Malinovskaya Elena M, Veiko Natalia N, Ershova Elisaveta S, Kameneva Larisa V, Konkova Marina S, Kostyuk Svetlana V
Laboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), 115522 Moscow, Russia.
Institute of Medicine, Department of Biology and General Genetics, Russian Peoples' Friendship University Named After Patrice Lumumba, 117198 Moscow, Russia.
Front Biosci (Landmark Ed). 2025 Mar 31;30(4):28255. doi: 10.31083/FBL28255.
Acute myocardial infarction (AMI) is accompanied by damage to heart tissues and some cell death. Stem cells are localized in the affected area and contribute to tissue repair. Studies have previously shown that the concentration of cell-free DNA (cfDNA) in the blood (ami-cfDNA) increases significantly in patients with AMI, and GC-rich and oxidized DNA fragments accumulate in the composition of ami-cfDNA. As a result, ami-cfDNA exhibits biological activity in vitro against various types of differentiated human cells. Potentially, ami-cfDNA can influence the functional activity and direction of stem cell differentiation. To verify this assumption, we investigated the effect of ami-cfDNA fragments isolated from the blood of patients with AMI on human adipose tissue mesenchymal stem cells (MSCs) .
The MSC line was used and characterized by stem cell surface markers. Ami-cfDNA and control (hc-cfDNA) samples were isolated from the blood plasma of seven AMI patients and ten healthy donors. The early (0.5-3 hours) and late (1-3 weeks) responses of MSCs to cfDNA action were analyzed. The level of reactive oxygen species, the expression level of numerous genes (, , , , , , , , , , , , , ), the level of double-stranded DNA breaks in nuclei, and changes in the spatial organization of the chromatin in the nucleus were determined using the quantitative (real-time) polymerase chain reaction (qPCR), flow cytometry, fluorescence microscopy, fluorescent hybridization (FISH) assays.
Introducing ami-cfDNA fragments into the cell culture medium stimulates rapid and transient induction of oxidative stress in MSCs (early response). Oxidative stress stimulates the spatial reorganization of chromatin to develop an adaptive response (AR). The adaptive response includes an antioxidant and anti-apoptotic response and activation of repair genes. The ami-cfDNA fragments, unlike hc-cfDNA, stimulate the myogenic differentiation of MSCs under prolonged exposure (late response).
The ami-cfDNA increases the survival of MSCs in the model system by inducing a pronounced adaptive cellular response. Prolonged exposure to ami-cfDNA provokes myogenic differentiation of MSCs. Under acute stress conditions caused by AMI in the body, ami-cfDNA may positively affect the restoration of damaged heart muscle.
急性心肌梗死（AMI）伴有心脏组织损伤和一些细胞死亡。干细胞定位于受影响区域并有助于组织修复。先前的研究表明，AMI患者血液中无细胞DNA（cfDNA，即ami-cfDNA）的浓度显著增加，并且富含鸟嘌呤和胞嘧啶的氧化DNA片段在ami-cfDNA的组成中积累。因此，ami-cfDNA在体外对各种类型的分化人细胞具有生物活性。潜在地，ami-cfDNA可以影响干细胞分化的功能活性和方向。为了验证这一假设，我们研究了从AMI患者血液中分离的ami-cfDNA片段对人脂肪组织间充质干细胞（MSCs）的影响。
使用MSC系并通过干细胞表面标志物进行表征。从7例AMI患者和10例健康供体的血浆中分离出ami-cfDNA和对照（hc-cfDNA）样本。分析了MSCs对cfDNA作用的早期（0.5 - 3小时）和晚期（1 - 3周）反应。使用定量（实时）聚合酶链反应（qPCR）、流式细胞术、荧光显微镜、荧光原位杂交（FISH）测定法测定活性氧水平、众多基因（、、、、、、、、、、、、、）的表达水平、细胞核中双链DNA断裂水平以及细胞核中染色质空间组织的变化。
将ami-cfDNA片段引入细胞培养基中会刺激MSCs中氧化应激的快速和短暂诱导（早期反应）。氧化应激刺激染色质的空间重组以产生适应性反应（AR）。适应性反应包括抗氧化和抗凋亡反应以及修复基因的激活。与hc-cfDNA不同，ami-cfDNA片段在长时间暴露下（晚期反应）会刺激MSCs的成肌分化。
ami-cfDNA通过诱导明显的适应性细胞反应增加了模型系统中MSCs 的存活率。长时间暴露于ami-cfDNA会引发MSCs的成肌分化。在体内由AMI引起的急性应激条件下，ami-cfDNA可能对受损心肌的恢复产生积极影响。
需注意，原文中部分基因名称未完整给出，用“、”代替，翻译时保留了这种情况。
