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Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

Cancer Gene Therapy volume 14, pages 828–835 (2007)Cite this article

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-β’. UCMS−IFN-β cells were intravenously transplanted at multiple intervals into SCID mice bearing MDA 231 tumors and their effect on tumors was examined. UCMS−IFN-β 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.

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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-β:

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-β cells:

interferon-beta-expressing UCMS cells

MDA 231 cells:

MD Anderson 231 human breast carcinoma cells

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Acknowledgements

We thank Marla Pyle for technical assistance and manuscript proofreading, Matt Martinez and Erin Miller for laboratory assistance in tissue sectioning and in vitro studies. This work represents contributions from the National Cancer Institute (Grant nos. CA-1094551 and CA116199-01 for FCM), grants from the Susan G. Komen Breast Cancer Foundation, NIH NS 34160, Terry C Johnson Cancer Center, Kansas State Legislature and the Kansas Agricultural Experiment Station.

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Authors and Affiliations

  1. Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA

    R S Rachakatla, M L Weiss, M Tamura & D Troyer

  2. Department of Blood and Marrow Transplantation, University of Texas MD Anderson Center, Houston, TX, USA

    F Marini

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  1. R S Rachakatla
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  2. F Marini
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Correspondence to D Troyer.

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Rachakatla, R., Marini, F., Weiss, M. et al. Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors. Cancer Gene Ther 14, 828–835 (2007). https://doi.org/10.1038/sj.cgt.7701077

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  • DOI: https://doi.org/10.1038/sj.cgt.7701077

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