title: CD44 fucosylation on mesenchymal stem cell enhances homing and macrophage polarization in ischemic kidney injury.
abstract: The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent E-selectin affinity might enhance the homing and regenerative abilities of MSCs. Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N-glycans of CD44 to become HCELL positive, thus interacting with E-selectin on injured endothelial cells. HCELL expression facilitated MSC homing in kidneys within 24h after injury and reduced lung stasis. An in vitro adhesion assay revealed that transfection enhanced the association between MSCs and hypoxic endothelial cells. In mice treated with HCELL-positive MSCs, the injured kidneys exhibited clusters of homing MSCs, whereas MSCs were rarely observed in mouse kidneys treated with HCELL-negative MSCs. Most MSCs were initially localized at the renal capsule, and some MSCs later migrated inward between tubules. Most homing MSCs were in close contact with inflammatory cells without tubular transdifferentiation. Furthermore, HCELL-positive MSCs substantially alleviated renal injury, partly by enhancing the polarization of infiltrating macrophages. In conclusion, engineering the glycan of CD44 on MSCs through FTVI transfection might enhance renotropism and the regenerating ability of MSCs in ischemic kidney injury.
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kang-Ju
authors.initials: KJ
authors.lastname: Chou
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Po-Tsang
authors.initials: PT
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: hcfang@vghks.gov.tw.
authors.forename: Hua-Chang
authors.initials: HC
authors.lastname: Fang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D054338:Cell Transdifferentiation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D007668:Kidney / Q000293:injuries / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL
chemical_list: D018960:Hyaluronan Receptors
keywords: Bone-marrow-derived mesenchymal stem cells; Hematopoietic cell E-/L-selectin ligand; Ischemic kidney injury; Macrophage polarization