TY - JOUR
T1 - Intrapericardial injection of hydrogels with ASC and their secretome to treat dilated cardiomyopathies
AU - Liguori, Tácia Tavares Aquinas
AU - Liguori, Gabriel Romero
AU - Sinkunas, Viktor
AU - Correia, Cristiano Jesus
AU - Dos Santos Coutinho E Silva, Raphael
AU - Zanoni, Fernando Luiz
AU - Aiello, Vera Demarchi
AU - Harmsen, Martin Conrad
AU - Moreira, Luiz Felipe Pinho
N1 - © 2025. The Author(s).
PY - 2025/1/28
Y1 - 2025/1/28
N2 - 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.
AB - 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.
KW - Animals
KW - Hydrogels/chemistry
KW - Male
KW - Rats
KW - Doxorubicin/administration & dosage
KW - Rats, Wistar
KW - Cardiomyopathy, Dilated/drug therapy
KW - Secretome
KW - Adipose Tissue/metabolism
KW - Extracellular Matrix/metabolism
KW - Fibrosis
KW - Stromal Cells/metabolism
KW - Myocardium/metabolism
KW - Disease Models, Animal
KW - Pericardium/drug effects
U2 - 10.1038/s41598-025-87939-z
DO - 10.1038/s41598-025-87939-z
M3 - Article
C2 - 39875493
SN - 2045-2322
VL - 15
JO - Scientific Reports
JF - Scientific Reports
M1 - 3529
ER -