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Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone.

Publication ,  Journal Article
Sackstein, R; Merzaban, JS; Cain, DW; Dagia, NM; Spencer, JA; Lin, CP; Wohlgemuth, R
Published in: Nat Med
February 2008

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-selectin, 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 alpha-2,3-sialyl modifications. Using an alpha-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), 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.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

February 2008

Volume

14

Issue

2

Start / End Page

181 / 187

Location

United States

Related Subject Headings

  • Stromal Cells
  • Stress, Mechanical
  • Polysaccharides
  • N-Acetylneuraminic Acid
  • Multipotent Stem Cells
  • Middle Aged
  • Mice
  • Mesenchymal Stem Cells
  • Ligands
  • Immunology
 

Citation

APA
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ICMJE
MLA
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Sackstein, R., Merzaban, J. S., Cain, D. W., Dagia, N. M., Spencer, J. A., Lin, C. P., & Wohlgemuth, R. (2008). Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med, 14(2), 181–187. https://doi.org/10.1038/nm1703
Sackstein, Robert, Jasmeen S. Merzaban, Derek W. Cain, Nilesh M. Dagia, Joel A. Spencer, Charles P. Lin, and Roland Wohlgemuth. “Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone.Nat Med 14, no. 2 (February 2008): 181–87. https://doi.org/10.1038/nm1703.
Sackstein R, Merzaban JS, Cain DW, Dagia NM, Spencer JA, Lin CP, et al. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med. 2008 Feb;14(2):181–7.
Sackstein, Robert, et al. “Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone.Nat Med, vol. 14, no. 2, Feb. 2008, pp. 181–87. Pubmed, doi:10.1038/nm1703.
Sackstein R, Merzaban JS, Cain DW, Dagia NM, Spencer JA, Lin CP, Wohlgemuth R. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med. 2008 Feb;14(2):181–187.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

February 2008

Volume

14

Issue

2

Start / End Page

181 / 187

Location

United States

Related Subject Headings

  • Stromal Cells
  • Stress, Mechanical
  • Polysaccharides
  • N-Acetylneuraminic Acid
  • Multipotent Stem Cells
  • Middle Aged
  • Mice
  • Mesenchymal Stem Cells
  • Ligands
  • Immunology