Prospects for insulin delivery by ex-vivo somatic cell gene therapy

The principle of insulin delivery by ex-vivo somatic cell gene therapy invo lves the removal of non-B-cell somatic cells (e.g. fibroblasts) from a diab etic patient, and genetically altering them in vitro to produce and secrete insulin. The cells can be grown in culture and returned to the donor as a source of insulin replacement. Cells modified in this way could be evaluate d before implantation, and reserve stocks could be cryopreserved. By using the patient's own cells, the procedure should obviate the need for immunosu ppression and overcome the problem of tissue supply, while avoiding a recur rence of cell destruction. Ex-vivo somatic cell gene therapy requires an ac cessible and robust cell type that is amenable to multiple transfections an d subject to controlled proliferation. Special problems associated with the use of non-B-cell somatic cells include the processing of proinsulin to in sulin, and the conferment of sensitivity to glucose-stimulated proinsulin b iosynthesis and regulated insulin release. Preliminary studies using fibrob lasts, pituitary cells, kidney (COS) cells and ovarian (CHO) cells suggest that these challenges could be met, and that ex-vivo somatic cell gene ther apy offers a feasible approach to insulin replacement therapy.