Cai Yusheng, Ji Zhejun, Wang Si, Zhang Weiqi, Qu Jing, Belmonte Juan Carlos Izpisúa-, Liu Guang-Hui
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
Life Med. 2022 Nov 22;1(3):307-318. doi: 10.1093/lifemedi/lnac054. eCollection 2022 Dec.
Aging is a major risk factor for multiple diseases, including cardiovascular diseases, neurodegenerative disorders, osteoarthritis, and cancer. It is accompanied by the dysregulation of stem cells and other differentiated cells, and the impairment of their microenvironment. Cell therapies to replenish the abovementioned cells provide a promising approach to restore tissue homeostasis and alleviate aging and aging-related chronic diseases. Importantly, by leveraging gene editing technologies, genetic enhancement, an enhanced strategy for cell therapy, can be developed to improve the safety and efficacy of transplanted therapeutic cells. In this review, we provide an overview and discussion of the current progress in the genetic enhancement field, including genetic modifications of mesenchymal stem cells, neural stem cells, hematopoietic stem cells, vascular cells, and T cells to target aging and aging-associated diseases. We also outline questions regarding safety and current limitations that need to be addressed for the continued development of genetic enhancement strategies for cell therapy to enable its further applications in clinical trials to combat aging-related diseases.
衰老是多种疾病的主要风险因素，包括心血管疾病、神经退行性疾病、骨关节炎和癌症。衰老伴随着干细胞和其他分化细胞的失调，以及它们微环境的损害。补充上述细胞的细胞疗法为恢复组织稳态、缓解衰老及与衰老相关的慢性疾病提供了一种有前景的方法。重要的是，通过利用基因编辑技术，可以开发出基因增强这一细胞治疗的强化策略，以提高移植治疗性细胞的安全性和有效性。在这篇综述中，我们概述并讨论了基因增强领域的当前进展，包括对间充质干细胞、神经干细胞、造血干细胞、血管细胞和T细胞进行基因改造以针对衰老及与衰老相关的疾病。我们还概述了有关安全性的问题以及细胞治疗基因增强策略持续发展所需解决的当前局限性，以使该策略能在临床试验中进一步应用于对抗与衰老相关的疾病。
