{"title":"损伤特异性应激诱导外泌体对体内顺铂肾毒性的治疗作用","authors":"Eser Oz Oyar , Aysegul Aciksari , Burcu Azak Pazarlar , Cansu Bilister Egilmez , Gokhan Duruksu , Selenay Furat Rencber , Melda Yardimoglu Yilmaz , Ahmet Ozturk , Yusufhan Yazir","doi":"10.1016/j.mcp.2022.101861","DOIUrl":null,"url":null,"abstract":"<div><p><span>Cisplatin is one of the metal containing </span>drugs<span><span> for the solid cancer treatments. However, its side-effects limit its application in the cancer treatment<span><span>. Stem cell therapy is a promising treatment for the tissue damage caused by the chemotherapeutic agents, like cisplatin. </span>Exosomes secreted by </span></span>mesenchymal stem cells<span><span><span> (MSCs) could be used for cell-free regenerative treatment, but their potency and reproducibility are questionable. In this study, the microenvironment of the renal tubular epithelial cells was mimicked by coculture of endothelial-, renal proximal tubule epithelial- and fibroblast cells. Cisplatin was applied to this tricell culture model, and the secreted rescue signals were collected and used to induce MSCs. From these stress-induced MSCs, the (stress-induced) exosomes were collected and used for the cell-free therapeutic treatment of cisplatin-treated rats with </span>acute kidney injury<span>. The composition of the stress-induces exosomes was compared with the non-induced exosomes and found that the expression of some critical factors for cell proliferation, repair mechanism and </span></span>oxidative stress<span> was improved. The cisplatin-damaged renal tissue showed substantial recovery after the treatment with stress-induced exosomes compared to the treatment with non-induced exosomes. Although, the non-induced exosomes showed their activity mostly as cytoprotective, the induced exosomes further involved actively in the tissue regeneration, like MSCs.</span></span></span></p><p>It was shown that the exosomes could be reprogrammed to improve their therapeutic effect to be used in cell-free regenerative medicine. Further, cisplatin-induced tissue damage in the kidney might be effectively prevented and used for tissue regeneration by use of induced exosomes generated for a particular damage.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The therapeutical effects of damage-specific stress induced exosomes on the cisplatin nephrotoxicity IN VIVO\",\"authors\":\"Eser Oz Oyar , Aysegul Aciksari , Burcu Azak Pazarlar , Cansu Bilister Egilmez , Gokhan Duruksu , Selenay Furat Rencber , Melda Yardimoglu Yilmaz , Ahmet Ozturk , Yusufhan Yazir\",\"doi\":\"10.1016/j.mcp.2022.101861\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Cisplatin is one of the metal containing </span>drugs<span><span> for the solid cancer treatments. However, its side-effects limit its application in the cancer treatment<span><span>. Stem cell therapy is a promising treatment for the tissue damage caused by the chemotherapeutic agents, like cisplatin. </span>Exosomes secreted by </span></span>mesenchymal stem cells<span><span><span> (MSCs) could be used for cell-free regenerative treatment, but their potency and reproducibility are questionable. In this study, the microenvironment of the renal tubular epithelial cells was mimicked by coculture of endothelial-, renal proximal tubule epithelial- and fibroblast cells. Cisplatin was applied to this tricell culture model, and the secreted rescue signals were collected and used to induce MSCs. From these stress-induced MSCs, the (stress-induced) exosomes were collected and used for the cell-free therapeutic treatment of cisplatin-treated rats with </span>acute kidney injury<span>. The composition of the stress-induces exosomes was compared with the non-induced exosomes and found that the expression of some critical factors for cell proliferation, repair mechanism and </span></span>oxidative stress<span> was improved. The cisplatin-damaged renal tissue showed substantial recovery after the treatment with stress-induced exosomes compared to the treatment with non-induced exosomes. Although, the non-induced exosomes showed their activity mostly as cytoprotective, the induced exosomes further involved actively in the tissue regeneration, like MSCs.</span></span></span></p><p>It was shown that the exosomes could be reprogrammed to improve their therapeutic effect to be used in cell-free regenerative medicine. Further, cisplatin-induced tissue damage in the kidney might be effectively prevented and used for tissue regeneration by use of induced exosomes generated for a particular damage.</p></div>\",\"PeriodicalId\":49799,\"journal\":{\"name\":\"Molecular and Cellular Probes\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Probes\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S089085082200072X\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Probes","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S089085082200072X","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
The therapeutical effects of damage-specific stress induced exosomes on the cisplatin nephrotoxicity IN VIVO
Cisplatin is one of the metal containing drugs for the solid cancer treatments. However, its side-effects limit its application in the cancer treatment. Stem cell therapy is a promising treatment for the tissue damage caused by the chemotherapeutic agents, like cisplatin. Exosomes secreted by mesenchymal stem cells (MSCs) could be used for cell-free regenerative treatment, but their potency and reproducibility are questionable. In this study, the microenvironment of the renal tubular epithelial cells was mimicked by coculture of endothelial-, renal proximal tubule epithelial- and fibroblast cells. Cisplatin was applied to this tricell culture model, and the secreted rescue signals were collected and used to induce MSCs. From these stress-induced MSCs, the (stress-induced) exosomes were collected and used for the cell-free therapeutic treatment of cisplatin-treated rats with acute kidney injury. The composition of the stress-induces exosomes was compared with the non-induced exosomes and found that the expression of some critical factors for cell proliferation, repair mechanism and oxidative stress was improved. The cisplatin-damaged renal tissue showed substantial recovery after the treatment with stress-induced exosomes compared to the treatment with non-induced exosomes. Although, the non-induced exosomes showed their activity mostly as cytoprotective, the induced exosomes further involved actively in the tissue regeneration, like MSCs.
It was shown that the exosomes could be reprogrammed to improve their therapeutic effect to be used in cell-free regenerative medicine. Further, cisplatin-induced tissue damage in the kidney might be effectively prevented and used for tissue regeneration by use of induced exosomes generated for a particular damage.
期刊介绍:
MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.