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Making progress towards 'heart in a dish' cardiac microtissue models

Frontiers in Cardiovascular Medicine cardiac microtissue models
Frontiers in Cardiovascular Medicine

Researchers Jasmeet S. Reyat, Abdullah O. Khan, et.al. recently published a new paper, 'Modelling the pathology and treatment of cardiac fibrosis in vascularised atrial and ventricular cardiac microtissues' in Frontiers in Cardiovascular Medicine. Their paper reports  an innovative method for creating cardiac microtissues. 

In this article, authors Jasmeet Reyat and Abdullah Khan discuss the potential of their research. 

What are cardiac microtissue models? 

A cardiac microtissue model is a tiny, three-dimensional structure created in the laboratory using human-induced pluripotent stem cells (hiPSCs). It closely mimics the cellular composition and function of specific parts of the human heart, such as the atria or ventricles. These microtissues are used to study heart diseases, test potential drug treatments, and investigate the effects of various conditions on the heart in a controlled and realistic environment. 

J.R. on Chamber-Specific Diseases 

J.R.: "Our model builds on a growing literature of cardiac microtissue models that have been published over the past couple of years. The development of an atrial cardiac microtissue adds novelty to explore chamber-specific diseases such as atrial fibrillation, the most common cardiac conduction disorder in the western world." 

A.K. on the 2-Step Approach 

A.K.: "One of the big challenges in the field of tissue engineering, or generating miniaturised models of key organs, is making a working blood vessel network. This is essential as large, complex 3D structures need a working vasculature to provide oxygen and other nutrients to keep all the cells alive and happy. 

Our approach is unique in that we have a 2-step process for making the microtissues. In our approach, we use a 3D scaffold called a hydrogel, which has been used in the past to make vessel networks, including in our previous work on replicating the bone marrow, to make a vascular structure. We then seed either atrial or ventricular cardiomyocytes, which have been separately differentiated in 2D using previously established protocols, onto that 3D structure. Over 10 days, they organise themselves into beating cultures. " 

Harnessing Reprogrammed Cells 

A.K.: "We derive all of these cells from reprogrammed adult cells which are called induced pluripotent stem cells (iPSCs). The benefit of this is you can use reprogrammed cells from patients in what are called ‘personalised’ medicine approaches. 

This type of approach is relatively inexpensive and easily scaled – we can produce hundreds of beating structures. Our hope is that this type of approach can be used to dissect disease effects in cells taken from, for example, patients with a high risk for cardiovascular disease (e.g. diabetes) and cardiomyopathies (genetic cardiovascular diseases)."

Challenges and Future Prospects 

A.K.: "We are still a long way from true, miniaturised models of the atria and ventricles. While we make nice vessel networks that support ventricular and atrial cardiomyocytes, actual heart tissue is extremely complex, with a multitude of different cell types. 

We are working towards this – and many of our contemporaries have made significant advances that we hope to incorporate into new technologies. It’s an exciting and fast-moving field where every step forward contributes to progress towards the ultimate goal of a ‘heart in a dish’." 

J.R.: " Combined with the fact that human pluripotent stem cells can be differentiated into multiple different cell types found in the heart, our future work will explore the cell-intrinsic cross-talk of multiple cell types within the microtissues and the development of further advanced microtissue models, e.g. containing immune cells." 

Final Thoughts 

Dr Jasmeet Reyat is a postdoctoral research scientist in IDRM's Simões Group. He co-authored this publication with Dr Abdullah Khan, a Sir Henry Wellcome Fellow at the MRC Weatherall Institute of Molecular Medicine. Both Drs Reyat and Khan have recently moved from the University of Birmingham, where the experimental portion of this work was conducted at the Institute of Cardiovascular Science.

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