Human-induced pluripotent stem cells in cardiovascular research: current approaches in cardiac differentiation, maturation strategies, and scalable production

Abstract

Manifestations of cardiovascular diseases (CVDs) in a patient or a population differ based on inherent biological makeup, lifestyle, and exposure to environmental risk factors. These variables mean that therapeutic interventions may not provide the same benefit to every patient. In the context of CVDs, human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer an opportunity to model CVDs in a patient-specific manner. From a pharmacological perspective, iPSC-CM models can serve as go/no-go tests to evaluate drug safety. To develop personalized therapies for early diagnosis and treatment, human-relevant disease models are essential. Hence, to implement and leverage the utility of iPSC-CMs for large-scale treatment or drug discovery, it is critical to (i) carefully evaluate the relevant limitations of iPSC-CM differentiations, (ii) establish quality standards for defining the state of cell maturity, and (iii) employ techniques that allow scalability and throughput with minimal batch-to-batch variability. In this review, we briefly describe progress made with iPSC-CMs in disease modelling and pharmacological testing, as well as current iPSC-CM maturation techniques. Finally, we discuss current platforms for large-scale manufacturing of iPSC-CMs that will enable high-throughput drug screening applications.

Cellular and Engineered Organoids for Cardiovascular Models

“…Moreover, using iPSCderived cardiomyocytes (iPSC-CMs) and genome editing approaches, a wide number of monogenic and complex cardiac pathogenesis have been studied in vitro, providing newer insights into disease mechanisms. 6 Human iPSCs-CMs has also emerged as a cornerstone in drug Thomas et al Engineered Cardiovascular Models…”

Leveraging Spaceflight to Advance Cardiovascular Research on Earth

“…hiPSC-CMs have emerged as a robust model for studying the molecular and cellular mechanisms of cardiac pathophysiology. 108 In a proof-of-concept study, Wnorowski et al 57 demonstrated the feasibility of long-term cell culture of hiPSC-CMs on the ISS. Specifically, monolayers of beating hiPSC-CMs from 3 individuals were plated in BioCell, a fully contained cell culture vessel, and launched to the ISS on a SpaceX Dragon spacecraft.…”

The effects of xeno-free cryopreservation on the contractile properties of human iPSC derived cardiomyocytes

“…Therefore, it is essential to advance our models of cardiovascular diseases to develop better treatments for patients. Modeling cardiovascular diseases, screening for drug toxicities, and understanding heart developmental processes remain persistent challenges to the cardiovascular community due to their requirements of large quantities of well-characterized and highly uniform populations of human cardiomyocytes [42]. Although great strides have been made using animal models, there are key aspects of human cardiovascular physiology that these models fail to recapitulate.…”