Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status
2015
Avril, Pierre | Le Nail, Louis-Romée | Brennan, Meadhbh, A | Rosset, Philippe | de Pinieux, Gonzague | Layrolle, Pierre | Heymann, Dominique | Perrot, Pierre | Trichet, Valérie | Physiopathologie des Adaptations Nutritionnelles (PhAN) ; Institut National de la Recherche Agronomique (INRA)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN) | Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) | CHU Trousseau [APHP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | Service de Chirurgie Plastique et des Brulés [CHU Nantes] ; Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) | This work was supported by INSERM, the “Ligue Contre le Cancer” (Equipe Labellisée LIGUE 2012; grant EL2012NCC/DH), the “Fédération Nationale Enfants et Santé” and the “Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent(“appel à projet 2013”).
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Показать больше [+] Меньше [-]Английский. 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.
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