Cytotherapy with naive rat umbilical cord matrix stem cells significantly attenuates growth of murine pancreatic cancer cells and increases survival in syngeneic mice

• Published in: Cytotherapy (Oxford, England) Vol. 12; no. 3; pp. 408 - 417
• Main Authors: Doi, Chiyo, Maurya, Dharmendra Kumar, Pyle, Marla M, Troyer, Deryl, Tamura, Masaaki
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 2010; Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
• Subjects: Advanced Basic Science; Animals; Cell Cycle - physiology; Cell Proliferation; Cell- and Tissue-Based Therapy - methods; Cells, Cultured; Coculture Techniques; colony assay; cytotherapy; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Other; PAN02 cells; pancreatic cancer; Pancreatic Neoplasms - pathology; rat umbilical cord matrix stem cells; Rats; Stem Cells - cytology; Stem Cells - physiology; Survival Rate; Transplantation, Isogeneic; Umbilical Cord - cytology; Xenograft Model Antitumor Assays; xenografts; pancreatic cancer; cytotherapy; rat umbilical cord matrix stem cells; xenografts; colony assay; PAN02 cells
• ISSN: 1465-3249; 1477-2566
• DOI: 10.3109/14653240903548194

Abstract Background aims Pancreatic cancer, sometimes called a ‘silent killer’, 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 USA. Methods A mouse peritoneal model was used to test the ability of unengineered rat umbilical cord matrix-derived stem cells (UCMSC) to control growth of pancreatic cancer. In vivo results were supported by various in vitro assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), direct cell count, [3 H]thymidine uptake and soft agar colony assays. Results 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 tumor cells, as monitored by MTT assay, direct cell counts and [3 H]thymidine uptake assay. Rat UCMSC 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. Histologic study revealed that intraperitoneally administered rat UCMSC survived for at least 3 weeks, and the majority were found near or inside the tumor. Conclusions These results indicate that naive rat UCMSC alone remarkably attenuate the growth of pancreatic carcinoma cells in vitro and in a mouse peritoneal model. This implies that UCMSC could be a potential tool for targeted cytotherapy for pancreatic cancer.