Comprehensive transcriptome and immunophenotype analysis of renal and cardiac MSC-like populations supports strong congruence with bone marrow MSC despite maintenance of distinct identities

Pelekanos, Rebecca A., Li, Joan, Gongora, Milena, Chandrakanthan, Vashe, Scown, Janelle, Suhaimi, Norseha, Gary Brooke, Christensen, Melinda E., Doan, Tram, Rice, Alison M., Osborne, Geoffrey W., Grimmond, Sean M., Harvey, Richard P., Atkinson, Kerry and Little, Melissa H. (2012) Comprehensive transcriptome and immunophenotype analysis of renal and cardiac MSC-like populations supports strong congruence with bone marrow MSC despite maintenance of distinct identities. Stem Cell Research, 8 1: 58-73. doi:10.1016/j.scr.2011.08.003

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Author Pelekanos, Rebecca A.
Li, Joan
Gongora, Milena
Chandrakanthan, Vashe
Scown, Janelle
Suhaimi, Norseha
Gary Brooke
Christensen, Melinda E.
Doan, Tram
Rice, Alison M.
Osborne, Geoffrey W.
Grimmond, Sean M.
Harvey, Richard P.
Atkinson, Kerry
Little, Melissa H.
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
Journal name Stem Cell Research   Check publisher's open access policy
ISSN 1873-5061
1876-7753
Publication date 2012-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.scr.2011.08.003
Open Access Status DOI
Volume 8
Issue 1
Start page 58
End page 73
Total pages 16
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Subject 1309 Developmental Biology
1307 Cell Biology
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). It lumina 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. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
Formatted 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.
Keyword Cell & Tissue Engineering
Biotechnology & Applied Microbiology
Cell Biology
Cell Biology
Biotechnology & Applied Microbiology
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
CELL & TISSUE ENGINEERING
CELL BIOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 17 August 2011

 
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