Yang Song, Zhuang Weizhong, Zhou Lishi, Kong Weiwei, Zou Wanwan, Zhu Qikun, Bian Enze, Lin Bin, Cen Jianzheng, Gao Qiang, Chen Jimei
Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510030, China.
Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510030, China.
BMC Biotechnol. 2025 Jul 1;25(1):59. doi: 10.1186/s12896-025-00993-3.
Myocardial infarction, characterized by insufficient blood supply to the heart, leads to ischemia and hypoxia of myocardial tissues, causing injury and decreased cardiac function. Despite improvements in pharmaceutical and interventional therapies, it remains a leading cause of death worldwide. Human umbilical cord mesenchymal stem cells (hUC-MSCs) play an important role in the repair of infarcted myocardium by promoting angiogenesis, reducing inflammation, secreting growth factors and cytokines. However, the harsh hypoxic microenvironment of infarcted myocardial tissue poses a threat to the survival and function of transplanted hUC-MSCs. In this study, we modified the candidate gene promoter of hUC-MSCs under hypoxic conditions and created a promoter that can respond quickly under hypoxic conditions. We found that the modified promoter significantly promoted the transcription efficiency as hypoxia time increased. This indicates that the engineered hypoxia-response promoter can effectively drive gene expression in a hypoxic environment. Furthermore, the transcription efficiency of the modified promoter under normoxic conditions is lower than that of common promoters in eukaryotic organisms, suggesting that this effect can improve the efficacy and safety of hUC-MSC-based myocardial infarction treatment by ensuring that cells function effectively in the damaged hypoxic area.
心肌梗死的特征是心脏供血不足，导致心肌组织缺血缺氧，造成损伤并使心脏功能下降。尽管药物治疗和介入治疗有所改善，但它仍是全球主要的死亡原因。人脐带间充质干细胞（hUC-MSCs）通过促进血管生成、减轻炎症、分泌生长因子和细胞因子，在梗死心肌的修复中发挥重要作用。然而，梗死心肌组织恶劣的缺氧微环境对移植的hUC-MSCs的存活和功能构成威胁。在本研究中，我们在缺氧条件下对hUC-MSCs的候选基因启动子进行了修饰，创建了一个在缺氧条件下能快速响应的启动子。我们发现，随着缺氧时间的增加，修饰后的启动子显著提高了转录效率。这表明工程化的缺氧反应启动子能在缺氧环境中有效驱动基因表达。此外，修饰后的启动子在常氧条件下的转录效率低于真核生物中的普通启动子，这表明这种效应可以通过确保细胞在受损缺氧区域有效发挥功能，提高基于hUC-MSCs的心肌梗死治疗的疗效和安全性。
