Targeted systemic mesenchymal stem cell delivery using hyaluronate - wheat germ agglutinin conjugate.

Abstract

A variety of receptors for hyaluronate (HA), a natural linear polysaccharide, were found in the body, which have been exploited as target sites for HA-based drug delivery systems. In this work, mesenchymal stem cells (MSCs) were surface-modified with HA - wheat germ agglutinin (WGA) conjugate for targeted systemic delivery of MSCs to the liver. WGA was conjugated to HA by coupling reaction between aldehyde-modified HA and amine group of WGA. The conjugation of WGA to HA was corroborated by gel permeation chromatography (GPC) and the successful surface modification of MSCs with HA-WGA conjugate was confirmed by confocal microscopy. The synthesized HA-WGA conjugate could be incorporated onto the cellular membrane by agglutinating the cell-associated carbohydrates. Fluorescent imaging for in vivo biodistribution visualized the targeted delivery of the HA-WGA/MSC complex to the liver after intravenous injection. This new strategy for targeted delivery of MSCs using HA-WGA conjugate might be successfully exploited for various regenerative medicines including cell therapy.