Optimizing cryopreservation conditions for use of fucosylated human mesenchymal stromal cells in anti-inflammatory/immunomodulatory therapeutics.

Mesenchymal stem/stromal cells (MSCs) are being increasingly used in cell-based therapies due to their broad anti-inflammatory and immunomodulatory properties. Intravascularly-administered MSCs do not efficiently migrate to sites of inflammation/immunopathology, but this shortfall has been overcome by cell surface enzymatic fucosylation to engender expression of the potent E-selectin ligand HCELL. In applications of cell-based therapies, cryopreservation enables stability in both storage and transport of the produced cells from the manufacturing facility to the point of care.

Enrichment and nLC-MS/MS Analysis of Head and Neck Cancer Mucinome Glycoproteins.

Mucin-domain glycoproteins expressed on cancer cell surfaces play central roles in cell adhesion, cancer progression, stem cell renewal, and immune evasion. Despite abundant evidence that mucin-domain glycoproteins are critical to the pathobiology of head and neck squamous cell carcinoma (HNSCC), our knowledge of the composition of that mucinome is grossly incomplete. Here, we utilized a catalytically inactive point mutant of the enzyme StcE (StcE) to capture mucin-domain glycoproteins in head and neck cancer cell line lysates followed by their characterization using sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), in-gel digestion, nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS), and enrichment analyses.

The biology of E-selectin ligands in leukemogenesis.

Both the cascade whereby a blood-borne cell enters a tissue and the anchoring of hematopoietic stem/progenitor cells (HSPCs) within bone marrow critically pivots on cell-cell interactions mediated by E-selectin binding to its canonical carbohydrate ligand, the tetrasaccharide termed "sialylated Lewis X" (sLeX). E-selectin, a member of the selectin class of adhesion molecules that is exclusively expressed by vascular endothelium, engages sLeX-bearing glycoconjugates that adorn mature leukocytes and HSPCs, as well as malignant cells, thereby permitting these cells to extravasate into various tissues. E-selectin expression is induced on microvascular endothelial cells within inflammatory loci at all tissues.

ABO blood group antigens and differential glycan expression: Perspective on the evolution of common human enzyme deficiencies.

Enzymes catalyze biochemical reactions and play critical roles in human health and disease. Enzyme variants and deficiencies can lead to variable expression of glycans, which can affect physiology, influence predilection for disease, and/or directly contribute to disease pathogenesis. Although certain well-characterized enzyme deficiencies result in overt disease, some of the most common enzyme deficiencies in humans form the basis of blood groups.