title: Human umbilical blood mononuclear cell-derived mesenchymal stem cells serve as interleukin-21 gene delivery vehicles for epithelial ovarian cancer therapy in nude mice.
abstract: Ovarian cancer causes more deaths than any other cancer of the female reproductive system, and its overall cure rate remains low. The present study investigated human umbilical blood mononuclear cell (UBMC)-derived mesenchymal stem cells (UBMC-MSCs) as interleukin-21 (IL-21) gene delivery vehicles for ovarian cancer therapy in nude mice. MSCs were isolated from UBMCs and the expanded cells were phenotyped by flow cytometry. Cultured UBMCs were differentiated into osteocytes and adipocytes using appropriate media and then the UBMC-MSCs were transfected with recombinant pIRES2-IL-21-enhancement green fluorescent protein. UBMC-MSCs expressing IL-21 were named as UBMC-MSC-IL-21. Mice with A2780 ovarian cancer were treated with UBMC-MSC-IL-21 intravenously, and the therapeutic efficacy was evaluated by the tumor volume and mouse survival. To address the mechanism of UBMC-MSC-IL-21 against ovarian cancer, the expression of IL-21, natural killer glucoprotein 2 domain and major histocompatibility complex class I chain-related molecules A/B were detected in UBMC-MSC-IL-21 and in the tumor sites. Interferon-γ-secreting splenocyte numbers and natural killer cytotoxicity were significantly increased in the UBMC-MSC-IL-21-treated mice as compared with the UBMC-MSCs or the UBMC-MSC-mock plasmid-treated mice. Most notably, tumor growth was delayed and survival was prolonged in ovarian-cancer-bearing mice treated with UBMC-MSC-IL-21. Our data provide important evidence that UBMC-MSCs can serve as vehicles for IL-21 gene delivery and inhibit the established tumor.
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Zhongda Hospital, Southeast University, Nanjing, People's Republic of China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: He
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.forename: Fangliu
authors.initials: F
authors.lastname: Yu
authors.forename: Longwei
authors.initials: L
authors.lastname: Jiang
authors.forename: Dengyu
authors.initials: D
authors.lastname: Chen
authors.forename: Junsong
authors.initials: J
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000008:administration & dosage / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000628:therapy*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013270:Stomach / Q000473:pathology; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D007371:Interferon-gamma; D000098546:Interleukin-21