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

Abstract

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; > or = 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 > or = 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.

Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy

“…HHP between 100-150 MPa induces apoptosis of murine cells, HHP between 150-250 MPa affects the viability of human cells, whereas HHP treatment between 300-400 MPa (dependant of the cell type) leads to cell necrosis. [79][80][81] HHP treatment causes cell rounding, cytoplasmic gelification, the inhibition of enzymatic functions and synthesis of cellular proteins. However, DNA does not seem to be affected by HHP below 1000 MPa.…”

“…However, DNA does not seem to be affected by HHP below 1000 MPa. 81 In biotechnology, HHP is applied to sterilize food, human transplants and pharmaceuticals. 81,82 The use of HHP as a cancer treatment modality was described in 1972 for the treatment of bladder carcinoma.…”

“…81 In biotechnology, HHP is applied to sterilize food, human transplants and pharmaceuticals. 81,82 The use of HHP as a cancer treatment modality was described in 1972 for the treatment of bladder carcinoma. 83 The hydrostatic bladder dilatation method was subsequently tested in cancer patients in a small clinical trial.…”

Células Fetais Bovinas De Cultivo Primário Submetidas a Diferentes Pressões Negativas Antes Do Congelamento Em Palhetas

“…Foi relatado (14) que células submetidas a elevados patamares de pressão hidrostática aumentam progressivamente a rigidez de membranas e a desnaturação de proteínas, o que pode inativar a célula, ou iniciar um processo de morte celular. A excessiva pressão hidrostática determina a morte celular por apoptose ou por necrose, na faixa de 200 Mpa, quando a pressão é superior a 300 Mpa (7) . As menores taxas de sobrevivência observadas com a maior pressão testada (800 mbar) sugerem que a pressão foi excessiva e induziu uma resposta negativa das células.…”

“…Todavia, o uso de pressão hidrostática nos sistemas biológicos é multifacetado. Células eucarióticas submetidas à pressão de até 100 MPa produzem uma resposta reversível similar às proteínas heat shock, sem afetar a viabilidade celular (7) . Já células submetidas a pressões maiores, entre 100 e 200 Mpa, apresentam comportamento distinto, com indução de apoptose.…”