This study was designed to demonstrate the feasibility of producing erythropoietin (EP) from human kidney cells in culture. At present, the only commercially available source of human erythropoietin is from the urine of aplastic anemics. Humans cells in culture represent an excellent alternative source for human erythropoietin. If erythropoietin can be economically produced from human cells in culture, it could serve as the primary source of this hormone. Cell culture has the inherent advantages of ease of production, cost-effectiveness and quality of product. It also eliminates the problem of unidentified contaminants associated with products derived from human blood or urine. A high quality, inexpensive cell culture-derived EP could satisfy the estimated yearly market of $180 million for treatment of erythropoietin-deficiency anemias.The objective of phase I of this study is to screen candidate human kidney cells for their ability to produce EP under normal and induction conditions. Initially, five kidney cell lines were examined for constitutive EP production and secretion. In addition, the conditioned medium of primary rat mesangial cells was also assayed. The assay monitored the EP-dependent production of colony and cluster forming ability (CFU-e) of mouse bone marrow cells in microclot cultures. Based on these studies, three constitutive producers were tentatively identified. Attempts to induce EP production were performed using various induction agents. It is hoped that a suitable producer line and one or more inducing agents will be identified by the completion of this project.National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases
