title: Stem cell enrichment with selectin receptors: mimicking the pH environment of trauma.
abstract: The isolation of hematopoietic stem and progenitor cells (HSPCs) is critical for transplantation therapy and HSPC research, however current isolation techniques can be prohibitively expensive, time-consuming, and produce variable results. Selectin-coated microtubes have shown promise in rapidly isolating HSPCs from human bone marrow, but further purification of HSPCs remains a challenge. Herein, a biomimetic device for HSPC isolation is presented to mimic the acidic vascular microenvironment during trauma, which can enhance the binding frequency between L-selectin and its counter-receptor PSGL-1 and HSPCs. Under acidic pH conditions, L-selectin coated microtubes enhanced CD34+ HSPC adhesion, as evidenced by decreased cell rolling velocity and increased rolling flux. Dynamic light scattering was utilized as a novel sensor to confirm an L-selectin conformational change under acidic conditions, as previously predicted by molecular dynamics. These results suggest that mimicking the acidic conditions of trauma can induce a conformational extension of L-selectin, which can be utilized for flow-based, clinical isolation of HSPCs.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA. mike.king@cornell.edu.
authors.forename: Thong M
authors.initials: TM
authors.lastname: Cao
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mitchell
authors.forename: Jane
authors.initials: J
authors.lastname: Liesveld
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
mesh_terms: D002469:Cell Separation / Q000295:instrumentation*; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019041:L-Selectin / Q000737:chemistry / Q000276:immunology*; D015854:Up-Regulation; D014947:Wounds and Injuries / Q000276:immunology* / Q000473:pathology*
chemical_list: D019041:L-Selectin
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