Extracellular vesicles from adipose-derived mesenchymal stem cells promote colony formation ability and EMT of corneal limbal epithelial cells

被引:0
作者
Li, Xiaoqin [1 ]
Hayashi, Ryuhei [1 ,2 ,3 ]
Imaizumi, Tsutomu [2 ,4 ]
Harrington, Jodie [2 ,5 ]
Kudo, Yuji [2 ,4 ]
Takayanagi, Hiroshi [1 ,6 ]
Baba, Koichi [1 ,7 ,8 ]
Nishida, Kohji [1 ,3 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Ophthalmol, Suita, Osaka, Japan
[2] Osaka Univ, Grad Sch Med, Dept Stem Cells & Appl Med, Suita, Osaka, Japan
[3] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Suita, Osaka, Japan
[4] ROHTO Pharmaceut, Basic Res Dev Div, Ikuno ku, Osaka, Japan
[5] Anglia Ruskin Univ, Med Technol Res Ctr, Fac Hlth Educ Med & Social Care, Chelmsford Campus, Chelmsford, England
[6] RAYMEI Inc, Res Dev & Prod Dept, Suita, Osaka, Japan
[7] Osaka Univ, Grad Sch Med, Dept Adv Device Regenerat Med, Suita, Osaka, Japan
[8] Osaka Univ, Grad Sch Med, Visual Regenerat Med, Div Hlth Sci, Suita, Osaka, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
MIGRATION; INVASION; P38; PROLIFERATION; METASTASIS; TRANSITION; EXPRESSION; EXOSOMES; CADHERIN; KINASE;
D O I
10.1371/journal.pone.0321579
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Corneal diseases are a leading cause of visual impairment, and their treatment remains challenging. Corneal epithelial stem cells exist in the limbus, the peripheral region of the cornea, and play an important role in corneal regeneration. Here, we evaluated the effects of extracellular vesicles from human adipose-derived mesenchymal stem cells (AdMSC-EVs) on limbal epithelial cells (LECs). Colony formation assays showed that the colony-forming efficiency of LECs significantly increased in the presence of AdMSC-EVs. We next demonstrated that AdMSC-EVs accelerated the migration of LECs in a scratch assay, whereas the proliferation of LECs was decreased by AdMSC-EVs in the cell proliferation assay. RNA sequencing analysis of LECs indicated that AdMSC-EVs maintained their stem cell properties and improved epithelial-mesenchymal transition (EMT). Furthermore, after identifying the six most abundant microRNAs (miRNAs) in AdMSC-EVs, LEC transfection with miRNA mimics indicated that miR-25, miR-191, and miR-335 were the most probable miRNA factors within AdMSC-EVs at improving colony formation ability and EMT. Taken together, our findings indicated that AdMSC-EVs enhanced the colony formation ability and EMT of LECs, and the effects of AdMSC-EVs were in-part mediated by the miRNAs within the AdMSC-EVs.
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页数:21
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