Murine but not Human Mesenchymal Stem Cells Generate Osteosarcoma-Like Lesions in the Lung

¹ Centre for Respiratory Research, Rayne Institute, University College London, London, United Kingdom; Hematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom
² Experimental Pathology Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom; Department of Histopathology, Imperial College London, Hammersmith Campus, London, United Kingdom
³ Institute of Reproductive and Developmental Biology, Department of Paediatrics, Imperial College London, Hammersmith Campus, London, United Kingdom
⁴ Centre for Respiratory Research, Rayne Institute, University College London, London, United Kingdom
⁵ Hematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom

^* To whom correspondence should be addressed. E-mail: Dominique.Bonnet{at}cancer.org.uk.

	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 to enrich a population of murine mesenchymal stem cells which 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 epithelial but show 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 micro-environment after four passages. We demonstrate that unlike human mesenchymal stem cells (MSCs), MSCs from different mouse strains can acquire chromosomal abnormalities after only a few in vitro passages. Moreover other parameters like 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.