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Pulsed electric fields for selection of hematopoietic cells and depletion of tumor cell contaminants

Nature Biotechnology volume 18, pages 882–887 (2000)Cite this article

Abstract

Purging of tumor cells and selection of stem cells are key technologies for enabling stem cell transplantation and stem cell gene therapy. Here we report a strategy for cell selection based on physical properties of the cells. Exposing cells to an external pulsed electric field (PEF) increases the natural potential difference across the cell membrane until a critical threshold is reached and pore formation occurs, resulting in fatal perturbation of cell physiology. Attaining this threshold is a function of the applied field intensity and cell size, with larger cells porated at lower field intensities than smaller cells. Since hematopoietic stem cells are smaller than other hematopoietic cells and tumor cells, we found that exposure of peripheral blood mononuclear cells (PBMCs) to PEFs caused stepwise elimination of monocytes without affecting the function of smaller lymphocyte populations. Mobilized peripheral blood exposed to PEFs was enriched for CD34+/CD38− cells and stem cell function was preserved. Furthermore, PEF treatment was able to selectively purge blood preparations of tumor cells and eradicate transplantable tumor.

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Figure 1: PEF exposure time and intensity alters cell viability.
Figure 2: PEF intensity affects the killing of target cells in a size-dependent manner.
Figure 3: Selective killing of tumor cells in a mixed population of PBMCs.
Figure 4
Figure 5: Growth potential of tumor cells in vitro or in vivo is depleted by increasing PEF intensity.
Figure 6: Primitive hematopoietic cells are preserved during PEF treatment.

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Acknowledgements

The authors thank Dr. Dwight Dustin and Mr. Nick Montanarelli, Ballistic Missile Defense Organization, Department of Defense; The National Technology Transfer Center, Alexandria, VA; Booz-Allen & Hamilton, Arlington, VA; the Richard Saltonstall Charitable Foundation (to D.T.S.), and the National Institutes of Health (DK50234, HL55718 to D.T.S., CA7936401 to S.R.L.). We also thank Ms. Mercedes Dekker and Ms. Ellen Kornell for assistance with manuscript preparation and Dr. Richard Evans for figure preparation.

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Authors and Affiliations

  1. Science Research Laboratory Inc., Somerville, 02143, MA

    Henry M. Eppich & Joseph A. Mangano

  2. AIDS Research Center MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, 02129, MA

    Russell Foxall, Kate Gaynor, David Dombkowski, Nobuyuki Miura, Tao Cheng, Sandra Silva-Arrieta, Richard H. Evans, Frederic I. Preffer & David T. Scadden

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Correspondence to David T. Scadden.

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Eppich, H., Foxall, R., Gaynor, K. et al. Pulsed electric fields for selection of hematopoietic cells and depletion of tumor cell contaminants. Nat Biotechnol 18, 882–887 (2000). https://doi.org/10.1038/78504

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