Engineered cell homing

Blood. 2011 Dec 15;118(25):e184-91. doi: 10.1182/blood-2010-10-311464. Epub 2011 Oct 27.

Abstract

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 Lewis(x) (sLe(x)) that is found on the surface of leukocytes and mediates cell rolling within inflamed tissue. The sLe(x) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism
  • Dinoprostone / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HL-60 Cells
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Integrin beta1 / metabolism
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Oligosaccharides / chemistry*
  • Selectins / metabolism
  • Sialyl Lewis X Antigen
  • Thy-1 Antigens / metabolism
  • Transplantation, Heterologous

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Integrin beta1
  • Oligosaccharides
  • Selectins
  • Sialyl Lewis X Antigen
  • Thy-1 Antigens
  • Insulin-Like Growth Factor I
  • Dinoprostone