Cell Electroporation in Bone Tissue

Electroporation in the cell membrane occurs following exposure to a high-intensity electric field. Electroporation can be used to introduce large molecules into the cell or to induce cell apoptosis by the application of the electric field alone, provided that the cell damage is such that it cannot be recovered. Electroporation use in clinical practice is standardized in association with drugs, electrochemotherapy, for the treatment of cutaneous and subcutaneous tumor nodules. Effective tumor ablation requires complete membrane electroporation of all malignant cells to allow drug diffusion into the cytoplasm. We investigated the impact of the presence of bone trabeculae on electric field effect and whether the mineralized component of the bone prevented the use of electroporation to eradicate tumor cells in bone tissue. We evaluated the possibility of efficiently performing electroporation of osteoblasts and osteocytes, as well as of cells interspersed among bone trabeculae. On healthy rabbits, the effect of electroporation on the distal femoral epiphysis, an area of high osteogenetic activity, was investigated by histological and functional analysis. In bone tissue, complete cell ablation by electroporation was achieved when the absorbed energy dose in the tissue exceeded 3,500 J/Kg. This threshold value was reached with all electric fields tested by increasing the number of pulses delivered. The results of the preclinical investigation set the rationale for the use of electrochemotherapy in patients with bone metastases. Preliminary experience with the use of electrochemotherapy for bone metastases in patients will be discussed.