Cellular model systems to study cardiovascular injury from chemotherapy
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Cellular model systems to study cardiovascular injury from chemotherapy Hananeh Fonoudi1,2 · Paul W. Burridge1,2 Accepted: 26 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In spite of all the efforts for generating efficient pharmacological treatment options for cancer patients, the unwanted side effect of these substances on the cardiovascular system is becoming a major issue for cancer survivors. The fast pacing oncology field necessitate the quest for more accurate and reliable preclinical screenings. hiPSCs derived cardiomyocytes, endothelial and vascular smooth muscle cells provide unlimited source of physiologically relevant cells that could be used in the screening platforms. Cells derived from hiPSCs can measure drug induced alterations to different aspect of the heart including electrophysiology, contractility and structure. In this review, we will give an overview of the different in vivo and in vitro preclinical drug safety screenings. In following sections, we will focus on hiPSCs derived cardiomyocytes, endothelial and vascular smooth muscle cells and present the current knowledge of the application of these cells in unicellular cardiotoxicity assays. In the final part, we will focus on cardiac organoids as multi cell type platform and their role in cardiotoxicity screening of the chemotherapeutic drugs. Keywords Human induced pluripotent stem cells · Cardio-oncology · Precision medicine · Drug screening · Cardiotoxicity · Vascular toxicity
Highlights • Many chemotherapy agents show adverse side effect on
cardiovascular system; thus, it is crucial to develop more accurate systems for cardiotoxicity screenings. • Traditionally animal systems and non-cardiac human cell lines were used for preclinical testing; however, these systems cannot accurately recapitulate the human in vivo scenario due to lack of appropriate gene and protein expression and function. • Cardiovascular cells derived from human induced pluripotent stem cells could accurately predict the cardiac side effect of chemotherapeutic drugs.
* Paul W. Burridge [email protected] 1
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
2
• The application of multi cell type cardiac organoids in
the drug safety screening platforms could lead to development of safer treatment options for cancer patients.
Introduction Thanks to recent advances in oncology field new efficient drugs are being developed to save the lives of millions of people fighting with cancer all over the world. Unfortunately, many of these drugs cause adverse short-term or long-term effect on cardiovascular system such as heart failure, hypertension, arrhythmias, thrombogenesis and vasospasm [1]. This issue is becoming one of the major concerns of the physicians in the filed as the risk of mortality due to cardiovascular abnormalities is becoming higher than the r
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