The human amniotic fluid mesenchymal stem cells therapy on, SKOV3, ovarian cancer cell line

Abstract

Purpose One of the most common malignancies peculiar to female health with few symptoms, low response to therapy, difficult diagnosis, frequent relapse, and high mortality, is ovarian cancer. Thus, our experiment, using Human amniotic fluid mesenchymal stem cells (hAFMSCs) as a therapeutic tool, aims to find an efficient treatment approach for patients suffering from SKOV3 ovarian cancer. Material & Methods In this study, we obtained 5 ml amniotic fluid from 16–20 week pregnant women who underwent amniocentesis for routine prenatal diagnosis by karyotyping in Al‐Zahra Hospital of Tabriz University of Medical Sciences, Iran. Using trans wells in 24 wells plate, hAFMSCs were isolated from all samples, co‐cultured with SKOV3 ovarian cancer cell line, and characterized via flow cytometry and RT‐PCR. Human skin fibroblast cells (HSFCs) were isolated and used as a negative control. SKOV3 and HSFCs' viability after 5 days was evaluated by MTT assay. Cell cycle and apoptotic genes were analyzed by real‐time PCR. Results We successfully isolated and characterized hAFMSCs through it positivity for CD44 and CD90 specific mesenchymal stem cell markers and negativity for CD31 and CD45. Oct4 and NANOG were evaluated by RT‐PCR as pluripotency markers, and visualized on 2% gel electrophoresis. We established hAFMS cell lines after 5 days of co‐culturing the SKOV3 cells, viability was decreased; however, HSFCs did not show toxicity by MTT assay. The genes indicated upregulation and high expression by a real‐time PCR. Conclusions Our findings showed that hAFMSCs have natural tumor tropism, and can release soluble factors in a cell culture, which cause an efficient anticancer effect. Thus, we can use hAFMSCs for complete anticancer therapy on SKOV3 cell line at cell culture condition and possibly in vivo in the near future.

Human amniotic mesenchymal stem cells to promote/suppress cancer: two sides of the same coin

“…MSCs are strong proliferation inhibitors of immune cells like the natural killer cells (NK cells). The same results have been reported on numerous cancer types such as breast cancer [ 45 ], hepatoma [ 46 ], ovarian cancer [ 23 ], and glioma [ 47 ]. It is reported that MSCs exert their growth inhibitory effect through MSC-secreted prostaglandin E2 (PGE2), IL-6, indoleamine2,3- dioxygenase (IDO), TGF-β1, and NO [ 48 , 49 ].…”

“…Some studies have revealed that hAMSCs/hAFMSCs induced tumor growth and metastasis [ 22 ]. However, reports confirming the anti-cancer effects of these cells are also available in literature [ 23 , 24 ]. The controversial results and poor understanding of mechanisms behind the effect of hAMSCs/hAFMSCs on cancer cells hamper those researchers who are trying to use such cells in clinic [ 25 ].…”

Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses

“…Endometrial MSC show anti-cancer effects on human epithelial ovarian cancer cells in vitro and in vivo through paracrine factors [ 92 ]. Human amniotic fluid MSC (hAFMSC), which can be obtained by amniocentesis in the second trimester or at the end of pregnancy [ 93 ], have natural tumor tropism towards ovarian cancer cells, and by releasing soluble factors have an efficient anticancer effect on them [ 94 ]. More recently, human uterine cervical stem cells (hUCESC) or their secretome have shown a potent antitumor effect on HeLa cells, highly proliferating breast cancer cells and cancer-associated fibroblasts [ 42 ].…”

Application of nanomaterials in three‐dimensional stem cell culture

“…Nanofibrous structured scaffolds has been shown to favorably support bone tissue (osteoblast, osteoclast, and fibroblast) proliferation and differentiation in 3D cell cultures for possible implantation . In a recent report on breast cancer, it was revealed that a 3D nanofiber scaffold exerted significant influence on CD44+/CD24− by limiting their migration and invasion tendencies thus further highlighting the importance of cell‐extracellular matrix interaction in stem cell proliferation, which could be exploited for designing therapeutic interventions with better efficacies …”

“…52,53 In a recent report on breast cancer, it was revealed that a 3D nanofiber scaffold exerted significant influence on CD44+/CD24− by limiting their migration and invasion tendencies thus further highlighting the importance of cell-extracellular matrix interaction in stem cell proliferation, which could be exploited for designing therapeutic interventions with better efficacies. 54,55 7 | CLINICAL APPLICATIONS OF SOME NANOMATERIALS…”