Early and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial Infarction
Background: 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 (a...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2025-03-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/30/4/10.31083/FBL28255 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850142833962385408 |
|---|---|
| author | Elena M. Malinovskaya Natalia N. Veiko Elisaveta S. Ershova Larisa V. Kameneva Marina S. Konkova Svetlana V. Kostyuk |
| author_facet | Elena M. Malinovskaya Natalia N. Veiko Elisaveta S. Ershova Larisa V. Kameneva Marina S. Konkova Svetlana V. Kostyuk |
| author_sort | Elena M. Malinovskaya |
| collection | DOAJ |
| description | Background: 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) in vitro. Materials and Methods: 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 (NOX4, NRF2, BRCA1, BCL2, BAX, MYOD1, MYOG, MYF5, MRF4, RUNX2, SPP1, OCN, LPL, AP2), 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 in situ hybridization (FISH) assays. Results: 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). Conclusions: 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. |
| format | Article |
| id | doaj-art-74e4769cd6414801b7fd15c1788b404d |
| institution | OA Journals |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-74e4769cd6414801b7fd15c1788b404d2025-08-20T02:28:55ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-03-013042825510.31083/FBL28255S2768-6701(25)01679-XEarly and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial InfarctionElena M. Malinovskaya0Natalia N. Veiko1Elisaveta S. Ershova2Larisa V. Kameneva3Marina S. Konkova4Svetlana V. Kostyuk5Laboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), 115522 Moscow, RussiaLaboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), 115522 Moscow, RussiaLaboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), 115522 Moscow, RussiaLaboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), 115522 Moscow, RussiaLaboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), 115522 Moscow, RussiaLaboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), 115522 Moscow, RussiaBackground: 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) in vitro. Materials and Methods: 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 (NOX4, NRF2, BRCA1, BCL2, BAX, MYOD1, MYOG, MYF5, MRF4, RUNX2, SPP1, OCN, LPL, AP2), 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 in situ hybridization (FISH) assays. Results: 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). Conclusions: 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.https://www.imrpress.com/journal/FBL/30/4/10.31083/FBL28255acute myocardial infarctioncell-free dnahuman mesenchymal stem cells (mscs) |
| spellingShingle | Elena M. Malinovskaya Natalia N. Veiko Elisaveta S. Ershova Larisa V. Kameneva Marina S. Konkova Svetlana V. Kostyuk Early and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial Infarction Frontiers in Bioscience-Landmark acute myocardial infarction cell-free dna human mesenchymal stem cells (mscs) |
| title | Early and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial Infarction |
| title_full | Early and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial Infarction |
| title_fullStr | Early and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial Infarction |
| title_full_unstemmed | Early and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial Infarction |
| title_short | Early and Late Responses of Cultured Human Mesenchymal Stem Cells (MSCs) to Cell-free DNA (cfDNA) in Patients With Acute Myocardial Infarction |
| title_sort | early and late responses of cultured human mesenchymal stem cells mscs to cell free dna cfdna in patients with acute myocardial infarction |
| topic | acute myocardial infarction cell-free dna human mesenchymal stem cells (mscs) |
| url | https://www.imrpress.com/journal/FBL/30/4/10.31083/FBL28255 |
| work_keys_str_mv | AT elenammalinovskaya earlyandlateresponsesofculturedhumanmesenchymalstemcellsmscstocellfreednacfdnainpatientswithacutemyocardialinfarction AT natalianveiko earlyandlateresponsesofculturedhumanmesenchymalstemcellsmscstocellfreednacfdnainpatientswithacutemyocardialinfarction AT elisavetasershova earlyandlateresponsesofculturedhumanmesenchymalstemcellsmscstocellfreednacfdnainpatientswithacutemyocardialinfarction AT larisavkameneva earlyandlateresponsesofculturedhumanmesenchymalstemcellsmscstocellfreednacfdnainpatientswithacutemyocardialinfarction AT marinaskonkova earlyandlateresponsesofculturedhumanmesenchymalstemcellsmscstocellfreednacfdnainpatientswithacutemyocardialinfarction AT svetlanavkostyuk earlyandlateresponsesofculturedhumanmesenchymalstemcellsmscstocellfreednacfdnainpatientswithacutemyocardialinfarction |