The Stem Cell Niche for Cardiovascular Tissue Engineering

Background and Aim: To date, three-dimensional (3D) in vitro cell Conclusion: The results obtained in this study indicate that CSs can bettermimic the key characteristics of human heart morphology, biochemistryand pharmacology in vitro. As a result, we propose this CSs 3D model asa promising alternative to animal models and standard cell cultures withregard to mechanistic insights and prediction of toxic effects in humanheart tissue.systems have been considered as a promising alternative to the animalmodels to study cardiac biology and disease.Methods: In this present study, we have generated 3D in vitro cellcultures of the human heart, cardiac spheroids (CSs), by co-cultivationof the human primary or iPSC-derived cardiomyocytes, endothelial cellsand fibroblasts at the ratios approximating those present in vivo.Results: Our findings revealed that the microenvironment ( niche ) ofthese spheroids presented cellular organization, extracellular matrixand microcapillary network that better recapitulate the typical in thehuman heart compared to other existing in vitro models. These spheroidswere employed to study the dose-limiting cardiotoxicity of the commonanticancer drug doxorubicin (DOX). Viability/cytotoxicity assays indicatedose-dependent cytotoxic effects, which are inhibited by the nitric oxidesynthase (NOS) inhibitor L-NIO, and genetic inhibition of endothelialNOS, implicating peroxynitrous acid as a key damaging agent.

کلیدواژه ها:

Cardiac spheroids ، Niche ، iPSCs ، Cardiotoxicity ، Nitric oxide