Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies
Abstract Doxorubicin-induced cardiomyopathy (DOX-IC) is a significant and common complication in patients undergoing chemotherapy, leading to cardiac remodeling and reduced heart function. We hypothesized that the intrapericardial injection of hydrogels derived from the cardiac decellularized extrac...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-87939-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571642755153920 |
|---|---|
| author | Tácia Tavares Aquinas Liguori Gabriel Romero Liguori Viktor Sinkunas Cristiano Jesus Correia Raphael dos Santos Coutinho e Silva Fernando Luiz Zanoni Vera Demarchi Aiello Martin Conrad Harmsen Luiz Felipe Pinho Moreira |
| author_facet | Tácia Tavares Aquinas Liguori Gabriel Romero Liguori Viktor Sinkunas Cristiano Jesus Correia Raphael dos Santos Coutinho e Silva Fernando Luiz Zanoni Vera Demarchi Aiello Martin Conrad Harmsen Luiz Felipe Pinho Moreira |
| author_sort | Tácia Tavares Aquinas Liguori |
| collection | DOAJ |
| description | Abstract Doxorubicin-induced cardiomyopathy (DOX-IC) is a significant and common complication in patients undergoing chemotherapy, leading to cardiac remodeling and reduced heart function. We hypothesized that the intrapericardial injection of hydrogels derived from the cardiac decellularized extracellular matrix (dECM) loaded with adipose tissue-derived stromal cells (ASC) and their secretome dampens or reverses the progression of DOX-IC. DOX-IC was induced in Wistar male rats through ten weekly intra-peritoneal injections of doxorubicin (cumulative dose: 18 mg/kg). We performed intrapericardial treatment in week five with dECM hydrogel loaded with ASC and their conditioned medium (CMed). The volume of intrapericardial injection was 2 ml/kg, the ASC density was 20 million/mL, while the hydrogel contained 100-fold concentrated CMed. Interstitial myocardial fibrosis was assessed by PicroSirius Red staining and hemodynamics parameters in pressure-volume loops. Compared to saline controls, interstitial myocardial fibrosis was reduced in ASC/CMed-loaded hydrogels treated animals (p = 0.0139). Ejection fraction and cardiac work efficiency improved in the ASC/CMed-treated rats compared to saline treatment (p = 0.0151 and p = 0.0655, respectively). The intrapericardial injection of dECM hydrogels loaded with ASC and their secretome warrants a novel therapeutic modality to improve ventricular hemodynamics and reduce cardiac remodeling in DOX-IC. |
| format | Article |
| id | doaj-art-33676e1635944e10a80aa6e43de06e7f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-33676e1635944e10a80aa6e43de06e7f2025-02-02T12:24:44ZengNature PortfolioScientific Reports2045-23222025-01-0115111610.1038/s41598-025-87939-zIntrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathiesTácia Tavares Aquinas Liguori0Gabriel Romero Liguori1Viktor Sinkunas2Cristiano Jesus Correia3Raphael dos Santos Coutinho e Silva4Fernando Luiz Zanoni5Vera Demarchi Aiello6Martin Conrad Harmsen7Luiz Felipe Pinho Moreira8Instituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloInstituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloInstituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloInstituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloInstituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloInstituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloInstituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloDepartment of Pathology and Medical Biology, University of Groningen and University Medical Center GroningenInstituto do Coração (InCor), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São PauloAbstract Doxorubicin-induced cardiomyopathy (DOX-IC) is a significant and common complication in patients undergoing chemotherapy, leading to cardiac remodeling and reduced heart function. We hypothesized that the intrapericardial injection of hydrogels derived from the cardiac decellularized extracellular matrix (dECM) loaded with adipose tissue-derived stromal cells (ASC) and their secretome dampens or reverses the progression of DOX-IC. DOX-IC was induced in Wistar male rats through ten weekly intra-peritoneal injections of doxorubicin (cumulative dose: 18 mg/kg). We performed intrapericardial treatment in week five with dECM hydrogel loaded with ASC and their conditioned medium (CMed). The volume of intrapericardial injection was 2 ml/kg, the ASC density was 20 million/mL, while the hydrogel contained 100-fold concentrated CMed. Interstitial myocardial fibrosis was assessed by PicroSirius Red staining and hemodynamics parameters in pressure-volume loops. Compared to saline controls, interstitial myocardial fibrosis was reduced in ASC/CMed-loaded hydrogels treated animals (p = 0.0139). Ejection fraction and cardiac work efficiency improved in the ASC/CMed-treated rats compared to saline treatment (p = 0.0151 and p = 0.0655, respectively). The intrapericardial injection of dECM hydrogels loaded with ASC and their secretome warrants a novel therapeutic modality to improve ventricular hemodynamics and reduce cardiac remodeling in DOX-IC.https://doi.org/10.1038/s41598-025-87939-zDilated cardiomyopathy (DCM)DoxorubicinExtracellular matrixHydrogelsStem cellsCell therapy |
| spellingShingle | Tácia Tavares Aquinas Liguori Gabriel Romero Liguori Viktor Sinkunas Cristiano Jesus Correia Raphael dos Santos Coutinho e Silva Fernando Luiz Zanoni Vera Demarchi Aiello Martin Conrad Harmsen Luiz Felipe Pinho Moreira Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies Scientific Reports Dilated cardiomyopathy (DCM) Doxorubicin Extracellular matrix Hydrogels Stem cells Cell therapy |
| title | Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies |
| title_full | Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies |
| title_fullStr | Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies |
| title_full_unstemmed | Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies |
| title_short | Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies |
| title_sort | intrapericardial injection of hydrogels with asc and their secretome to treat dilated cardiomyopathies |
| topic | Dilated cardiomyopathy (DCM) Doxorubicin Extracellular matrix Hydrogels Stem cells Cell therapy |
| url | https://doi.org/10.1038/s41598-025-87939-z |
| work_keys_str_mv | AT taciatavaresaquinasliguori intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT gabrielromeroliguori intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT viktorsinkunas intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT cristianojesuscorreia intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT raphaeldossantoscoutinhoesilva intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT fernandoluizzanoni intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT verademarchiaiello intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT martinconradharmsen intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies AT luizfelipepinhomoreira intrapericardialinjectionofhydrogelswithascandtheirsecretometotreatdilatedcardiomyopathies |