Dictyostelium discoideum is a promising eukaryotic host for the expression of heterologous proteins requiring post-translational modifications. However, the dilute nature of D. discoideum cell culture limits applications for high value proteins production. D. discoideum cells, entrapped in sodium cellulose sulfate/poly-dimethyl-diallyl-ammonium chloride (NaCS-PDMDAAC) capsules were used for biosynthesis of the heterologous protein, soluble human Fas ligand (hFasL). Semi-continuous cultivations with capsules recycling were carried out in shake flasks. Also, a scaled-up cultivation of immobilized D. discoideum for hFasL production in a customized vitreous airlift bioreactor was conducted. The results show that NaCS-PDMDAAC capsules have desirable biophysical properties including biocompatibility with the D. discoideum cells and good mechanical stability throughout the duration of cultivation. A maximum cell density of 2.02 x 10(7) cells mL(-1) (equivalent to a maximum cell density of 2.22 x 10(8) cells mL(-1) in capsules) and a hFasL concentration of 130.40 g L-1 (equivalent to a hFasL concentration of 1434.40 g L-1 in capsules) were obtained in shake flask cultivation with capsules recycling. Also, a maximum cell density of 1.72 x 10(7)cells mL(-1) (equivalent to a maximum cell density of 1.89 x 10(8) cells mL(-1) in capsules) and a hFasL concentration of 106.10 g L-1 (equivalent to a hFasL concentration of 1167.10 g L-1 in capsules) were obtained after approximate to 170 h cultivation in the airlift bioreactor (with a working volume of 200 mL in a 315 mL bioreactor). As the article presents a premier work in the application of NaCS-PDMDAAC immobilized D. discoideum cells for the production of hFasL, more work is required to further optimize the system to generate higher cell densities and hFasL titers for large-scale applications. (c) 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:424-430, 2015