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Cells Under Pressure - Treatment of Eukaryotic Cells with High Hydrostatic Pressure, from Physiologic Aspects to Pressure Induced Cell Death

Journal

CURRENT MEDICINAL CHEMISTRY
Volume 15, Issue 23, Pages 2329-2336

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986708785909166

Keywords

High hydrostatic pressure; stress response; cell death; apoptosis; necrosis; immunogenicity; tumour vaccine; transplants

Funding

  1. The Doktor Robert Pfleger Foundation, Bamberg, Germany
  2. The European Commissions [TPA4 FP6]
  3. The Fund for Research and Teaching at the University Hospital of Friedrich-Alexander-University Erlangen-Nuremberg (ELAN)
  4. The Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg
  5. Deutsche Forschungsgemeinschaft [GK592]
  6. Berdelle-Hilge, Bodenheim, Germany

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The research on high hydrostatic pressure in medicine and life sciences is multifaceted. According to the used pressure head the research has to be divided into two different parts. To study physiological aspects of pressure on eukaryotic cells physiological pressure (pHHP; < 100 MPa) is used. pHHP induces morphological alterations in the cellular organelles and evokes a reversible stress response similar to the well known heat shock response. pHHP induces highly reversible alterations and normally does not affect cellular viability. The treatment of eukaryotic cells with non-physiological pressure (HHP; >= 100 MPa) reveals different outcomes. Treatment with HHP < 150 MPa does not markedly affect viability of human cells, but induces apoptosis in murine cells. In human cells apoptosis is observed after treatment with >= 200 MPa. Moreover, HHP treatment with > 300 MPa leads to necrosis. Therefore, HHP plays a role for the sterilisation of human transplants, of food stuff, and pharmaceuticals. Human tumour cells subjected to HHP > 300 MPa display a necrotic phenotype along with a gelificated cytoplasm, preserve their shape, and retain their immunogenicity. These observations favour the use of HHP to produce whole cell based tumour vaccines. Further experiments revealed that the increment of pressure as well as the pressure holding time influences the cell death of tumour cells. We conclude that high hydrostatic pressure offers both, an economic, easy to apply, clean, and fast technique for the generation of vaccines, and a promising tool to study physiological aspects.

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