The effect of the surface coating of human adipose-derived stem cells by various GAGs on the biodistribution of them upon intravenous administration

Glycosaminoglycans (GAGs) are essential for cell-cell and cell-ECM interactions. Unique structures of GAGs provide high affinities to specific cell receptors. Especially, hyaluronic acid (HA), chondroitin sulfate (CS), and heparin are known to have affinities to the liver sinusoidal endothelial cells (LSECs), so they have been utilized as a ligand for liver targeting nanoparticle systems. In this study, we compared different GAGs as a targeted cell delivery ligand by using lipid-conjugated GAGs. Conjugated lipids of GAGs could provide a stable coating over 2 days on the surface of human adipose-derived stem cells (hADSCs) by physical insertion. The hADSCs coated by different GAGs were intravenously injected into mice, and the biodistribution of cells was analyzed by an In Vivo Imaging System (IVIS) to compare the effect of various GAGs on the modulation of biodistribution of stem cells. The results showed that all three GAGs could provide less entrapment in the lung but enhanced accumulation in the liver and spleen. Especially, HA- and heparin coating on hADSCs showed a 1.5-fold higher accumulation than CS-coating on hADSCs in the liver and spleen. Thus, lipid-conjugated HA and heparin are potentially useful coating materials for the liver or spleen-targeted delivery system of therapeutic stem cells. [Display omitted] •Lipid conjugated GAGs (hyaluronic acid (HA), chondroitin sulfate (CS), and heparin) were synthesized.•Stem cell was coated with lipid conjugated GAGs by physical insertion.•GAG coating resulted in enhanced accumulation in the liver and spleen but less entrapment in the lung upon i.v. injection.•HA and heparin coating induced higher accumulation in the liver than CS coating.