Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
Department of Molecular and Radiation Oncology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Stem Cell Rev Rep. 2019 Jun;15(3):356-373. doi: 10.1007/s12015-019-09886-3.
Chemotherapy constitutes one of the key treatment modalities for solid and hematological malignancies. Albeit being an effective treatment, chemotherapy application is often limited by its damage to healthy tissues, and curative treatment options for chemotherapy-related side effects are largely missing. As mesenchymal stromal cells (MSCs) are known to exhibit regenerative capacity mainly by supporting a beneficial microenvironment for tissue repair, MSC-based therapies may attenuate chemotherapy-induced tissue injuries. An increasing number of animal studies shows favorable effects of MSC-based treatments; however, clinical trials for MSC therapies in the context of chemotherapy-related side effects are rare. In this concise review, we summarize the current knowledge of the effects of MSCs on chemotherapy-induced tissue toxicities. Both preclinical and early clinical trials investigating MSC-based treatments for chemotherapy-related side reactions are presented, and mechanistic explanations about the regenerative effects of MSCs in the context of chemotherapy-induced tissue damage are discussed. Furthermore, challenges of MSC-based treatments are outlined that need closer investigations before these multipotent cells can be safely applied to cancer patients. As any pro-tumorigenicity of MSCs needs to be ruled out prior to clinical utilization of these cells for cancer patients, the pro- and anti-tumorigenic activities of MSCs are discussed in detail.
化疗是治疗实体瘤和血液系统恶性肿瘤的主要方法之一。虽然化疗是一种有效的治疗方法,但由于其对健康组织的损伤,其应用常常受到限制,且针对化疗相关副作用的治疗选择也基本缺失。间充质基质细胞(MSCs)因其能够通过支持有利于组织修复的微环境来发挥再生能力而备受关注,基于 MSC 的治疗方法可能会减轻化疗引起的组织损伤。越来越多的动物研究表明 MSC 治疗具有良好的效果;然而,针对化疗相关副作用的 MSC 治疗的临床试验却很少。在这篇简明的综述中,我们总结了 MSCs 对化疗引起的组织毒性的作用的现有知识。我们介绍了针对化疗相关不良反应的基于 MSC 的治疗的临床前和早期临床试验,并讨论了 MSCs 在化疗引起的组织损伤背景下的再生作用的机制解释。此外,还概述了基于 MSC 的治疗方法所面临的挑战,在这些多能细胞能够安全地应用于癌症患者之前,需要对这些挑战进行更密切的研究。由于在将这些细胞用于癌症患者之前需要排除 MSCs 的任何促瘤性,因此详细讨论了 MSCs 的促瘤和抑瘤活性。