Letter abstract
Nature Medicine 14, 181 - 187 (2008)
Published online: 13 January 2008 | doi:10.1038/nm1703
Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone
Robert Sackstein1,2, Jasmeen S Merzaban1, Derek W Cain1, Nilesh M Dagia1, Joel A Spencer3, Charles P Lin3 & Roland Wohlgemuth4
The capacity to direct migration ('homing') of blood-borne cells to a predetermined anatomic compartment is vital to stem cell–based tissue engineering and other adoptive cellular therapies. Although multipotent mesenchymal stromal cells (MSCs, also termed 'mesenchymal stem cells') hold the potential for curing generalized skeletal diseases, their clinical effectiveness is constrained by the poor osteotropism of infused MSCs (refs. 1–3). Cellular recruitment to bone occurs within specialized marrow vessels that constitutively express vascular E-selectin4, 5, a lectin that recognizes sialofucosylated determinants on its various ligands. We show here that human MSCs do not express E-selectin ligands, but express a CD44 glycoform bearing 
-2,3-sialyl modifications. Using an -1,3-fucosyltransferase preparation and enzymatic conditions specifically designed for treating live cells, we converted the native CD44 glycoform on MSCs into hematopoietic cell E-selectin/L-selectin ligand (HCELL)6, which conferred potent E-selectin binding without effects on cell viability or multipotency. Real-time intravital microscopy in immunocompromised (NOD/SCID) mice showed that intravenously infused HCELL+ MSCs infiltrated marrow within hours of infusion, with ensuing rare foci of endosteally localized cells and human osteoid generation. These findings establish that the HCELL glycoform of CD44 confers tropism to bone and unveil a readily translatable roadmap for programming cellular trafficking by chemical engineering of glycans on a distinct membrane glycoprotein.
- Departments of Dermatology and Medicine, Brigham and Women's Hospital and Harvard Skin Disease Research Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Research Specialties, Sigma-Aldrich, Buchs CH-9470, Switzerland.
Correspondence to: Robert Sackstein1,2 e-mail: rsackstein@rics.bwh.harvard.edu
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