Cell microencapsulation represents a promising tool for the treatment of many central nervous system (CNS) diseases such as Parkinson's disease. In this technology, cells are surrounded by a semipermeable membrane which protects them from mechanical stress and isolates them from host's immune response. However, if the future clinical application of this strategy is wanted, many challenges remain including the improvement of the mechanical resistance of the microcapsules and the optimization of the intracapsular microenvironment conditions. In this way, the selection of the matrix is essential because the morphological and the physiological behavior of the cells depend on the interactions between the matrix and the enclosed cells. Assuming these considerations, three types of microcapsules elaborated with four different polymers: alginate, cellulose sulfate, agarose and pectin have been fabricated and compared in order to evaluate some key properties such as morphology, size and mechanical stability. Furthermore, GDNF secreting Fischer rat 3T3 fibroblasts were immobilized in each type of capsule and the viability and neurotrophic factor release was determinated. Results showed that the alginate and pectin microcapsules were the most resistant devices, maintaining an adequate microenvironment for the enclosed cells. In contrast, cells entrapped in alginate-cellulose sulfate matrices presented the lowest mechanical resistance, cell viability and GDNF production.