Astellas Institute for Regenerative Medicine, Westborough, MA, USA.
Nat Rev Drug Discov. 2020 Jul;19(7):463-479. doi: 10.1038/s41573-020-0064-x. Epub 2020 Apr 6.
Naturally occurring stem cells isolated from humans have been used therapeutically for decades. This has primarily involved the transplantation of primary cells such as haematopoietic and mesenchymal stem cells and, more recently, derivatives of pluripotent stem cells. However, the advent of cell-engineering approaches is ushering in a new generation of stem cell-based therapies, greatly expanding their therapeutic utility. These next-generation stem cells are being used as 'Trojan horses' to improve the delivery of drugs and oncolytic viruses to intractable tumours and are also being engineered with angiogenic, neurotrophic and anti-inflammatory molecules to accelerate the repair of injured or diseased tissues. Moreover, gene therapy and gene editing technologies are being used to create stem cell derivatives with improved functionality, specificity and responsiveness compared with their natural counterparts. Here, we review these engineering approaches and areas in which they will help broaden the utility and clinical applicability of stem cells.
几十年来,从人体中分离出来的天然存在的干细胞已被用于治疗。这主要涉及到原代细胞的移植,如造血干细胞和间充质干细胞,以及最近的多能干细胞衍生物。然而,细胞工程方法的出现正在迎来新一代基于干细胞的治疗方法,极大地扩展了它们的治疗用途。这些下一代干细胞被用作“特洛伊木马”,以提高药物和溶瘤病毒在难治性肿瘤中的传递效率,并且还被设计成具有血管生成、神经营养和抗炎分子,以加速受损或患病组织的修复。此外,基因治疗和基因编辑技术正被用于创造具有改善的功能、特异性和反应性的干细胞衍生物,与天然的干细胞相比。在这里,我们回顾了这些工程方法,以及它们将如何帮助扩大干细胞的效用和临床适用性的领域。