《生命科学》 2026, 38(6): 1152-1164

基于遗传增强间充质干细胞的衰老干预新策

雷敬辉¹ , 刘光慧^2,3,4,* , 王 思^1,*

¹首都医科大学宣武医院人脑保护高精尖创新中心，北京 100053 ²中国科学院动物研究所器官再生与智造全国重点实验室，北京 100101 ³北京干细胞与再生医学研究院，北京 100101 ⁴中国科学院大学，北 京 100049

摘　要：

衰老伴随成体干细胞功能衰退，是多种衰老相关疾病发生发展的核心因素。间充质干细胞因具备多向分化潜能、免疫调节能力及低免疫原性等优势，被视为延缓衰老、促进再生最具前景的细胞移植材料。然而，移植后的细胞在衰老机体恶劣微环境中存活率低、驻留时间短，严重制约了其疗效。为解决这一瓶颈，遗传增强策略应运而生，即通过基因编辑手段增强细胞的归巢能力、抵抗环境压力的能力及旁分泌功能，使其在衰老及相关疾病治疗中展现出优于野生型细胞的潜力。尽管长期安全性仍需进一步评估，但遗传增强间充质干细胞为开发新一代延缓衰老疗法指明了方向。

通讯作者：刘光慧 , Email:ghliu@ioz.ac.cn 王 思 , Email:wangsi@xwh.ccmu.edu.cn

Genetically enhanced mesenchymal stem cells for aging intervention

LEI Jing-Hui¹ , LIU Guang-Hui^2,3,4,* , WANG Si^1,*

¹Advanced Innovation Center for Human Brain Protection, Xuanwu Hospital Capital Medical University, Beijing 100053, China ²State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China ³Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China ⁴University of Chinese Academy of Sciences, Beijing 100049, China

Abstract:

Aging is an inevitable physiological process accompanied by a gradual decline in the function of adult stem cells, which is widely recognized as a core factor of various aging-related diseases, including cardiovascular diseases, diabetes, neurodegenerative diseases and osteoporosis. Mesenchymal stem cells (MSCs), due to their advantages such as multilineage differentiation potential, immunomodulatory capacity, and low immunogenicity, are considered the most promising cell transplantation materials for delaying aging and promoting regeneration. However, after transplantation, MSCs often face extremely low survival rates and short retention times in the harsh microenvironment of the aging body, which is characterized by oxidative stress, chronic inflammation, accumulation of toxic metabolites and reduced nutrient supply, severely limiting their therapeutic efficacy in clinical applications. To address this critical bottleneck, genetic enhancement strategies have emerged as a promising solution, which employ precise gene editing technologies such as CRISPR-Cas9 to modify target genes, thereby improving the homing ability of MSCs to damaged tissues, enhancing their resistance to adverse microenvironmental stress, and promoting their paracrine secretion of beneficial cytokines. These genetically enhanced MSCs show markedly superior therapeutic efficacy relative to wild-type MSCs in the treatment of aging and related diseases. Although the long-term safety and potential risks of genetically enhanced MSCs still require further evaluation through largesample, long-term preclinical and clinical studies, they undoubtedly represent an important breakthrough direction for the development of next-generation safe and effective anti-aging therapies.

Communication Author：LIU Guang-Hui , Email:ghliu@ioz.ac.cn WANG Si , Email:wangsi@xwh.ccmu.edu.cn