释放紫杉醇的间充质基质细胞在动态三维培养系统中抑制多发性骨髓瘤细胞的生长。
Paclitaxel-releasing mesenchymal stromal cells inhibit the growth of multiple myeloma cells in a dynamic 3D culture system.
作者信息
Bonomi Arianna, Steimberg Nathalie, Benetti Anna, Berenzi Angiola, Alessandri Giulio, Pascucci Luisa, Boniotti Jennifer, Coccè Valentina, Sordi Valeria, Pessina Augusto, Mazzoleni Giovanna
机构信息
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia, Brescia, Italy.
出版信息
Hematol Oncol. 2017 Dec;35(4):693-702. doi: 10.1002/hon.2306. Epub 2016 Jun 10.
Multiple myeloma is an aggressive tumour able to suppress osteoblastogenesis probably mediated by bone marrow mesenchymal stromal cells (BM-MSCs) that can also support plasma cell growth/survival. The use of MSCs for multiple myeloma therapy is a controversial topic because of the contradictory results on the capacity of MSCs to inhibit or to promote cancer growth. Our previous studies demonstrated that MSCs could be loaded with Paclitaxel (PTX) and used to deliver the drug in situ in amount affecting tumour growth (in vitro and in vivo). Therefore, independently on the discussed action of MSCs in myeloma, MSCs could represent a 'trojan horse' to vehicle and deliver anti-tumour agents into bone marrow. This study confirms, by an in vitro 3D dynamic culture system, that PTX loaded BM-MSCs (PTXr-MSCs) are active on the proliferation of RPMI 8226, a human myeloma cell line. Our results demonstrated a dramatic suppression of myeloma cell growth by PTXr-MSCs, suggesting that drug loaded MSCs could be a tool to deliver drug into the bone marrow. Drug releasing MSCs provide a therapeutic approach to potentiate the existing treatments against a very aggressive malignancy as multiple myeloma. Copyright © 2016 John Wiley & Sons, Ltd.
多发性骨髓瘤是一种侵袭性肿瘤,可能通过骨髓间充质基质细胞(BM-MSCs)介导抑制成骨细胞生成,而骨髓间充质基质细胞也能支持浆细胞的生长/存活。由于骨髓间充质干细胞抑制或促进癌症生长的能力存在矛盾结果,因此将其用于多发性骨髓瘤治疗是一个有争议的话题。我们之前的研究表明,骨髓间充质干细胞可以负载紫杉醇(PTX),并用于原位递送药物,其剂量会影响肿瘤生长(体外和体内)。因此,无论骨髓间充质干细胞在骨髓瘤中所讨论的作用如何,它们都可能代表一种“特洛伊木马”,用于运载并将抗肿瘤药物递送至骨髓。本研究通过体外三维动态培养系统证实,负载紫杉醇的骨髓间充质干细胞(PTXr-MSCs)对人骨髓瘤细胞系RPMI 8226的增殖有活性作用。我们的结果表明,PTXr-MSCs对骨髓瘤细胞生长有显著抑制作用,这表明负载药物的骨髓间充质干细胞可能是一种将药物递送至骨髓的工具。释放药物的骨髓间充质干细胞为增强针对多发性骨髓瘤这种极具侵袭性的恶性肿瘤的现有治疗方法提供了一种治疗途径。版权所有© 2016约翰威立父子有限公司。