Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung

Aguilar, Susana, Nye, Emma, Chan, Jerry, Loebinger, Michael, Spencer-Dene, Bradley, Fisk, Nick, Stamp, Gordon, Bonnet, Dominique and Janes, Sam M. (2007) Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung. Stem Cells, 25 6: 1586-1594. doi:10.1634/stemcells.2006-0762


Author Aguilar, Susana
Nye, Emma
Chan, Jerry
Loebinger, Michael
Spencer-Dene, Bradley
Fisk, Nick
Stamp, Gordon
Bonnet, Dominique
Janes, Sam M.
Title Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
1549-4918
Publication date 2007-06-01
Year available 2007
Sub-type Article (original research)
DOI 10.1634/stemcells.2006-0762
Open Access Status
Volume 25
Issue 6
Start page 1586
End page 1594
Total pages 9
Editor Donald G. Phinney
Miodrag Stojković
Place of publication Durham, NC, U.S.A.
Publisher Wiley-Blackwell and AlphaMed Press
Language eng
Subject 111401 Foetal Development and Medicine
111402 Obstetrics and Gynaecology
1114 Paediatrics and Reproductive Medicine
Abstract Murine mesenchymal stem cells are capable of differentiation into multiple cell types both in vitro and in vivo and may be good candidates to use as cell therapy for diseased or damaged organs. We have previously reported a method of enriching a population of murine MSCs that demonstrated a diverse differentiation potential both in vitro and in vivo. In this study, we show that this enriched population of murine mesenchymal stem cells embolize within lung capillaries following systemic injection and then rapidly expand within, and invade into, the lung parenchyma, forming tumor nodules. These lesions rarely contain cells bearing the immunohistochemical characteristics of lung epithelium, but they do show the characteristics of immature bone and cartilage that resembles exuberant fracture callus or well-differentiated. osteosarcoma. Our findings indicate that murine mesenchymal stem cells can behave in a manner similar to tumor cells, with dysregulated growth and aberrant differentiation within the alveolar microenvironment after four passages. We demonstrate that unlike human MSCs, MSCs from different mouse strains can acquire chromosomal abnormalities after only a few in vitro passages. Moreover, other parameters, such as mouse strain used, might also play a role in the induction of these tumors. These findings might be clinically relevant for future stem cell therapy studies.
Formatted abstract
Murine mesenchymal stem cells are capable of differentiation into multiple cell types both in vitro and in vivo and may be good candidates to use as cell therapy for diseased or damaged organs. We have previously reported a method of enriching a population of murine MSCs that demonstrated a diverse differentiation potential both in vitro and in vivo. In this study, we show that this enriched population of murine mesenchymal stem cells embolize within lung capillaries following systemic injection and then rapidly expand within, and invade into, the lung parenchyma, forming tumor nodules. These lesions rarely contain cells bearing the immunohistochemical characteristics of lung epithelium, but they do show the characteristics of immature bone and cartilage that resembles exuberant fracture callus or well-differentiated osteosarcoma. Our findings indicate that murine mesenchymal stem cells can behave in a manner similar to tumor cells, with dysregulated growth and aberrant differentiation within the alveolar microenvironment after four passages. We demonstrate that unlike human MSCs, MSCs from different mouse strains can acquire chromosomal abnormalities after only a few in vitro passages. Moreover, other parameters, such as mouse strain used, might also play a role in the induction of these tumors. These findings might be clinically relevant for future stem cell therapy studies. Disclosure of potential conflicts of interest is found at the end of this article.
Copyright © 2010 AlphaMed Press.

Keyword Tumor
Mesenchymal stem cell
Lung
Cell therapy
Osteosarcoma
Q-Index Code C1
Grant ID G0501781
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Sat, 21 Mar 2009, 02:18:04 EST by Mary-Anne Marrington on behalf of Faculty Of Health Sciences