Stem Cell Activation Technique Works Well in Tissue Cultures

A novel method for covalently binding a specific sugar molecule to the surface of mesenchymal stem cell (MSCs) is designed to induce the stem cells to leave the blood stream and migrate to sites of injury where they can differentiate to replace damaged tissue.

Investigators at the Harvard-MIT Division of Health Sciences and Technology (Cambridge, MA, USA focused on one of the main unsolved problems in the field of stem cell therapy: "Delivery remains one of the biggest hurdles to stem cell therapy,” explained senior instructor Dr. Jeffrey Karp. "The blood stream offers a natural delivery vehicle, but stem cells do not move through blood vessels normally after being expanded in culture.”

Dr. Karp is senior author on a paper published in the October 31, 2008, online edition of the journal Bioconjugate Chemistry that described a method for chemically modifying the surface of MSCs to induce them to travel to their intended targets.

The method is based on three components: avidin, biotin, and a tetrasaccharide carbohydrate called SLeX (Sialyl LewisX). SLeX is usually attached to O-glycans on the surface of cells, and is known to play a vital role in cell-cell recognition processes. It is one of the most important blood group antigens and is displayed on the terminus of glycolipids that are present on the cell-surface. Resting T and B-lymphocytes lack its expression and they are induced to strongly express SLeX upon activation. MSCs do not display SLeX on their cell surface.

The activation technique involved flooding a culture dish of MSCs with the three molecules--biotin, streptavidin, and SleX--one after the other. The biotin formed a strong bond with the streptavidin, and the complex anchored SLeX to the cell surface. The concentrations of each molecule were adjusted to maximize the cell's ability to roll along the interior of blood vessels, rather than getting lost in the flow.

The technique worked well in tissue culture; "We need to confirm that this rolling behavior translates into increased homing and tissue repair,” said Dr. Karp. "We may need to tweak the cells further.”

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Harvard-MIT Division of Health Sciences and Technology