Genetic control of wayward pluripotent stem cells and their progeny after transplantation - PubMed (original) (raw)

Genetic control of wayward pluripotent stem cells and their progeny after transplantation

Maija Kiuru et al. Cell Stem Cell. 2009.

Abstract

The proliferative capacity of pluripotent stem cells and their progeny brings a unique aspect to therapeutics, in that once a transplant is initiated the therapist no longer has control of the therapy. In the context of the recent FDA approval of a human ESC trial and report of a neuronal-stem-cell-derived tumor in a human trial, strategies need to be developed to control wayward pluripotent stem cells. Here, we focus on one approach: direct genetic modification of the cells prior to transplantation with genes that can prevent the adverse events and/or eliminate the transplanted cells and their progeny.

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Figures

Figure 1

Figure 1. The Pluripotent Stem Cell Is the Factory to Generate the Progenitor and Differentiated Cells to Be Transplanted for Therapeutic Purposes

The risks of the various cell populations are indicated. The example is of differentiated cardiac muscle, but the paradigm holds for any differentiated cell type.

Figure 2

Figure 2. Genetic Engineering Strategies to Facilitate Control of Potential Wayward Pluripotent Stem Cells and Their Progeny

The vectors (retrovirus, lentivirus, or plasmid) mediate integration of the expression cassette into the pluripotent stem cell or its progeny depending on the application. The expression cassette contains two elements. One promoter (constitutive, pluripotent, or regulated depending on the need) regulates the “control” gene (pluripotent antisense, enzyme prodrug, toxin or apoptotic, or plasma membrane tag). The second promoter regulates a gene used for selection (antibiotic based or a plasma membrane tag). The stem cell population that has been genetically modified is then selected and transferred to the patient as dictated by the therapeutic needs. If there is a need to control a wayward stem cell population, the promoter is activated and/or a prodrug administered, eliminating the wayward cells.

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References

    1. Addis RC, Bulte JW, Gearhart JD. Special cells, special considerations: the challenges of bringing embryonic stem cells from the laboratory to the clinic. Clin Pharmacol Ther. 2008;83:386–389. - PMC - PubMed
    1. Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, Paz N, Koren-Michowitz M, Waldman D, Leider-Trejo L, et al. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med. 2009;6:e1000029. doi: 10.1371/journal.pmed.1000029. - DOI - PMC - PubMed
    1. Amit M, Itskovitz-Eldor J. Derivation and spontaneous differentiation of human embryonic stem cells. J Anat. 2002;200:225–232. - PMC - PubMed
    1. Aractingi S, Kanitakis J, Euvrard S, Le DC, Peguillet I, Khosrotehrani K, Lantz O, Carosella ED. Skin carcinoma arising from donor cells in a kidney transplant recipient. Cancer Res. 2005;65:1755–1760. - PubMed
    1. Arafat WO, Gomez-Navarro J, Xiang J, Barnes MN, Mahasreshti P, Alvarez RD, Siegal GP, Badib AO, Buchsbaum D, Curiel DT, Stackhouse MA. An adenovirus encoding proapoptotic Bax induces apoptosis and enhances the radiation effect in human ovarian cancer. Mol Ther. 2000;1:545–554. - PubMed

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