Systematic chromosomal aberrations found in murine bone marrow-derived mesenchymal stem cells - PubMed

Affiliations

• PMID: 20109032
• DOI: 10.1089/scd.2009.0264

Systematic chromosomal aberrations found in murine bone marrow-derived mesenchymal stem cells

Claire Josse et al. Stem Cells Dev. 2010 Aug.

Abstract

Mesenchymal stem cells (MSCs) are studied as a cellular source for the treatment of various diseases. In this work, we isolated and cultivated murine bone marrow-derived MSCs. After a first observation of a solid tumor in a mouse injected with these cells, we systematically explored their chromosomal stability. We observed in all the cytogenetically analyzed cases gross chromosomal alterations every time the MSCs went through the senescence crisis while the lymphocytes from the same animals showed a normal chromosome count. This observation was confirmed in different mouse strains, with different culture protocols, and even in short-term cultures after a hematopoietic cell negative immunodepletion performed in order to accelerate the isolation procedure. Therefore, we conclude that murine MSCs display high chromosomal instability and can generate tumors, and that care must be taken before using them for the evaluation of MSC therapeutic potential.

Similar articles

• Detection of spontaneous tumorigenic transformation during culture expansion of human mesenchymal stromal cells.

  Pan Q, Fouraschen SM, de Ruiter PE, Dinjens WN, Kwekkeboom J, Tilanus HW, van der Laan LJ. Pan Q, et al. Exp Biol Med (Maywood). 2014 Jan;239(1):105-15. doi: 10.1177/1535370213506802. Epub 2013 Nov 13. Exp Biol Med (Maywood). 2014. PMID: 24227633 Clinical Trial.

• In vitro expanded bone marrow-derived murine (C57Bl/KaLwRij) mesenchymal stem cells can acquire CD34 expression and induce sarcoma formation in vivo.

  Xu S, De Becker A, De Raeve H, Van Camp B, Vanderkerken K, Van Riet I. Xu S, et al. Biochem Biophys Res Commun. 2012 Aug 3;424(3):391-7. doi: 10.1016/j.bbrc.2012.06.118. Epub 2012 Jul 6. Biochem Biophys Res Commun. 2012. PMID: 22771324

• Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation.

  Miura M, Miura Y, Padilla-Nash HM, Molinolo AA, Fu B, Patel V, Seo BM, Sonoyama W, Zheng JJ, Baker CC, Chen W, Ried T, Shi S. Miura M, et al. Stem Cells. 2006 Apr;24(4):1095-103. doi: 10.1634/stemcells.2005-0403. Epub 2005 Nov 10. Stem Cells. 2006. PMID: 16282438

• Controversies about the chromosomal stability of cultivated mesenchymal stem cells: their clinical use is it safe?

  Ferreira RJ, Irioda AC, Cunha RC, Francisco JC, Guarita-Souza LC, Srikanth GV, Nityanand S, Rosati R, Chachques JC, de Carvalho KA. Ferreira RJ, et al. Curr Stem Cell Res Ther. 2012 Sep;7(5):356-63. doi: 10.2174/157488812802481472. Curr Stem Cell Res Ther. 2012. PMID: 22834994 Review.

Cited by

• Isolation of mouse mesenchymal stem cells with normal ploidy from bone marrows by reducing oxidative stress in combination with extracellular matrix.

  Fan G, Wen L, Li M, Li C, Luo B, Wang F, Zhou L, Liu L. Fan G, et al. BMC Cell Biol. 2011 Jul 6;12:30. doi: 10.1186/1471-2121-12-30. BMC Cell Biol. 2011. PMID: 21729331 Free PMC article.

• In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

  Wislet-Gendebien S, Poulet C, Neirinckx V, Hennuy B, Swingland JT, Laudet E, Sommer L, Shakova O, Bours V, Rogister B. Wislet-Gendebien S, et al. PLoS One. 2012;7(10):e46425. doi: 10.1371/journal.pone.0046425. Epub 2012 Oct 5. PLoS One. 2012. PMID: 23071568 Free PMC article.

• Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture.

  Buddingh EP, Ruslan SEN, Reijnders CMA, Szuhai K, Kuijjer ML, Roelofs H, Hogendoorn PCW, Maarten Egeler R, Cleton-Jansen AM, Lankester AC. Buddingh EP, et al. Clin Sarcoma Res. 2015 Jun 23;5:16. doi: 10.1186/s13569-015-0031-1. eCollection 2015. Clin Sarcoma Res. 2015. PMID: 26106474 Free PMC article.

• Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington's disease.

  Olson SD, Pollock K, Kambal A, Cary W, Mitchell GM, Tempkin J, Stewart H, McGee J, Bauer G, Kim HS, Tempkin T, Wheelock V, Annett G, Dunbar G, Nolta JA. Olson SD, et al. Mol Neurobiol. 2012 Feb;45(1):87-98. doi: 10.1007/s12035-011-8219-8. Epub 2011 Dec 9. Mol Neurobiol. 2012. PMID: 22161544 Free PMC article. Review.

• Untangling the response of bone tumor cells and bone forming cells to matrix stiffness and adhesion ligand density by means of hydrogels.

  Jiang T, Zhao J, Yu S, Mao Z, Gao C, Zhu Y, Mao C, Zheng L. Jiang T, et al. Biomaterials. 2019 Jan;188:130-143. doi: 10.1016/j.biomaterials.2018.10.015. Epub 2018 Oct 15. Biomaterials. 2019. PMID: 30343256 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon