Katakowski Mark, Chopp Michael
Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
Department of Physics, Oakland University, Rochester, MI, USA.
Cell Mol Neurobiol. 2016 Apr;36(3):343-52. doi: 10.1007/s10571-015-0280-9. Epub 2016 Mar 17.
Exosomes are small microvesicles released by cells that efficiently transfer their molecular cargo to other cells, including tumor. Exosomes may pass the blood-brain barrier and have been demonstrated to deliver RNAs contained within to brain. As they are non-viable, the risk profile of exosomes is thought to be less than that of cellular therapies. Exosomes can be manufactured at scale in culture, and exosomes can be engineered to incorporate therapeutic miRNAs, siRNAs, or chemotherapeutic molecules. As natural biological delivery vehicles, interest in the use of exosomes as therapeutic delivery agents is growing. We previously demonstrated a novel treatment whereby mesenchymal stromal cells were employed to package tumor-suppressing miR-146b into exosomes, which were then used to reduce malignant glioma growth in rat. The use of exosomes to raise the immune system against tumor is also drawing interest. Exosomes from dendritic cells which are antigen-presenting, and have been used for treatment of brain tumor may be divided into three categories: (1) exosomes for immunomodulation-based therapy, (2) exosomes as delivery vehicles for anti-tumor nucleotides, and (3) exosomes as drug delivery vehicles. Here, we will provide an overview of these three applications of exosomes to treat brain tumor, and examine their prospects on the long road to clinical use.
外泌体是细胞释放的微小囊泡,能有效地将其分子货物转移到其他细胞,包括肿瘤细胞。外泌体可以穿过血脑屏障,并已被证明能将其中包含的RNA传递到大脑。由于它们不具有活性,外泌体的风险状况被认为低于细胞疗法。外泌体可以在培养中大规模生产,并且可以进行工程改造以掺入治疗性miRNA、siRNA或化疗分子。作为天然的生物递送载体,将外泌体用作治疗递送剂的兴趣正在增加。我们之前展示了一种新的治疗方法,即利用间充质基质细胞将肿瘤抑制性miR-146b包装到外泌体中,然后用于减少大鼠恶性胶质瘤的生长。利用外泌体增强免疫系统对抗肿瘤也引起了人们的兴趣。来自树突状细胞的外泌体具有抗原呈递作用,已被用于治疗脑肿瘤,可分为三类:(1)基于免疫调节疗法的外泌体,(2)作为抗肿瘤核苷酸递送载体的外泌体,以及(3)作为药物递送载体的外泌体。在此,我们将概述外泌体治疗脑肿瘤的这三种应用,并探讨它们在通往临床应用的漫长道路上的前景。