Traditional drug screening models are often unable to faithfully recapitulate human physiology in health and disease. Linsitinib, a novel anti-cancer drug, showed promising results in pre-clinical models of Ewing Sarcoma...
Engineered cardiac tissues derived from human induced pluripotent stem cells (iPSCs) are increasingly used for drug discovery, pharmacology and in models of development and disease. While there are numerous platforms to engineer cardiac tissues, they often require expensive and nonconventional equipment and utilize complex video-processing algorithms. As a result, only specialized academic laboratories have been able to harness this technology. In addition, methodologies and tissue features have been challenging to reproduce between different groups and models. Here, we describe a facile technology (milliPillar) that covers the entire pipeline required for studies of engineered cardiac tissues. We include methodologies for (i) platform fabrication, (ii) cardiac tissue generation, (iii) electrical stimulation, (iv) automated real-time data acquisition, and (v) advanced video analyses. We validate these methodologies and demonstrate the versatility of the platform by showcasing the fabrication of tissues in different hydrogel materials and using cardiomyocytes derived from different iPSC lines in combination with different types of stromal cells. We also validate the long-term culture of tissues within the platform and provide protocols for automated analysis of force generation and calcium flux using both brightfield and fluorescence imaging. Lastly, we demonstrate the compatibility of the milliPillar platform with electromechanical stimulation to enhance cardiac tissue function. We expect that this resource will provide a valuable and userfriendly tool for the generation and real-time assessment of engineered human cardiac tissues for basic and translational studies.
The convergence of tissue engineering and patient-specific stem cell biology has enabled the engineering of in vitro tissue models that allow the study of patient-tailored treatment modalities. However, sex-related disparities in health and disease, from systemic hormonal influences to cellular-level differences, are often overlooked in stem cell biology, tissue engineering and preclinical screening. The cardiovascular system, in particular, shows considerable sex-related differences, which need to be considered in cardiac tissue engineering. In this Review, we analyse sex-related properties of the heart muscle in the context of health and disease, and discuss a framework for including sex-based differences in human cardiac tissue engineering. We highlight how sex-based features can be implemented at the cellular and tissue levels, and how sex-specific cardiac models could advance the study of cardiovascular diseases. Finally, we define design criteria for sex-specific cardiac tissue engineering and provide an outlook to future research possibilities beyond the cardiovascular system.
Current interventions fail to recover injured myocardium after infarction and prompt the need for development of cardioprotective strategies. Of increasing interest is the therapeutic use of microRNAs to control gene expression through specific targeting of mRNAs. In this Review, we discuss current microRNA-based therapeutic strategies, describing the outcomes and limitations of key microRNAs with a focus on target cell types and molecular pathways. Last, we offer a perspective on the outlook of microRNA therapies for myocardial infarction, highlighting the outstanding challenges and emerging strategies.
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