Engineered cell homing.
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.
Center for Regenerative Therapeutics and Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, 65 Landsdowne St., Cambridge, MA 02139, USA.
Debanjan
D
Sarkar
Joel A
JA
Spencer
Joseph A
JA
Phillips
Weian
W
Zhao
Sebastian
S
Schafer
Dawn P
DP
Spelke
Luke J
LJ
Mortensen
Juan P
JP
Ruiz
Praveen Kumar
PK
Vemula
Rukmani
R
Sridharan
Sriram
S
Kumar
Rohit
R
Karnik
Charles P
CP
Lin
Jeffrey M
JM
Karp
D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000737:chemistry*; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D018800:Thy-1 Antigens / Q000378:metabolism; D014183:Transplantation, Heterologous
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019012:Integrin beta1; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D018800:Thy-1 Antigens; D007334:Insulin-Like Growth Factor I; D015232:Dinoprostone