Authors:
Debanjan Sarkar, Joel A. Spencer, Joseph A. Phillips, Weian Zhao, Sebastian Schafer, Dawn P. Spelke, Luke J. Mortensen, Juan P. Ruiz, Praveen Kumar Vemula, Rukmani Sridharan, Sriram Kumar, Rohit Karnik, Charles P. Lin, and Jeffrey M. Karp
Summary:
One of the greatest challenges in cell therapy is to minimally invasively deliver a large quantity of viable cells to a tissue of interest with high engraftment efficiency. Low and inefficient homing of systemically delivered mesenchymal stem cells (MSCs), for example, is thought to be a major limitation of existing MSC-based therapeutic approaches, caused predominantly by inadequate expression of cell surface adhesion receptors. Using a platform approach that preserves the MSC phenotype and does not require genetic manipulation, we modified the surface of MSCs with a nanometer-scale polymer construct containing sialyl Lewisx (sLex) that is found on the surface of leukocytes and mediates cell rolling within inflamed tissue. The sLex engineered MSCs exhibited a robust rolling response on inflamed endothelium in vivo and homed to inflamed tissue with higher efficiency compared with native MSCs. The modular approach described herein offers a simple method to potentially target any cell type to specific tissues via the circulation.
Source:
Blood; Vol. 118, No. 25, e184-e191 (12/15/11)