Sweet and sticky: increased cell adhesion through click-mediated functionalization of regenerative liver progenitor cells

The burgeoning field of cell therapies is rapidly expanding, offering the promise to tackle complex and unsolved healthcare problems. One prominent example is represented by CAR T-cells, which have been introduced into the clinic for treating a variety of cancers. Promising cell-based candidates have also been developed to promote tissue regeneration, showing high potencies for the treatment of damaged liver. Nevertheless, in the remit of regenerative medicine, cell-therapy efficacies remain suboptimal as a consequence of the low engraftment of injected cells to the existing surrounding tissue. Herein, we present a facile approach to enhance the adhesion and engraftment of therapeutic hepatic progenitor cells (HPCs) through specific and homogeneous cell surface modification with exogenous polysaccharides, without requiring genetic modification. Coated HPCs exhibited significantly increased markers of adhesion and cell spreading, demonstrating preferential interactions with certain extra-cellular matrix proteins. Moreover, they displayed enhanced binding to endothelial cells and 3D liver microtissues. This translatable methodology shows promise for improving therapeutic cell engraftment, offering a potential alternative to liver transplantation in end-stage liver disease.