Golinelli Giulia, Mastrolia Ilenia, Aramini Beatrice, Masciale Valentina, Pinelli Massimo, Pacchioni Lucrezia, Casari Giulia, Dall'Ora Massimiliano, Soares Milena Botelho Pereira, Damasceno Patrícia Kauanna Fonseca, Silva Daniela Nascimento, Dominici Massimo, Grisendi Giulia
Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.
Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.
Front Pharmacol. 2020 Sep 29;11:529921. doi: 10.3389/fphar.2020.529921. eCollection 2020.
Since mesenchymal stromal/stem cells (MSCs) were discovered, researchers have been drawn to study their peculiar biological features, including their immune privileged status and their capacity to selectively migrate into inflammatory areas, including tumors. These properties make MSCs promising cellular vehicles for the delivery of therapeutic molecules in the clinical setting. In recent decades, the engineering of MSCs into biological vehicles carrying anticancer compounds has been achieved in different ways, including the loading of MSCs with chemotherapeutics or drug functionalized nanoparticles (NPs), genetic modifications to force the production of anticancer proteins, and the use of oncolytic viruses. Recently, it has been demonstrated that wild-type and engineered MSCs can release extracellular vesicles (EVs) that contain therapeutic agents. Despite the enthusiasm for MSCs as cyto-pharmaceutical agents, many challenges, including controlling the fate of MSCs after administration, must still be considered. Preclinical results demonstrated that MSCs accumulate in lung, liver, and spleen, which could prevent their engraftment into tumor sites. For this reason, physical, physiological, and biological methods have been implemented to increase MSC concentration in the target tumors. Currently, there are more than 900 registered clinical trials using MSCs. Only a small fraction of these are investigating MSC-based therapies for cancer, but the number of these clinical trials is expected to increase as technology and our understanding of MSCs improve. This review will summarize MSC-based antitumor therapies to generate an increasing awareness of their potential and limits to accelerate their clinical translation.
自从间充质基质/干细胞（MSCs）被发现以来，研究人员一直热衷于研究其独特的生物学特性，包括其免疫特权地位以及选择性迁移至包括肿瘤在内的炎症区域的能力。这些特性使MSCs成为临床环境中递送治疗分子的有前景的细胞载体。近几十年来，已通过不同方式将MSCs工程化为携带抗癌化合物的生物载体，包括用化疗药物或药物功能化纳米颗粒（NPs）加载MSCs、进行基因改造以促使抗癌蛋白的产生以及使用溶瘤病毒。最近，已证明野生型和工程化的MSCs可以释放含有治疗剂的细胞外囊泡（EVs）。尽管对MSCs作为细胞药物制剂充满热情，但仍必须考虑许多挑战，包括给药后控制MSCs的命运。临床前结果表明，MSCs在肺、肝和脾中蓄积，这可能会阻止它们植入肿瘤部位。因此，已采用物理、生理和生物学方法来提高靶肿瘤中MSCs的浓度。目前，有超过900项使用MSCs的注册临床试验。其中只有一小部分在研究基于MSCs的癌症治疗方法，但随着技术的进步以及我们对MSCs理解的加深，这些临床试验的数量预计将会增加。本综述将总结基于MSCs的抗肿瘤疗法，以提高人们对其潜力和局限性的认识，从而加速其临床转化。
