Targeted use of umbilical cord matrix stem cells for cancer therapy

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dc.contributor.author Rachakatla, Rajashekar
dc.date.accessioned 2008-01-11T21:07:00Z
dc.date.available 2008-01-11T21:07:00Z
dc.date.issued 2008-01-11T21:07:00Z
dc.date.submitted May 2008 en
dc.identifier.uri http://hdl.handle.net/2097/547
dc.description.abstract Umbilical cord matrix stem (UCMS) cells are derived from Wharton's jelly and have been shown to express genes characteristic of primitive stem cells. They can be isolated in large numbers in a short time and thus potentially represent an abundant source of cells for therapeutic use. We investigated the migratory nature of human UCMS cells towards MDA 231 human breast carcinoma cells in an in vitro model of cell migration; UCMS cells cultured with or without MDA 231 cells for 24 hours. Next, we evaluated the effect of chemokines, stromal derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) on human UCMS cells by treating with increasing doses of SDF-1 and VEGF. UCMS cells were found to migrate towards MDA 231 cells in a dose dependent manner. Both SDF-1 and VEGF induced migration of UCMS cells in a dose dependent manner. These results suggest that MDA 231 cells might be releasing chemokine factors, such as SDF-1 and VEGF, which promote UCMS cell migration towards the tumor cells in vitro. Stem cells that migrate to tumors may allow targeted delivery of therapeutic agents that otherwise may have severe side effects. To evaluate the selective engraftment and therapeutic efficiency of human UCMS cells that were engineered to express interferon beta (UCMS-IFN-beta) MDA 231 cells (2,000,000) were intravenously injected into severe combined immune deficient (SCID) mice, followed by three weekly intravenous injections of fluorescently labeled UCMS-IFN-beta cells (500,000). To evaluate the synergistic effect of 5-Fluorouracil (5-FU) and IFN-beta, MDA 231 cells were intravenously injected into SCID mice, followed by three weekly intravenous injections of fluorescently labeled UCMS-IFN-beta cells and three weekly intra peritoneal injections of 5-FU. In both of the above experiments, mice were euthanized one week after the last UCMS cell transplant and lung weights were compared to the controls to determine the differences in tumor burden. After transplantation of UCMS-IFN-beta cells into MDA 231 tumor-bearing mice, UCMS cells were found near or within metastatic lung tumors but not in other tissues, and in these animals, the lung weight was significantly less than MDA 231 tumor-bearing animals that received saline injections. Histologically, there was significant reduction in the tumor area in MDA 231 tumor bearing lungs after UCMS-IFN-beta treatment. When 5-FU was given along with UCMS-IFN-beta cells, there was further reduction in tumor area. These results indicate that UCMS cells can potentially be used for targeted delivery of cancer therapeutics. en
dc.description.sponsorship Kansas Agricultural Experiment Station NIH NS 34160; Terry C. Johnson Cancer Center; Kansas State Legislature en
dc.language.iso en_US en
dc.publisher Kansas State University en
dc.subject Stem cells en
dc.subject Tumors en
dc.subject Interferon beta en
dc.subject 5-FU en
dc.title Targeted use of umbilical cord matrix stem cells for cancer therapy en
dc.type Dissertation en
dc.description.degree Doctor of Philosophy en
dc.description.level Doctoral en
dc.description.department Department of Anatomy and Physiology en
dc.description.advisor Deryl L. Troyer en
dc.subject.umi Biology, Animal Physiology (0433) en
dc.date.published 2008 en
dc.date.graduationmonth May en

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