P407Vascularized heart tissue model for cardiac toxicity testing

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Abstract

Purpose

It is very challenging to study the effects of different drugs on cardiomyocytes. Neonatal rat cardiomyocytes (NRCs) are easy to obtain and they provide a practical source of cardiac cells to create a model to study the function of cardiac tissue in vitro. The aim of this study was to develop a vascularized heart tissue model.

Methods

In the heart tissue model two different supporting angiogenic structures were used. Structure 1 is a co-culture of fibroblasts and human umbilical vein endothelial cells (hUVECs) and structure 2 a co-culture of human adipose stem cells (hASCs) and hUVECs. NRCs were harvested from two to five-day-old rat hearts and plated on top of the angiogenic structures. The conditions for functional cardiomyocytes as well as for angiogenic tubule network formation were optimized. The cells were monitored repeatedly during the culture period. Also the functionality of the NRCs was studied with micro electrode array (MEA). Finally the cells were fixed and stained with anti-von Willebrand factor and anti-cardiac troponin T.

Results

Both angiogenic structures supported the viability and functionality of NRCs. In co-culture the contractile capacity of NRCs was maintained at least for 14 days whereas NRCs alone were contractile only for one week. For synchronously contracting areas fewer NRCs were needed in co-culture compared to NRCs alone. Angiogenic structure did not isolate the NRCs from the surface, but electrical activity could be obtained with MEA. Immunocytochemical experiments demonstrated anti-cardiac troponin T stained cardiac cells aligned nicely with angiogenic tubule network stained with anti-von Willebrand Factor.

Conclusions

Both angiogenic structures strongly supported the viability and functionality of NRCs. The developed vascularized heart tissue model could be used as a tool to study cardiac effects of different drugs and chemicals. The results of this study provide valuable data for the future studies aiming to accomplish completely human cell based cardiovascular model with cardiomyocytes differentiated from patient specific human induced pluripotent stem cells.

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