title: Mesenchymal stem cells contribute to endogenous FVIII:c production.
abstract: Besides the liver, it has been difficult to identify which organ(s) and/or cellular component(s) contribute significantly to the production of human FVIII:c (FVIII). Thus far, only endothelial cells have been shown to constitute a robust extrahepatic source of FVIII, possibly explaining both the diverse presence of FVIII mRNA in the body, and the observed increase in FVIII levels during liver failure. Here, we investigate whether human mesenchymal stem cells (MSC), ubiquitously present in different organs, could also contribute to FVIII production. MSC isolated from human lung, liver, brain, and bone marrow expressed FVIII message as determined by quantitative-RT-PCR. Using an antibody specific for FVIII, confocal microscopy, and umbilical cord-derived endothelial cells (HUVEC) as a negative control, we demonstrated that, in MSC, FVIII protein was not stored in granules; rather, it localized to the perinuclear region. Furthermore, functional FVIII was detected in MSC supernatants and cell lysates by aPTT and chromogenic assays. These results demonstrate that MSC can contribute at low levels to the functional FVIII pool, and advance the understanding of the physiology of FVIII production and secretion.
authors.affiliation: Department of Animal Biotechnology, University of Nevada, Reno, NV, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Sanada
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Kuo
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Colletti
authors.forename: Melisa
authors.initials: M
authors.lastname: Soland
authors.forename: Saloomeh
authors.initials: S
authors.lastname: Mokhtari
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Knovich
authors.forename: John
authors.initials: J
authors.lastname: Owen
authors.forename: Esmail D
authors.initials: ED
authors.lastname: Zanjani
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Porada
authors.forename: Graça
authors.initials: G
authors.lastname: Almeida-Porada
mesh_terms: D002454:Cell Differentiation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005169:Factor VIII / Q000096:biosynthesis* / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; C078147:F8 protein, human; D005169:Factor VIII