4.7 Article

Engineered cell homing

Journal

BLOOD
Volume 118, Issue 25, Pages E184-E191

Publisher

AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-10-311464

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Funding

  1. American Heart Association [0970178N]
  2. National Institutes of Health [DE019191, HL095722, HL097172]
  3. Massachusetts Institute of Technology
  4. Kauffman Foundation
  5. Human Frontier Science Program (Postdoctoral Fellowship)

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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 MSCbased 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 Lewis(x) (sLe(x)) 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. (Blood. 2011; 118(25): e184-e191)

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