title: Mesenchymal stem cell treatment for hemophilia: a review of current knowledge.
abstract: Hemophilia remains a non-curative disease, and patients are constrained to undergo repeated injections of clotting factors. In contrast, the sustained production of endogenous factors VIII (FVIII) or IX (FIX) by the patient's own cells could represent a curative treatment. Gene therapy has thus provided new hope for these patients. However, the issues surrounding the durability of expression and immune responses against gene transfer vectors remain. Cell therapy, involving stem cells expanded in vitro, can provide de novo protein synthesis and, if implanted successfully, could induce a steady-state production of low quantities of factors, which may keep the patient above the level required to prevent spontaneous bleeding. Liver-derived stem cells are already being assessed in clinical trials for inborn errors of metabolism and, in view of their capacity to produce FVIII and FIX in cell culture, they are now also being considered for clinical application in hemophilia patients.
authors.affiliation: Service de gastroentérologie et hépatologie pédiatrique, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Cliniques St Luc, Brussels, Belgium.
authors.forename: E M
authors.initials: EM
authors.lastname: Sokal
authors.affiliation: Université Catholique de Louvain, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Lombard
authors.affiliation: Division of Medicine, Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Mazza
mesh_terms: D000818:Animals; D000067128:Extracellular Vesicles / Q000378:metabolism; D005164:Factor IX / Q000096:biosynthesis* / Q000235:genetics; D005169:Factor VIII / Q000096:biosynthesis* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000601:surgery*; D006470:Hemorrhage / Q000517:prevention & control*; D006487:Hemostasis; D006801:Humans; D008099:Liver / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: C078147:F8 protein, human; D005169:Factor VIII; D005164:Factor IX
keywords: exosomes; hemophilia A; inborn errors; liver; metabolism; stem cells