University of Essex, School of Biological Sciences, Cancer and Stem Cell Biology Group, Wivenhoe Park, CO4 3SQ, Colchester, United Kingdom.
Cancer Lett. 2018 Feb 1;414:239-249. doi: 10.1016/j.canlet.2017.11.025. Epub 2017 Nov 24.
Mesenchymal stem cells (MSCs) are multipotent stromal cells which can differentiate into a variety of cell types including osteoblasts, adipocytes and chondrocytes. They are normally resident in adipose tissue, bone marrow and the umbilical cord, but can also be found in other tissues and are known to be recruited to sites of wound healing as well as growing tumours. The therapeutic potential of MSCs has been explored in a number of phase I/II and III clinical trials, of which several were targeted against graft-versus-host disease and to support engraftment of haematopoietic stem cells (HSCs), but currently only very few in the oncology field. There are now three clinical trials either ongoing or recruiting patients that use MSCs to treat tumour disease. In these, MSCs target gastrointestinal, lung and ovarian cancer, respectively. The first study uses MSCs loaded with a HSV-TK expression construct under the control of the CCL5 promoter, and has recently reported successful completion of Phase I/II. While no adverse side effects were seen during this study, no outcomes with respect to therapeutic benefits have been published. The other clinical trials targeting lung and ovarian cancer will be using MSCs expressing cytokines as therapeutic payload. Despite these encouraging early steps towards their clinical use, many questions are still unanswered regarding the biology of MSCs in normal and pathophysiological settings. In this review, in addition to summarising the current state of MSC-based therapeutic approaches for cancer, we will describe the remaining questions, obstacles and risks, as well as novel developments such as MSC-derived nanoghosts.
间充质干细胞（MSCs）是多能基质细胞，可分化为多种细胞类型，包括成骨细胞、脂肪细胞和软骨细胞。它们通常存在于脂肪组织、骨髓和脐带中，但也可以在其他组织中找到，并被招募到伤口愈合和生长肿瘤的部位。MSCs 的治疗潜力已在许多 I/II 期和 III 期临床试验中进行了探索，其中一些针对移植物抗宿主病，并支持造血干细胞（HSCs）的植入，但目前仅在肿瘤学领域非常有限。现在有三项临床试验正在进行或招募患者，使用 MSCs 治疗肿瘤疾病。在这些试验中，MSCs 分别针对胃肠道、肺部和卵巢癌。第一项研究使用 MSC 负载 HSV-TK 表达构建体，该构建体受 CCL5 启动子的控制，并已最近报告完成了 I/II 期。虽然在这项研究中没有观察到不良反应，但尚未公布关于治疗效果的结果。针对肺癌和卵巢癌的其他临床试验将使用表达细胞因子的 MSC 作为治疗有效载荷。尽管在将其用于临床方面取得了这些令人鼓舞的早期进展，但关于 MSCs 在正常和病理生理环境中的生物学特性仍有许多问题尚未得到解答。在这篇综述中，除了总结基于 MSC 的癌症治疗方法的现状外，我们还将描述仍存在的问题、障碍和风险，以及 MSC 衍生的纳米幽灵等新的发展。
