Abstract 3328: Cytotherapy with naïve rat umbilical cord matrix stem cells significantly attenuates growth of murine pancreatic cancer cells and increases mouse survival in syngeneic mice

Abstract

Abstract Pancreatic cancer is one of the most aggressive human malignancies, with a very poor prognosis. It is the fourth leading cause of cancer-related morbidity and mortality in the United States. MSC derived from the human umbilical cord matrix (UCMSC) have a great potential for therapeutic use in cancer. UCMSC-based targeted gene/therapeutic-delivery and successful tumor attenuation has been demonstrated. However, the targeted stem cell therapy would be significantly safer and more applicable to human patients if unmodified postnatal stem cells alone were shown to cause tumor cell death and regress tumors, without any foreign gene transfection. Accordingly, the aim of this study was to determine the anti-cancer effect of un-engineered naïve rat UCMSC on the growth of murine pancreatic ductal carcinoma in vitro and in vivo. A mouse peritoneal model was used to test the ability of un-engineered rat UCMSC to control growth of pancreatic cancer. In addition, MTT, direct cell count, [3H] thymidine uptake, and soft agar colony assays were carried out as in vitro studies. Co-culture of rat UCMSC with PAN02 murine pancreatic carcinoma cells (UCMSC:PAN02, 1:6 and 1:3) caused G0/G1 arrest and significantly attenuated the proliferation of PAN02 carcinoma cells as monitored by MTT assay, direct cell counts, and [3H] thymidine uptake assay. Rat UCMSCs also significantly reduced PAN02 colony size and number as measured by soft agar colony assay. The in vivo mouse studies showed that rat UCMSC treatment significantly decreased the peritoneal PAN02 tumor burden 3 weeks after tumor transplantation and increased mouse survival time. Histological study revealed that intraperitoneally administered rat UCMSC survived for at least 3 weeks and the majority were found near or inside the tumor. These results indicate that naïve rat UCMSC alone remarkably attenuate the growth of pancreatic carcinoma cells in vitro and in a mouse peritoneal model. Thus, these studies imply that UCMSC could be a potential tool for targeted cytotherapy for pancreatic cancer. This work was supported by Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, KSU College of Veterinary Medicine Dean's fund, Kansas State Legislative Appropriation, NIH P20RR017686, P20RR015563 and R21 CA135599. 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 3328.