title: Expression of blood group genes by mesenchymal stem cells.
abstract: Incompatible blood group antigens are highly immunogenic and can cause graft rejections. Focusing on distinct carbohydrate- and protein-based membrane structures, defined by blood group antigens, we investigated human bone marrow-derived mesenchymal stem cells (MSCs) cultured in human serum. The presence of H (CD173), ABO, RhD, RhCE, RhAG, Kell, urea transporter type B (SLC14A1, previously known as JK), and Duffy antigen receptor of chemokines (DARC) was evaluated at the levels of genome, transcriptome and antigen. Fucosyltransferase-1 (FUT1), RHCE, KEL, SLC14A1 (JK) and DARC mRNA were transcribed in MSCs. FUT1 mRNA transcription was lost during differentiation. The mRNA transcription of SLC14A1 (JK) decreased during chondrogenic differentiation, while that of DARC increased during adipogenic differentiation. All MSCs synthesized SLC14A1 (JK) but no DARC protein. However, none of the protein antigens tested occurred on the surface, indicating a lack of associated protein function in the membrane. As A and B antigens are neither expressed nor adsorbed, concerns of ABO compatibility with human serum supplements during culture are alleviated. The H antigen expression by GD2dim+ MSCs identified two distinct MSC subpopulations and enabled their isolation. We hypothesize that GD2(dim+) H(+) MSCs retain a better 'stemness'. Because immunogenic blood group antigens are lacking, they cannot affect MSC engraftment in vivo, which is promising for clinical applications.
authors.affiliation: Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Schäfer
authors.forename: Martina
authors.initials: M
authors.lastname: Schnaidt
authors.forename: Roland A
authors.initials: RA
authors.lastname: Klaffschenkel
authors.forename: Georg
authors.initials: G
authors.lastname: Siegel
authors.forename: Michael
authors.initials: M
authors.lastname: Schüle
authors.forename: Maria Anna
authors.initials: MA
authors.lastname: Rädlein
authors.forename: Ursula
authors.initials: U
authors.lastname: Hermanutz-Klein
authors.forename: Miriam
authors.initials: M
authors.lastname: Ayturan
authors.forename: Marine
authors.initials: M
authors.lastname: Buadze
authors.forename: Christoph
authors.initials: C
authors.lastname: Gassner
authors.forename: Lusine
authors.initials: L
authors.lastname: Danielyan
authors.forename: Torsten
authors.initials: T
authors.lastname: Kluba
authors.forename: Hinnak
authors.initials: H
authors.lastname: Northoff
authors.forename: Willy A
authors.initials: WA
authors.lastname: Flegel
mesh_terms: D000017:ABO Blood-Group System / Q000378:metabolism; D001789:Blood Group Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004375:Duffy Blood-Group System / Q000096:biosynthesis / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D000096982:Urea Transporters
chemical_list: D000017:ABO Blood-Group System; D001789:Blood Group Antigens; D004375:Duffy Blood-Group System; D005732:Gangliosides; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000096982:Urea Transporters; C473745:ACKR1 protein, human; C019403:ganglioside, GD2