Small extracellular vesicles from iPSC-derived mesenchymal stem cells ameliorate tendinopathy pain by inhibiting mast cell activation

被引:25
作者
Gao, Renzhi [1 ,2 ]
Ye, Teng [1 ,2 ]
Zhu, Zhaochen [1 ,2 ]
Li, Qing [1 ]
Zhang, Juntao [1 ]
Yuan, Ji [1 ]
Zhao, Bizeng [2 ]
Xie, Zongping [2 ]
Wang, Yang [1 ]
机构
[1] Shanghai Jiao Tong Univ, Inst Microsurg Extrem, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Orthopaed Surg, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China
基金
中国国家自然科学基金;
关键词
iMSC-sEV; mast cell; pain; tendinopathy; HYPERSENSITIVITY; DEGRANULATION; SENSITIZATION; MSC;
D O I
10.2217/nnm-2022-0036
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: This study aimed to explore the effect of small extracellular vesicles from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) on acute pain and investigate the underlying mechanisms. Materials & methods: The pathology of tendons was accessed by hematoxylin and eosin staining, immunohistochemical and immunofluorescent staining. The pain degree was measured by pain-related behaviors. In vitro, we performed beta-hexosaminidase release assay, RT-qPCR, toluidine blue staining, ELISA and RNA sequencing. Results: iMSC-sEVs effectively alleviated acute pain in tendinopathy as well as inhibiting activated mast cell infiltration and interactions with nerve fibers in vivo. In vitro, iMSC-sEVs reduced the degranulation of mast cells and the expression of proinflammatory cytokines and genes involved in the HIF-1 signaling pathway. Conclusion: This study demonstrated that iMSC-sEVs relieved tendinopathy-related pain through inhibiting mast cell activation via the HIF-1 signaling pathway.
引用
收藏
页码:513 / 529
页数:17
相关论文
共 55 条
[41]   Mast Cells and Sensory Nerves Contribute to Neurogenic Inflammation and Pruritus in Chronic Skin Inflammation [J].
Siiskonen, Hanna ;
Harvima, Ilkka .
FRONTIERS IN CELLULAR NEUROSCIENCE, 2019, 13
[42]   Preparation of EGCG decorated, injectable extracellular vesicles for cartilage repair in rat arthritis [J].
Song, Changwei ;
Xu, Shibo ;
Chang, Linna ;
Zhao, Xingjun ;
Mei, Xifan ;
Ren, Xiuli ;
Chen, Zhenhua .
REGENERATIVE BIOMATERIALS, 2021, 8 (06)
[43]   The roles of inflammatory mediators and immunocytes in tendinopathy [J].
Tang, Chenqi ;
Chen, Yangwu ;
Huang, Jiayun ;
Zhao, Kun ;
Chen, Xiao ;
Yin, Zi ;
Heng, Boon Chin ;
Chen, Weishan ;
Shen, Weiliang .
JOURNAL OF ORTHOPAEDIC TRANSLATION, 2018, 14 :23-33
[44]   Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines [J].
Thery, Clotilde ;
Witwer, Kenneth W. ;
Aikawa, Elena ;
Jose Alcaraz, Maria ;
Anderson, Johnathon D. ;
Andriantsitohaina, Ramaroson ;
Antoniou, Anna ;
Arab, Tanina ;
Archer, Fabienne ;
Atkin-Smith, Georgia K. ;
Ayre, D. Craig ;
Bach, Jean-Marie ;
Bachurski, Daniel ;
Baharvand, Hossein ;
Balaj, Leonora ;
Baldacchino, Shawn ;
Bauer, Natalie N. ;
Baxter, Amy A. ;
Bebawy, Mary ;
Beckham, Carla ;
Zavec, Apolonija Bedina ;
Benmoussa, Abderrahim ;
Berardi, Anna C. ;
Bergese, Paolo ;
Bielska, Ewa ;
Blenkiron, Cherie ;
Bobis-Wozowicz, Sylwia ;
Boilard, Eric ;
Boireau, Wilfrid ;
Bongiovanni, Antonella ;
Borras, Francesc E. ;
Bosch, Steffi ;
Boulanger, Chantal M. ;
Breakefield, Xandra ;
Breglio, Andrew M. ;
Brennan, Meadhbh A. ;
Brigstock, David R. ;
Brisson, Alain ;
Broekman, Marike L. D. ;
Bromberg, Jacqueline F. ;
Bryl-Gorecka, Paulina ;
Buch, Shilpa ;
Buck, Amy H. ;
Burger, Dylan ;
Busatto, Sara ;
Buschmann, Dominik ;
Bussolati, Benedetta ;
Buzas, Edit, I ;
Byrd, James Bryan ;
Camussi, Giovanni .
JOURNAL OF EXTRACELLULAR VESICLES, 2018, 7 (01)
[45]   Protein Profiling and Sizing of Extracellular Vesicles from Colorectal Cancer Patients via Flow Cytometry [J].
Tian, Ye ;
Ma, Ling ;
Gong, Manfei ;
Su, Guoqiang ;
Zhu, Shaobin ;
Zhang, Wenqiang ;
Wang, Shuo ;
Li, Zhibin ;
Chen, Chaoxiang ;
Li, Lihong ;
Wu, Lina ;
Yan, Xiaomei .
ACS NANO, 2018, 12 (01) :671-680
[46]   Mammalian MSC from selected species: Features and applications [J].
Uder, Christiane ;
Brueckner, Sandra ;
Winkler, Sandra ;
Tautenhahn, Hans-Michael ;
Christ, Bruno .
CYTOMETRY PART A, 2018, 93A (01) :32-49
[47]   Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities [J].
Varderidou-Minasian, Suzy ;
Lorenowicz, Magdalena J. .
THERANOSTICS, 2020, 10 (13) :5979-5997
[48]   Small extracellular vesicles secreted by human iPSC-derived MSC enhance angiogenesis through inhibiting STAT3-dependent autophagy in ischemic stroke [J].
Xia, Yuguo ;
Ling, Xiaozheng ;
Hu, Guowen ;
Zhu, Qingwei ;
Zhang, Juntao ;
Li, Qing ;
Zhao, Bizeng ;
Wang, Yang ;
Deng, Zhifeng .
STEM CELL RESEARCH & THERAPY, 2020, 11 (01)
[49]   Increased expression of nerve growth factor correlates with visceral hypersensitivity and impaired gut barrier function in diarrhoea-predominant irritable bowel syndrome: a preliminary explorative study [J].
Xu, X. J. ;
Zhang, Y. L. ;
Liu, L. ;
Pan, L. ;
Yao, S. K. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2017, 45 (01) :100-114
[50]   Substance P participates in periodontitis by upregulating HIF-1α and RANKL/OPG ratio [J].
Yan, Kaixian ;
Lin, Qin ;
Tang, Kailiang ;
Liu, Shuang ;
Du, Yi ;
Yu, Xijiao ;
Li, Shu .
BMC ORAL HEALTH, 2020, 20 (01)