Cardiovascular diseases (CVDs) are a series of diseases that often occur in the heart or blood vessels. In the past few decades, CVDs have become a major threat to human health and have become the leading cause of death all over the world. The symptoms for CVDs are different depending on the begin site, including but not limited to, heart failure, stroke, aortic aneurysms, chest pain, leg weakness, as well as venous thrombus. Meanwhile, a variety of risk factors, such as age, family history, genetic changes, tobacco use, and alcohol abuse, have been confirmed that are associated with CVD development. Previous studies have indicated that approximately 90% of CVD cases can be prevented if the establishment of good living habits to avoid these risk factors.
Currently, many kinds of methods for CVDs treating have been widely developed. Among them, surgery and medication are conventional strategies for alleviating the symptoms and reducing complications in patients with CVDs. However, existing treatments are not enough, and new therapies need to be further developed for CVD treatment safely and effectively.
Fig.1 Schematic overview of iPSC derivation from a patient or healthy subject reported so far in the literature. (Doss, 2019)
Induced pluripotent stem cells (iPSCs) can differentiate into different types of human cells, such as cardiac cells, liver cells, or neurons. Meanwhile, the rapid development of iPSC technology promotes the progression of an unlimited supply of pluripotent stem cells (PSCs) for tissue engineering, disease modeling, as well as drug screening.
Cardiovascular tissue engineering is essential to repairing blood vessels of CVDs. Moreover, a panel of advanced technologies, has been designed for facilitating the differentiation of iPSCs. For example, scaffolds, vascularization, in vitro microphysiological systems, and other external stimuli, are effective to promote differentiation.
Recently, iPSCs hold great promise for treating CVDs and developing new drugs or therapies in clinical applications. For instance, iPSCs have been broadly used for producing cardiomyocytes and establishing iPSC-based human models to reveal the mechanism of CVDs. A number of CVD-based models, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy, and Cardiac sodium channelopathies, have been established for analyzing the underlying pathogenesis of CVDs.
In addition, recent reports have demonstrated that microvesicles, especially for exosomes, derived from the iPSC-derived cardiomyocytes can regulate cellular function through the endogenous molecules, suggesting their therapeutic potential in the treatment of CVDs. Besides, numerous data have proved that iPSCs can bring a unique opportunity for CVD drug discovery and drug-induced cardiac toxicity assessment. Patients-derived iPSCs are more sensitive to the drug toxicity of in vitro culture system. Furthermore, the cardiotoxicity caused by drugs can be used to predict individual patients to novel drug candidates.
Fig.2 Differentiation steps from pluripotent stem cells to cardiomyocytes and their markers. (Themeli, 2013)
Given the global outbreak of CVDs and limited therapeutic options, novel iPSC-based therapies that improve the therapeutic effect of CVD are sorely required. The therapeutic use of iPSC has the potential to repair the damage and enhance the functions of the heart. In the past few years, up to 300 CVD trials have illustrated that most iPSC-derived differentiated cells are safe, but their efficacy still needs to be further evaluated in many large scales of clinical trials. Nowadays, a wide range of advanced cell isolation techniques, standard measurement techniques, as well as endpoint evaluation assays has been utilized in clinical trials. Moreover, many cell types, dosing, and delivery strategies have been generated for improving cell retention and survival rate in clinical application. Therefore, iPSC-based clinical studies are at a pivotal stage in the field in which small clinical trials must be assessed carefully to guide the larger efficacy trials and bring new iPSC-based CVD products to the market.
References
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