title: Antitumor activity of placenta-derived mesenchymal stem cells producing pigment epithelium-derived factor in a mouse melanoma model.
abstract: Mesenchymal stem cells (MSCs) are a new tool that can be used for the delivery of therapeutic agents to tumor cells. Among the various types of MSCs, placenta-derived MSCs (PDMSCs) have emerged as one of the most attractive vehicles for gene therapy due to their high throughput, lack of ethical concerns, non-invasive procedure for their harvesting and ease of isolation. In this study, we evaluated the antitumor activity of human PDMSCs loaded with recombinant adenoviruses expressing pigment epithelium-derived factor (PEDF). PDMSCs were transduced with adenovirus PEDF and the expression of PEDF was confirmed by western blotting and ELISA. The inhibition of angiogenesis mediated by PEDF-expressing PDMSCs (PDMSC-PEDF) was determined using human umbilical vein endothelial cell (HUVEC) proliferation inhibition assay and migration inhibition assayin vitro. Inin vivoexperiments, C57BL/6 mice bearing B16-F10 melanoma were treated with intratumoral injection of PDMSC-PEDF twice at a 4-day interval. The tumor volume and weight were recorded. The results demonstrated that the administration of PDMSC-PEDF resulted in marked suppression of tumor growth in an established melanoma model, which was associated with a decreased number of microvessels and increased apoptosis of tumor cells compared with the controls. The results suggest that human PDMSCs have potential use as effective delivery vehicles for cancer gene therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.forename: Na
authors.initials: N
authors.lastname: Song
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Chen
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
keywords: anti-angiogenesis; gene therapy; melanoma; mesenchymal stem cells; pigment epithelium-derived factor