The in vitro and in vivo characterization of cell-loaded immobilization devices is an important challenge in cell encapsulation technology for the long-term efficacy of this approach. In the present paper, alginate - poly-L-lysine-alginate (APA) microcapsules containing erythropoietin (Epo)-secreting C2C12 myoblasts have been elaborated, characterized, and tested both in vitro and in vivo. High mechanical and chemical resistance of the elaborated microcapsules was observed. Moreover, the in vitro Cultured encapsulated cells released 81.9 +/- 8.2 mIU/mL/24 h (by 100 cell-loaded microcapsules) by day 7, reaching the highest peak at day 21 (161.7 +/- 0.9 mIU/mL/24 h). High and constant hematocrit levels were maintained over 120 days after a single subcutaneous administration of microcapsules and lacking immunosuppressive protocols. No major host reaction was observed. On the basis of the results obtained in our study, cell encapsulation technology might be considered a suitable therapeutic strategy for the long-term delivery of biologically active products, such as Epo.