Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics
Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics
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DOI：
10.1080/17425247.2021.1960309
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发表时间：
2021-07
影响因子：
6.6
通讯作者：
Yukiya Takayama;K. Kusamori;M. Nishikawa
中科院分区：
文献类型：
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作者：
Yukiya Takayama;K. Kusamori;M. Nishikawa
摘要引言实体瘤的药物递送仍然是一个重大的治疗挑战。间充质干/基质细胞（MSC）归巢于肿瘤组织，并可用作肿瘤靶向药物/基因递送载体。据报道，在临床前研究中，治疗性基因或抗癌药物负载的MSC显示出显著的抗肿瘤作用，并且已经注册了一些用于评估癌症患者中治疗性MSC的临床试验。在本综述中，我们首先讨论了MSC的来源和供体间异质性，它们的肿瘤归巢机制，以及MSC在基于MSC的癌症治疗中的给药途径。然后，我们总结了骨髓间充质干细胞作为治疗基因或抗癌药物的药物载体的治疗应用和载药骨髓间充质干细胞向癌细胞的药物递送机制。专家观点尽管许多临床前研究显示了显著的抗肿瘤作用，但评估基于MSC的癌症基因治疗的几项临床试验未能证明确证性结果，证明了有限的治疗效果。值得注意的是，基于MSC的癌症治疗的成功临床结果将需要解决所施用MSC的供体间异质性，同时沿着改善的肿瘤归巢效率和优化的从MSC到癌细胞的药物递送效率。
ABSTRACT Introduction Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehicles. Reportedly, therapeutic gene- or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered. Areas covered In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. We then summarize the therapeutic applications of MSCs as a drug delivery vehicle for therapeutic genes or anti-cancer drugs and the drug delivery mechanism from drug-loaded MSCs to cancer cells. Expert opinion Although numerous preclinical studies have revealed significant anti-tumor effects, several clinical trials assessing MSC-based cancer gene therapy have failed to demonstrate corroborative results, documenting limited therapeutic effects. Notably, a successful clinical outcome with MSC-based cancer therapy would require the interdonor heterogeneity of administered MSCs to be resolved, along with improved tumor-homing efficiency and optimized drug delivery efficiency from MSCs to cancer cells.