Home LiteratureArticle Details
PMID: 18519682 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Long-term in vitro expansion alters the biology of adult mesenchymal stem cells.

Cancer research ·Vol. 68 ·No. 11 ·2008-06-01 ·Pages 4229-38

Izadpanah R, Kaushal D, Kriedt C, Tsien F, Patel B, Dufour J, Bunnell BA

Abstract

Mesenchymal stem cells (MSC) derived from bone marrow stem cells (BMSC) and adipose tissue stem cells (ASC) of humans and rhesus macaques were evaluated for their cell cycle properties during protracted culture in vitro. Human ASCs (hASC) and rhesus BMSCs (rBMSC) underwent significantly more total population doublings than human BMSCs (hBMSC) and rhesus ASCs (rASC). The cell cycle profile of all MSCs was altered as cultures aged. hMSCs underwent an increase in the frequency of cells in the S phase at P20 and P30. However, rhesus MSCs from both sources developed a distinct polyploid population of cells at P20, which progressed to aneuploidy by P30. Karyotype analysis of MSCs revealed the development of tetraploid or aneuploid karyotypes in the rhesus cells at P20 or P30. Analysis of the transcriptome of the MSCs from early and late passages revealed significant alterations in the patterns of gene expression (8.8% of the genes were differentially expressed in hBMSCs versus hASCs, and 5.5% in rBMSCs versus rASCs). Gene expression changes were much less evident within the same cell type as aging occurred (0.7% in hMSCs and 0.9% in rMSC). Gene ontology analysis showed that functions involved in protein catabolism and regulation of pol II transcription were overrepresented in rASCs, whereas the regulation of I kappa B/nuclear factor-kappaB cascade were overrepresented in hBMSCs. Functional analysis of genes that were differentially expressed in rASCs and hBMSCs revealed that pathways involved in cell cycle, cell cycle checkpoints, protein-ubiquitination, and apoptosis were altered.

