Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status

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• 作者：Pierre Avril^a ; ^b ; Louis-Romé ; e Le Nail^a ; ^b ; ^c ; ^d ; Meadhbh Á ; . Brennan^a ; ^b ; Philippe Rosset^a ; ^b ; ^c ; ^d ; Gonzague De Pinieux^a ; ^b ; ^d ; ^f ; Pierre Layrolle^a ; ^b ; Dominique Heymann^a ; ^b ; Pierre Perrot^a ; ^b ; ^e ; Valé ; rie Trichet^a ; ^b ; ^{valerie.trichet@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Mesenchymal stem cell ; Osteosarcoma ; Adipose tissue transfer ; Cell cycle ; Quiescence
• 刊名：Journal of Bone Oncology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：5
• 期：1
• 页码：5-14
• 全文大小：6403 K

文摘

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.