Hendijani F, Javanmard Sh Haghjooy, Rafiee L, Sadeghi-Aliabadi H
Department of pharmaceutical biotechnology and Isfahan Pharmaceutical Sciences Research Centre, School of pharmacy and pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2015 Mar-Apr;10(2):134-42.
Multipotent mesenchymal stem cells (MSCs) are recently found to alter the tumor condition. However their exact role in tumor development is not yet fully unraveled. MSCs were established to perform many of their actions through paracrine effect. Thus investigation of MSC secretome interaction with tumor cells may provide important information for scientists who are attempting to apply stem cells in the treatment of the disease. In this study we investigated the effect of human Wharton's jelly derived MSC (WJ-MSCs) secretome on proliferation, apoptotic potential of A549 lung cancer cells, and their response to the chemotherapeutic agent doxorubicin. WJ-MSCs were isolated from human umbilical cord and then characterized according to the International Society for Cellular Therapy criteria and WJ-MSC secretome was collected. BrdU cell proliferation assay and Annexin V-PI staining were used for the evaluation of cytotoxic and proapoptotic effects of WJ-MSC secretome on A549 cells. WJ-MSC secretome neither induced proliferation of lung cancer cells nor affected the apoptotic potential of the tumor cells. We also studied the combinatorial effect of WJ-MSC secretome and the anticancer drug doxorubicinwhich showed no induction of drug resistance when A549 cells was treated with combination of WJ-MSC secretome and doxorubicin. Although MSCs did not show antitumor properties, our in vitro results showed that MSC secretome was not tumorigenic and also did not make lung cancer cells resistant to doxorubicin. Thus MSC secretome could be considered safe for other medical purposes such as cardiovascular, neurodegenerative, and autoimmune diseases which may exist or occur in cancer patients.
多能间充质干细胞(MSCs)最近被发现可改变肿瘤状态。然而,它们在肿瘤发展中的确切作用尚未完全阐明。已证实MSCs通过旁分泌效应发挥多种作用。因此,研究MSCs分泌组与肿瘤细胞的相互作用可能为试图将干细胞应用于该疾病治疗的科学家提供重要信息。在本研究中,我们研究了人脐带华通氏胶来源的MSCs(WJ-MSCs)分泌组对A549肺癌细胞增殖、凋亡潜能以及它们对化疗药物阿霉素反应的影响。从人脐带中分离出WJ-MSCs,然后根据国际细胞治疗协会标准进行鉴定,并收集WJ-MSC分泌组。采用BrdU细胞增殖试验和膜联蛋白V-碘化丙啶染色来评估WJ-MSC分泌组对A549细胞的细胞毒性和促凋亡作用。WJ-MSC分泌组既未诱导肺癌细胞增殖,也未影响肿瘤细胞的凋亡潜能。我们还研究了WJ-MSC分泌组与抗癌药物阿霉素的联合作用,当A549细胞用WJ-MSC分泌组和阿霉素联合处理时,未显示出耐药性诱导。尽管MSCs未表现出抗肿瘤特性,但我们的体外结果表明,MSC分泌组不具有致瘤性,也不会使肺癌细胞对阿霉素产生耐药性。因此,MSC分泌组对于癌症患者可能存在或发生的其他医学目的,如心血管、神经退行性和自身免疫性疾病,可被认为是安全的。