing proliferation and migration, attenuating apoptosis, and modulating extracellular matrix secretion in chondrocytes. Cell Biol Toxicol 2021; 37(1): 85-96.
[http://dx.doi.org/10.1007/s10565-020-09559-9] [PMID: 33099657]

© 2024 Bentham Science Publishers | Privacy Policy