Enhanced human adipose-derived stem cells with VEGFA and bFGF mRNA promote stable vascular regeneration and improve cardiac function following myocardial infarction

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-02-26 DOI:10.1002/ctm2.70250

Kaixiang Li, Runjiao Luo, Xindi Yu, Wei Dong, Guoliang Hao, Dan Hu, Ziyou Yu, Minglu Liu, Tingting Lu, Xiangying Wang, Xin Tang, Xinjun Lin, Huijing Wang, Wei Wang, Wei Fu

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引用次数: 0

Abstract

Mesenchymal stem cell therapy involves the secretion of various factors to regulate the local microenvironment in various of diseases. This therapy offers hope for treating acute myocardial infarction (MI), which poses a serious threat to human health. However, challenges such as low paracrine efficiency and poor cell survival persist due to the harsh post-infarction conditions, such as hypoxia. Recently, enhanced cell therapy, in which vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) are used as therapeutic agents to limit myocardial injury and simultaneously induce neovascularisation, has been recognised as a promising new strategy to improve the efficacy of cell therapy. Chemically synthetic modified messenger RNA (modRNA), a novel protein expression technology, enables safe, rapid, efficient and pulsatile expression of target proteins in vivo and in vitro settings. It has been widely applied in the fields of vaccine research and tissue regeneration. In this study, human adipose-derived stem cells (hADSCs) were transfected with VEGFA and bFGF modRNA to transiently overexpress these proteins before transplantation. This modification enhanced the paracrine effect of transplanted hADSCs and promoted stability in the vascular network at the transplantation site. Overexpression of VEGFA and bFGF in hADSCs not only inhibited apoptosis but also reduced ventricular remodelling and improved cardiac function and left ventricular conduction. Overall, the additive effects of VEGFA modRNA, bFGF modRNA and hADSCs hold promise for comprehensive cardiac repair post-MI and show substantial potential for treating ischemic heart diseases.

Key points

ModRNAs-transfected hADSCs exhibit pulsed and transient expression, enabling efficient production of functional VEGFA and bFGF proteins.
Intracardiac injection of these engineered hADSCs leads to the enhancement of cardiac function and the improvement of electrical conduction.
The hADSCs^dual mainly exerts its effect on myocardial infarction by promoting stable vascular regeneration and suppressing cell apoptosis.

Abstract Image

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带有 VEGFA 和 bFGF mRNA 的增强型人脂肪来源干细胞可促进稳定的血管再生，并改善心肌梗死后的心脏功能

间充质干细胞治疗涉及多种因子的分泌来调节各种疾病的局部微环境。该疗法为治疗严重威胁人类健康的急性心肌梗死（MI）带来了希望。然而，由于梗死后缺氧等恶劣条件，诸如旁分泌效率低和细胞存活率差等挑战仍然存在。最近，利用血管内皮生长因子A （VEGFA）和碱性成纤维细胞生长因子（bFGF）作为治疗药物来限制心肌损伤并同时诱导新生血管的强化细胞治疗被认为是提高细胞治疗疗效的一种有前景的新策略。化学合成修饰信使RNA （modRNA）是一种新型的蛋白质表达技术，能够在体内和体外安全、快速、高效和脉动地表达靶蛋白。它已广泛应用于疫苗研究和组织再生领域。在这项研究中，人脂肪源性干细胞（hADSCs）在移植前转染VEGFA和bFGF modRNA，短暂过表达这些蛋白。这种修饰增强了移植hascs的旁分泌作用，促进了移植部位血管网络的稳定性。在hascs中过表达VEGFA和bFGF不仅可以抑制细胞凋亡，还可以减少心室重构，改善心功能和左心室传导。总的来说，VEGFA modRNA、bFGF modRNA和hscs的加性作用有望在心肌梗死后进行全面的心脏修复，并显示出治疗缺血性心脏病的巨大潜力。modrnas转染的hascs表现出脉冲和瞬时表达，能够有效地产生功能性VEGFA和bFGF蛋白。心内注射这些工程化的hascs可增强心功能和改善电传导。hads主要通过促进血管稳定再生和抑制细胞凋亡来发挥其对心肌梗死的作用。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.