Building Multi-Dimensional Induced Pluripotent Stem Cells-Based Model Platforms to Assess Cardiotoxicity in Cancer Therapies

Frontiers in Pharmacology

Nazish Sayed¹  Dilip Thomas²  Sushma Shenoy³ 

[1] Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States;Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, United States;Stanford Cardiovascular Institute, Stanford, CA, United States;

关键词: induced pluripotent stem cells;    cardiomyocytes;    cancer drugs;    multicellular crosstalk;    3D platforms;    cardio-oncology;   

DOI  :  10.3389/fphar.2021.607364

来源: DOAJ

【 摘 要 】

Cardiovascular disease (CVD) complications have contributed significantly toward poor survival of cancer patients worldwide. These complications that result in myocardial and vascular damage lead to long-term multisystemic disorders. In some patient cohorts, the progression from acute to symptomatic CVD state may be accelerated due to exacerbation of underlying comorbidities such as obesity, diabetes and hypertension. In such situations, cardio-oncologists are often left with a clinical predicament in finding the optimal therapeutic balance to minimize cardiovascular risks and maximize the benefits in treating cancer. Hence, prognostically there is an urgent need for cost-effective, rapid, sensitive and patient-specific screening platform to allow risk-adapted decision making to prevent cancer therapy related cardiotoxicity. In recent years, momentous progress has been made toward the successful derivation of human cardiovascular cells from induced pluripotent stem cells (iPSCs). This technology has not only provided deeper mechanistic insights into basic cardiovascular biology but has also seamlessly integrated within the drug screening and discovery programs for early efficacy and safety evaluation. In this review, we discuss how iPSC-derived cardiovascular cells have been utilized for testing oncotherapeutics to pre-determine patient predisposition to cardiovascular toxicity. Lastly, we highlight the convergence of tissue engineering technologies and precision medicine that can enable patient-specific cardiotoxicity prognosis and treatment on a multi-organ level.

【 授权许可】

Unknown