MeSH Terms
Adult Blotting, Western Cell Cycle Cell Differentiation Humans Karyotyping Mesenchymal Stem Cells/pathology
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Izadpanah Reza
Division of Gene Therapy, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana 70433, USA.
Kaushal Deepak
Kriedt Christopher
Tsien Fern
Patel Bindiya
Dufour Jason
Bunnell Bruce A
References (40)
40 references, click to expand
  1. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart.
    Circulation. 2002 Jan 1;105(1):93-8 PMID: 11772882
  2. Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5093-8 PMID: 11309484
  3. Defective osteogenesis of the stromal stem cells predisposes CD18-null mice to osteoporosis.
    Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14022-7 PMID: 16172402
  4. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis.
    J Neurosci Res. 2002 Sep 15;69(6):908-17 PMID: 12205683
  5. A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9363-7 PMID: 7568133
  6. Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells.
    Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9819-24 PMID: 12119403
  7. Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection.
    Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31-6 PMID: 11134512
  8. Comment on " 'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature".
    Science. 2003 Oct 17;302(5644):393; author reply 393 PMID: 14563990
  9. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue.
    Stem Cells. 2006 May;24(5):1294-301 PMID: 16410387
  10. Elevated gene expression levels distinguish human from non-human primate brains.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13030-5 PMID: 14557539
  11. Construction and analysis of a human-chimpanzee comparative clone map.
    Science. 2002 Jan 4;295(5552):131-4 PMID: 11778049
  12. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells.
    Nature. 2005 Oct 13;437(7061):1043-7 PMID: 16222300
  13. Multistep carcinogenesis: a chain reaction of aneuploidizations.
    Cell Cycle. 2003 May-Jun;2(3):202-10 PMID: 12734426
  14. Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles.
    Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2957-62 PMID: 14976249
  15. Comparison of non-human primate and human whole blood tissue gene expression profiles.
    Toxicol Sci. 2005 Sep;87(1):306-14 PMID: 15976184
  16. Switching and signaling at the telomere.
    Cell. 2001 Sep 21;106(6):661-73 PMID: 11572773
  17. Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae.
    Cell. 2001 Feb 9;104(3):397-408 PMID: 11239397
  18. Pluripotency of mesenchymal stem cells derived from adult marrow.
    Nature. 2002 Jul 4;418(6893):41-9 PMID: 12077603
  19. Marrow stromal cells as stem cells for nonhematopoietic tissues.
    Science. 1997 Apr 4;276(5309):71-4 PMID: 9082988
  20. Spontaneous human adult stem cell transformation.
    Cancer Res. 2005 Apr 15;65(8):3035-9 PMID: 15833829
  21. Multilineage cells from human adipose tissue: implications for cell-based therapies.
    Tissue Eng. 2001 Apr;7(2):211-28 PMID: 11304456
  22. G1 tetraploidy checkpoint and the suppression of tumorigenesis.
    J Cell Biochem. 2003 Mar 1;88(4):673-83 PMID: 12577301
  23. Characterization of multipotent mesenchymal stem cells from the bone marrow of rhesus macaques.
    Stem Cells Dev. 2005 Aug;14(4):440-51 PMID: 16137233
  24. Intra- and interspecific variation in primate gene expression patterns.
    Science. 2002 Apr 12;296(5566):340-3 PMID: 11951044
  25. Patterns of gene expression in peripheral blood mononuclear cells of rhesus macaques infected with SIVmac251 and exhibiting differential rates of disease progression.
    AIDS Res Hum Retroviruses. 2003 May;19(5):369-87 PMID: 12803996
  26. Human adipose tissue is a source of multipotent stem cells.
    Mol Biol Cell. 2002 Dec;13(12):4279-95 PMID: 12475952
  27. Aging of mesenchymal stem cell in vitro.
    BMC Cell Biol. 2006 Mar 10;7:14 PMID: 16529651
  28. BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells.
    Biochem Biophys Res Commun. 2001 Jun 8;284(2):411-8 PMID: 11394894
  29. Transcriptome profiles of host gene expression in a monkey model of human malaria.
    J Infect Dis. 2005 Feb 1;191(3):400-9 PMID: 15633100
  30. Global genomic changes induced by two-stage carcinogen exposure are precancerous alterations in non-transformed human liver epithelial THLE-3 cells.
    Int J Oncol. 2005 Oct;27(4):925-31 PMID: 16142307
  31. The cell cycle.
    Stem Cells. 2001;19(1):88-91 PMID: 11209094
  32. Pathways governing G1/S transition and their response to DNA damage.
    FEBS Lett. 2001 Feb 16;490(3):117-22 PMID: 11223026
  33. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells.
    EMBO J. 2002 Feb 15;21(4):483-92 PMID: 11847097
  34. Chk1 and Chk2 kinases in checkpoint control and cancer.
    Cancer Cell. 2003 May;3(5):421-9 PMID: 12781359
  35. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue.
    J Cell Biochem. 2006 Dec 1;99(5):1285-97 PMID: 16795045
  36. The significance of unstable chromosomes in colorectal cancer.
    Nat Rev Cancer. 2003 Sep;3(9):695-701 PMID: 12951588
  37. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines.
    Nature. 2005 Oct 13;437(7061):1038-42 PMID: 16222248
  38. The serial cultivation of human diploid cell strains.
    Exp Cell Res. 1961 Dec;25:585-621 PMID: 13905658
  39. Analysis of result variability from high-density oligonucleotide arrays comparing same-species and cross-species hybridizations.
    Biotechniques. 2002 Sep;33(3):516-8, 520, 522 passim PMID: 12238761
  40. Crosstalk of the mitotic spindle assembly checkpoint with p53 to prevent polyploidy.
    Oncogene. 2004 Sep 9;23(41):6845-53 PMID: 15286707
Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-07-5272
Published
2008-06-01
Pages
4229-38
Language
English
Region
United States
NLM ID
2984705R
PMCID
PMC2713721
Subset
IM
Grants
NCRR NIH HHS · P51 RR000164 · United States
NCRR NIH HHS · P51 RR000164-467149 · United States
NCRR NIH HHS · RR00164 · United States
External Links
PubMed source DOI: 10.1158/0008-5472.CAN-07-5272 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2