University of Bari A. Moro, Department of Biomedical Sciences and Human Oncology, Section of Clinical Oncology, Bari, Italy.
Expert Opin Biol Ther. 2013 Jun;13 Suppl 1:S23-34. doi: 10.1517/14712598.2013.796357. Epub 2013 May 24.
Based on their tumor tropism, mesenchymal stem cells (MSCs) have been proposed as carriers of cytotoxic molecules in pioneering strategies of anti-cancer gene therapy. Similar to solid tumors, MSCs, genetically modified to stably express the TNF-related apoptosis-inducing ligand (TRAIL), have been applied to counter-attack multiple myeloma (MM) in vitro and envisioned as a promising strategy for future anti-MM treatments.
Accumulating evidence based on the detection of genetic and functional abnormalities in MSCs from MM patients points to the supportive function of MSCs in both the development and progression of MM, driven by chronic interplays with malignant cells within the marrow milieu. In this review, we revisit the function of MSCs in the pathophysiology of MM and explore the pivotal mechanisms of their interaction with myeloma cells. We also discuss the therapeutic significance of novel strategies using TRAIL-engineered MSCs in this cancer model, dissecting their role as new tools for future treatments against MM.
A cytotherapy based on TRAIL-engineered MSCs against MM may be successfully combined with either conventional approaches of autologous stem cell transplantation or with novel anti-MM drugs. Intensive preclinical investigations are required to identify the best sources as well as modalities of MSC administration, thus defining the translational suitability of this strategy in the clinical setting.
基于其肿瘤趋向性，间充质干细胞（MSCs）已被提议作为细胞毒性分子的载体，用于癌症基因治疗的开创性策略。与实体瘤类似，经基因修饰以稳定表达肿瘤坏死因子相关凋亡诱导配体（TRAIL）的 MSCs 已被应用于体外对抗多发性骨髓瘤（MM），并被视为未来抗 MM 治疗的有前途策略。
基于对 MM 患者 MSCs 中遗传和功能异常的检测，越来越多的证据表明 MSCs 在 MM 的发展和进展中具有支持作用，这是由其与骨髓微环境中的恶性细胞之间的慢性相互作用驱动的。在这篇综述中，我们重新审视了 MSCs 在 MM 病理生理学中的功能，并探讨了它们与骨髓瘤细胞相互作用的关键机制。我们还讨论了使用 TRAIL 工程 MSC 的新型策略在这种癌症模型中的治疗意义，剖析了它们作为未来对抗 MM 治疗的新工具的作用。
基于 TRAIL 工程 MSC 的针对 MM 的细胞疗法可能与自体干细胞移植的常规方法或新型抗 MM 药物成功结合。需要进行密集的临床前研究，以确定最佳的 MSC 给药来源和方式，从而确定该策略在临床环境中的转化适用性。
