Mesenchymal Stem Cell Derived Exosomes Ameliorates Doxorubicin-Induced Cardiotoxicity DOI Open Access

Sawdah Afiyah Ali,

Dinender K. Singla

Опубликована: Дек. 13, 2023

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there a need to discover innovative therapeutic approaches counteract DOX-induced (DIC). MSC-Exos have shown reduce apoptosis cardiac fibrosis promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of on ameliorating pyroptosis has not been investigated. In this current study H9c2 were first exposed DOX stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, further analysis performed through immunocytochemistry, western blotting, RT-PCR. Our data depicted post-treatment significantly (p<0.05) reduced HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, IL-18), executioner (GSDMD) DOX-treated cells. conclusion, our shows attenuates inflammation-induced vitro DIC model. findings indicate may serve promising intervention for mitigating DIC, they maintain capabilities MSCs while circumventing drawbacks associated traditional stem cell therapy.

Язык: Английский

MSC exosomes attenuate sterile inflammation and necroptosis associated with TAK1-pJNK-NFKB mediated cardiomyopathy in diabetic ApoE KO mice DOI Creative Commons

Abha Banerjee,

Dinender K. Singla

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 8, 2024

Introduction Diabetes is a debilitating disease that leads to complications like cardiac dysfunction and heart failure. In this study, we investigated the pathophysiology of diabetes-induced in mice with dyslipidemia. We hypothesize diabetes ApoE knockout (ApoE-/-) induces by increasing inflammation necroptosis. Methods ApoE-/- were divided into experimental groups: Control, Streptozotocin (STZ), STZ + MSC-Exo (mesenchymal stem cell-derived exosomes), STZ+MEF-Exo (Mouse embryonic fibroblast derived exosomes). At Day 42, assessed function, collected blood tissues. Heart tissue samples analyzed for inflammation, necroptosis, signaling mechanism, hypertrophy adverse structural remodeling using histology, immunohistochemistry, western blotting, RT-PCR, cytokine array TF array. Results Discussion treated developed diabetes, significantly (p<0.05) increased glucose body weight loss. These left ventricular internal diameter end diastole systole, decreased ejection fraction, fractional shortening. found significant expression inflammatory cytokines TNF- a, IL-6, IL-1a, IL-33 IL-10 expression. Diabetic also exhibited necroptosis marker infiltration monocytes macrophages. MSC-Exos showed recovery associated pathologies reduced glucose, recovered weight, secretion M2 polarized macrophages heart. TAK1-pJNK-NFKB improved function fibrosis compared diabetic mice. Treatment MEF-Exos did not play role attenuating cardiomyopathy as these treatment presented underlying observed Conclusion Thus, conclude develops mice, arising from remodeling, which ameliorated MSC-Exos, potential therapeutic cardiomyopathy.

Язык: Английский

Процитировано

3
Mesenchymal Stem Cell Derived Exosomes Ameliorates Doxorubicin-Induced Cardiotoxicity DOI Open Access

Sawdah Afiyah Ali,

Dinender K. Singla

Опубликована: Дек. 13, 2023

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there a need to discover innovative therapeutic approaches counteract DOX-induced (DIC). MSC-Exos have shown reduce apoptosis cardiac fibrosis promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of on ameliorating pyroptosis has not been investigated. In this current study H9c2 were first exposed DOX stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, further analysis performed through immunocytochemistry, western blotting, RT-PCR. Our data depicted post-treatment significantly (p<0.05) reduced HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, IL-18), executioner (GSDMD) DOX-treated cells. conclusion, our shows attenuates inflammation-induced vitro DIC model. findings indicate may serve promising intervention for mitigating DIC, they maintain capabilities MSCs while circumventing drawbacks associated traditional stem cell therapy.

Язык: Английский

Процитировано

2