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Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration
1Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. Rsackstein@rics.bwh.harvard.edu
Immunological Reviews
|July 15, 2009
Summary
This study details the engineering of CD44 into hematopoietic cell E-/L-selectin ligand (HCELL), a potent cell adhesion molecule. This glycan engineering advances cell delivery for therapies by enhancing vascular targeting.
Area of Science:
- Cardiovascular Biology
- Immunology
- Glycobiology
Background:
- Vertebrate cardiovascular systems require efficient cell recruitment to sites of inflammation or injury.
- High blood flow necessitates specialized cell surface molecules for shear-resistant adhesion and extravasation.
- Selectins, a family of C-type lectins, mediate these interactions by binding sialofucosylated glycans.
Purpose of the Study:
- To explain the design of reagents for converting native CD44 into the HCELL glycoform.
- To describe how ex vivo glycan engineering of HCELL can improve cell delivery for therapies.
Main Methods:
- Engineering of native CD44 into the HCELL glycoform.
- Ex vivo glycan engineering of HCELL expression.
Main Results:
- Demonstration of reagents to convert CD44 to HCELL, a potent E-selectin counter-receptor.
- Potential for ex vivo HCELL engineering to facilitate efficient vascular delivery of cells.
Conclusions:
- HCELL is the most potent E-selectin counter-receptor on human cells.
- Ex vivo glycan engineering of HCELL offers a promising strategy for cell-based therapies.
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