Creating a Biomimetic Microenvironment for the Ex Vivo Expansion of Primary Human T Lymphocytes

The ex vivo expansion of primary human T cells is of considerable interest. Current protocols call for the addition of massive amounts of stimuli. This study presents as alternative the expansion of such cells in semipermeable sodium cellulose sulfate/poly(diallyldimethyl) ammonium chloride (SCS/PDADMAC) polyelectrolyte microcapsules, which supports at least six cell divisions and results in >40 × 10⁶ cells mL_capsule^-1 within less than 10 d. Inside the microcapsules, the T cells are suspended in a viscous SCS-solution. The low molecular weight cut off (<10 000 Da) of the surrounding polyelectrolyte membrane assures that typical signaling molecules produced by the cells are retained, while nutrients and metabolites can pass. Expensive additives, such as interleukin-2 (IL-2), can be coencapsulated. Expansion then no longer requires specialized T-cell media. Moreover, these results suggest that an SCS with a low degree of sulfation has biomimetic properties, representing an artificial extracellular matrix mimicking heparin sulfate.