Engineering the fate and function of human T-Cells via 3D bioprinting.

Abstract

T-cell immunotherapy holds promise for the treatment of cancer, infection, and autoimmune diseases. Nevertheless, T-cell therapy is limited by low cell expansion efficiency<i>ex vivo</i>and functional deficits. Here we describe two 3D bioprinting systems made by different biomaterials that mimic the<i>in vivo</i>formation of natural lymph vessels and lymph nodes which modulate T-cell with distinct fates and functions. We observe that coaxial alginate fibers promote T-cell expansion, less exhausted and enable CD4⁺T-cell differentiation into central memory-like phenotype (Tcm), CD8⁺T-cells differentiation into effector memory subsets (Tem), while alginate-gelatin scaffolds bring T-cells into a relatively resting state. Both of the two bioprinting methods are strikingly different from a standard suspension system. The former bioprinting method yields a new system for T-cell therapy and the latter method can be useful for making an immune-chip to elucidate links between immune response and disease.