The erythropoietin and regenerative medicine: a lesson from fish

Abstract

Erythropoietin (EPO), the main haematopoietic growth factor for the proliferation and differentiation of erythroid progenitor cells, is also known for its angiogenic and regenerative properties. In this study, we aimed to test the regenerative effects of EPO administration in an experimental model of Sea bass (Dicentrarchus labrax) subjected to amputation of the caudal fin. Erythropoietin-treated fishes (3000 UI of human recombinant EPO-alpha immediately after cutting and after 15 days) showed an increased growth rate of their fins compared with those untreated (anova variance: P: 0.01 vs. P: 0.04). By analysing fin length at established times (15 and 30 days after cut), EPO-treated fishes always showed an increased length compared with untreated ones (T-15: 1.1 +/- 0.2 vs. 0.7 +/- 0.2 cm, P: 0.03; T-30: 1.9 +/- 0.3 vs. 1.2 +/- 0.2 cm, P: 0.01). Moreover, exogenous EPO administration induced an enormous increase in EPO-blood levels at each observation time (T-15: 2240 +/- 210 vs. 16.7 +/- 1.8 mU mL(-1), P < 0.001; T-30: 2340 +/- 190 vs. 17.1 +/- 1.9 mU mL(-1), P < 0.001), whereas these levels remained quite unmodified in untreated fishes. Immunochemical analyses performed by confocal laser scanning microscopic observations showed an increased expression of EPO-receptors and PECAM-1 (an endothelial surface marker of vessels sprout) in the regenerating tissue, whereas no signs of inflammation or fibrosis were recognisable. All these findings confirm EPO as a new factor involved in regenerative processes, also suggesting a potential, future utility for new therapeutical applications in the field of human regenerative medicine.