title: Comprehensive transcriptome and immunophenotype analysis of renal and cardiac MSC-like populations supports strong congruence with bone marrow MSC despite maintenance of distinct identities.
abstract: Cells resembling bone marrow mesenchymal stem cells (MSC) have been isolated from many organs but their functional relationships have not been thoroughly examined. Here we compared the immunophenotype, gene expression, multipotency and immunosuppressive potential of MSC-like colony-forming cells from adult murine bone marrow (bmMSC), kidney (kCFU-F) and heart (cCFU-F), cultured under uniform conditions. All populations showed classic MSC morphology and in vitro mesodermal multipotency. Of the two solid organ-specific CFU-F, only kCFU-F displayed suppression of T-cell alloreactivity in vitro, albeit to a lesser extent than bmMSC. Quantitative immunophenotyping using 81 phycoerythrin-conjugated CD antibodies demonstrated that all populations contained high percentages of cells expressing diagnostic MSC surface markers (Sca1, CD90.2, CD29, CD44), as well as others noted previously on murine MSC (CD24, CD49e, CD51, CD80, CD81, CD105). Illumina microarray expression profiling and bioinformatic analysis indicated a correlation of gene expression of 0.88-0.92 between pairwise comparisons. All populations expressed approximately 66% of genes in the pluripotency network (Plurinet), presumably reflecting their stem-like character. Furthermore, all populations expressed genes involved in immunomodulation, homing and tissue repair, suggesting these as conserved functions for MSC-like cells in solid organs. Despite this molecular congruence, strong biases in gene and protein expression and pathway activity were seen, suggesting organ-specific functions. Hence, tissue-derived MSC may also retain unique properties potentially rendering them more appropriate as cellular therapeutic agents for their organ of origin.
authors.affiliation: Australian Stem Cell Centre, Monash University, Clayton, Victoria, Australia.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Pelekanos
authors.forename: Joan
authors.initials: J
authors.lastname: Li
authors.forename: Milena
authors.initials: M
authors.lastname: Gongora
authors.forename: Vashe
authors.initials: V
authors.lastname: Chandrakanthan
authors.forename: Janelle
authors.initials: J
authors.lastname: Scown
authors.forename: Norseha
authors.initials: N
authors.lastname: Suhaimi
authors.forename: Gary
authors.initials: G
authors.lastname: Brooke
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Christensen
authors.forename: Tram
authors.initials: T
authors.lastname: Doan
authors.forename: Alison M
authors.initials: AM
authors.lastname: Rice
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Osborne
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: Kerry
authors.initials: K
authors.lastname: Atkinson
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Little
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D048430:Cell Shape; D003114:Colony-Forming Units Assay; D000939:Epitopes / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D016130:Immunophenotyping / Q000379:methods*; D007165:Immunosuppression Therapy; D007668:Kidney / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000166:cytology*; D009928:Organ Specificity / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*
chemical_list: D000939:Epitopes; D012333:RNA, Messenger