Original Article
Cancer Gene Therapy (2007) 14, 828–835; doi:10.1038/sj.cgt.7701077; published online 29 June 2007
Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors
R S Rachakatla1, F Marini2, M L Weiss1, M Tamura1 and D Troyer1
- 1Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA
- 2Department of Blood and Marrow Transplantation, University of Texas MD Anderson Center, Houston, TX, USA
Correspondence: Professor D Troyer, Kansas State University, 1600 Denison Avenue, 228 Coles Hall, Manhattan, KS 66506-5602, USA. E-mail: troyer@vet.ksu.edu
Received 22 March 2007; Revised 28 April 2007; Accepted 26 May 2007; Published online 29 June 2007.
Abstract
Umbilical cord matrix stem (UCMS) cells are unique stem cells derived from Wharton's jelly, which have been shown to express genes characteristic of primitive stem cells. To test the safety of these cells, human UCMS cells were injected both intravenously and subcutaneously in large numbers into severe combined immunodeficiency (SCID) mice and multiple tissues were examined for evidence of tumor formation. UCMS cells did not form gross or histological teratomas up to 50 days posttransplantation. Next, to evaluate whether UCMS cells could selectively engraft in xenotransplanted tumors, MDA 231 cells were intravenously transplanted into SCID mice, followed by intravenous transplantation of UCMS cells 1 and 2 weeks later. UCMS cells were found near or within lung tumors but not in other tissues. Finally, UCMS cells were engineered to express human interferon beta – designated 'UCMS-IFN-
'. UCMS-IFN-
cells were intravenously transplanted at multiple intervals into SCID mice bearing MDA 231 tumors and their effect on tumors was examined. UCMS-IFN-
cells significantly reduced MDA 231 tumor burden in SCID mouse lungs indicated by wet weight. These results clearly indicate safety and usability of UCMS cells in cancer gene therapy. Thus, UCMS cells can potentially be used for targeted delivery of cancer therapeutics.
Keywords:
UCMS cells, MDA 231 human breast cancer cells, adenovirus, interferon beta, lung tumors, stem cell therapy
Abbreviations:
DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethylsulfoxide; EDTA, ethylenediaminetetraacetic acid; ESCs, embryonic stem cells; FBS, fetal bovine serum; HEPA, high-efficiency particulate air; IACUC, institutional animal care and use committees; IBC, institutional biosafety committee; IFN-
, interferon beta; PBS, phosphate-buffered saline; SCID, severe combined immunodeficiency; SP-DiI, sulfonated derivatives of dialkyl indol dye; UCMS cells, umbilical cord matrix stem cells; UCMS-IFN-
cells, interferon-beta-expressing UCMS cells; MDA 231 cells, MD Anderson 231 human breast carcinoma cells
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