RESUMEN
Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. ⢠Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. ⢠Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. ⢠Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.
Asunto(s)
Antineoplásicos , Enfermedades Cardiovasculares , Células Madre Pluripotentes Inducidas , Neoplasias , Humanos , Cardiotoxicidad/etiología , Miocitos Cardíacos , Evaluación Preclínica de Medicamentos , Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , OrganoidesRESUMEN
BACKGROUND: Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF. METHOD: In this study, we present a "system to system" (S2S) mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6) while maintaining its curative effect for MI. RESULTS: Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage. CONCLUSIONS: The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines.