title: Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status.
abstract: Conventional therapy of primary bone tumors includes surgical excision with wide resection, which leads to physical and aesthetic defects. For reconstruction of bone and joints, allografts can be supplemented with mesenchymal stem cells (MSCs). Similarly, adipose tissue transfer (ATT) is supplemented with adipose-derived stem cells (ADSCs) to improve the efficient grafting in the correction of soft tissue defects. MSC-like cells may also be used in tumor-targeted cell therapy. However, MSC may have adverse effects on sarcoma development. In the present study, human ADSCs, MSCs and pre-osteoclasts were co-injected with human MNNG-HOS osteosarcoma cells in immunodeficient mice. ADSCs and MSCs, but not the osteoclast precursors, accelerated the local proliferation of MNNG-HOS osteosarcoma cells. However, the osteolysis and the metastasis process were not exacerbated by ADSCs, MSCs, or pre-osteoclasts. In vitro proliferation of MNNG-HOS and Saos-2 osteosarcoma cells was increased up to 2-fold in the presence of ADSC-conditioned medium. In contrast, ADSC-conditioned medium did not change the dormant, quiescent state of osteosarcoma cells cultured in oncospheres. Due to the enhancing effect of ADSCs/MSCs on in vivo/in vitro proliferation of osteosarcoma cells, MSCs may not be good candidates for osteosarcoma-targeted cell therapy. Although conditioned medium of ADSCs accelerated the cell cycle of proliferating osteosarcoma cells, it did not change the quiescent state of dormant osteosarcoma cells, indicating that ADSC-secreted factors may not be involved in the risk of local recurrence.
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Avril
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France; University Hospital, Service de Chirurgie Orthopédique et Traumatologique, Tours F-37044, France; Faculté de Médecine, Université François Rabelais, Tours F-37044, France.
authors.forename: Louis-Romée
authors.initials: LR
authors.lastname: Le Nail
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Meadhbh Á
authors.initials: MÁ
authors.lastname: Brennan
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France; University Hospital, Service de Chirurgie Orthopédique et Traumatologique, Tours F-37044, France; Faculté de Médecine, Université François Rabelais, Tours F-37044, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rosset
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France; Faculté de Médecine, Université François Rabelais, Tours F-37044, France; University Hospital, Service d'Anatomie Pathologique, Tours F-37044, France.
authors.forename: Gonzague
authors.initials: G
authors.lastname: De Pinieux
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Layrolle
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France; University Hospital, Service de Chirurgie Plastique et des Brûlés, Nantes F-44093, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Perrot
authors.affiliation: INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Trichet
keywords: Adipose tissue transfer; Cell cycle; Mesenchymal stem cell; Osteosarcoma; Quiescence