Abstract
Injection into the heart tissue is a direct route for optimally placing mesenchymal stem cells (MSCs) to regulate local inflammation following a heart attack. The retention of MSCs at the injection site is severely limited by the fluid flows that rapidly wash cells away and minimize their capacity to modulate cardiac inflammation. To prevent this loss of MSCs and their function, antibody coatings were designed for the surface of MSCs to enhance their adhesion to the inflamed tissue. MSCs were biotinylated, and biotinylated antibodies against intercellular cell adhesion molecules were conjugated to the cell surface through an intermediate layer of streptavidin. MSC surfaces were modified with ∼7000 biotin/μm2 and ∼23 antibodies/μm2. The heart tissue injection of antibody-coated MSCs offered a 3-fold increase of cell retention in an infarcted heart over the injection of uncoated MSCs. We supported the mechanism of adhesion through the analysis of MSC adhesion to inflamed endothelial cells and also surfaces of purified adhesion molecules on glass under microfluidic shear flow.
| Original language | English |
|---|---|
| Pages (from-to) | 2930-2939 |
| Number of pages | 10 |
| Journal | ACS Applied Bio Materials |
| Volume | 3 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 18 2020 |
Bibliographical note
Funding Information:This work was partially supported by R01 HL127682 and the National Science Foundation under Award CBET-1351531. Dr. Abdel-Latif is supported by the University of Kentucky COBRE Early Career Program (P20 GM103527) and the NIH Grant R01 HL138488.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
Keywords
- ICAM1 antibody
- cell surface coating
- endothelium targeting
- intramyocardial delivery
- targeted cell delivery
ASJC Scopus subject areas
- Biochemistry, medical
- Chemistry (all)
- Biomedical Engineering
- Biomaterials