Abstract 5154: Human umbilical cord matrix stem cells transfected with the interferon-β gene markedly attenuated the growth of bronchioloalveolar carcinoma xenografts in mice

Abstract

Abstract Mesenchymal stem cells derived from the human umbilical cord matrix (UCMSC) have great potential for therapeutic use in multiple diseases including cancer. UCMSC can be used as carriers for targeted delivery of genes or therapeutics and for local production of biologic agents. The therapeutic strategy using UCMSC as cellular vehicles for targeted gene delivery can avoid the problem of short life or excessive toxicity of a particular gene product in vivo. Interferon-β (IFN-β) has demonstrated a potent anti-tumor effect on many tumor cell lines in vitro. However, in vivo inhibition of tumor cell growth by IFN-β required blood concentrations much higher than the maximally tolerated dose. Therefore, clinical therapy by systemic administration of IFN-β was not possible. The aim of this study was to determine the anti-cancer effect of IFN-β gene transfected-UCMSC (IFN-UCMSC) on bronchioloalveolar carcinoma (BAC) cell lines in vitro and in vivo. The conditioned medium derived from IFN-UCMSC significantly attenuated cell growth of H358 and SW1573 BAC cell lines in vitro compared to the medium derived from non-transfected UCMSC. The percentage of dead cells, as measured by the trypan blue exclusion test, was significantly higher in the cells treated with the medium derived from IFN-UCMSC than UCMSC alone. The co-culture of IFN-UCMSC with cancer cells inhibited cell growth significantly through stimulation of apoptosis. Finally, systemic administration of IFN-UCMSC (0.3 million cells/injection, 5 day interval for four times) markedly attenuated tumor multiplicity and size of orthotopic H358 BAC xenografts in SCID mouse lungs. Histochemical analysis of the tumors indicated tumor-targeted localization of UCMSC and significant reduction of tumor cell proliferation index as measured by Ki-67 staining. These results clearly indicated that IFN-β production by IFN-UCMSC attenuated growth of BAC cells by inducing programmed cell death both in vitro and in vivo. This research clearly demonstrated that IFN-UCMSC are a powerful anti-cancer therapeutic tool as delivery vehicles for IFN-β. This work was supported by the KSU Terry C. Johnson Center for Basic Cancer Research, KSU Provost's Fund, KSU CVM Dean's Fund, NIH P20 RR017686 and a Joan's Legacy Research Grant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5154.