Engineering Heart Morphogenesis

Mandrycky, Christian; Williams, Nisa P.; Batalov, Ivan; El‐Nachef, Danny; Bakker, Bernadette S. de; Davis, Jennifer; Kim, Deok Ho; DeForest, Cole A.; Zheng, Ying; Stevens, Kelly R.; Sniadecki, Nathan J.

doi:10.1016/j.tibtech.2020.01.006

Cited by 13 publications

(9 citation statements)

References 74 publications

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“…Heart embryonic development is one of the most complex physiological processes. It demands strict regulation of expression and activity of transcription factors, usually in time‐dependent manner in highly specified area of organ 180,181 . After birth, at cellular level, heart undergoes massive modifications, required for proper function in the adulthood.…”

Section: Discussion and Commentsmentioning

confidence: 99%

Adaptation of cardiomyogenesis to the generation and maturation of cardiomyocytes from human pluripotent stem cells

et al. 2022

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The advent of methods for efficient generation and cardiac differentiation of pluripotent stem cells opened new avenues for disease modelling, drug testing, and cell therapies of the heart. However, cardiomyocytes (CM) obtained from such cells demonstrate an immature, foetal‐like phenotype that involves spontaneous contractions, irregular morphology, expression of embryonic isoforms of sarcomere components, and low level of ion channels. These and other features may affect cellular response to putative therapeutic compounds and the efficient integration into the host myocardium after in vivo delivery. Therefore, novel strategies to increase the maturity of pluripotent stem cell‐derived CM are of utmost importance. Several approaches have already been developed relying on molecular changes that occur during foetal and postnatal maturation of the heart, its electromechanical activity, and the cellular composition. As a better understanding of these determinants may facilitate the generation of efficient protocols for in vitro acquisition of an adult‐like phenotype by immature CM, this review summarizes the most important molecular factors that govern CM during embryonic development, postnatal changes that trigger heart maturation, as well as protocols that are currently used to generate mature pluripotent stem cell‐derived cardiomyocytes.

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Section: Discussion and Commentsmentioning

confidence: 99%

Adaptation of cardiomyogenesis to the generation and maturation of cardiomyocytes from human pluripotent stem cells

et al. 2022

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“…Also, in vascular organoids, genetically modified stem cells could directly visualize in vivo the expression of tissue-specific cell markers, such as platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) or vascular endothelial growth factor (VEGF). The functionality of excitable and contractile tissues of organoids of the human brain and heart could be observed and visualized in real time using elegant and modern methods of optogenetics [46][47][48].…”

Section: Why Use Organoids In Space Research?mentioning

confidence: 99%

What can biofabrication do for space and what can space do for biofabrication?

Moroni

Tabury

Stenuit³

et al. 2022

Trends in Biotechnology

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Biofabrication in space is one of the novel promising and prospective research directions in the rapidly emerging field of space STEM. There are several advantages of biofabrication in space. Under microgravity, it is possible to engineer constructs using more fluidic channels and thus more biocompatible bioinks. Microgravity enables biofabrication of tissue and organ constructs of more complex geometries, thus facilitating novel scaffold-, label-, and nozzle-free technologies based on multi-levitation principles. However, when exposed to microgravity and cosmic radiation, biofabricated tissues could be used to study pathophysiological phenomena that will be useful on Earth and for deep space manned missions. Here, we provide leading concepts about the potential mutual benefits of the application of biofabrication technologies in space.Setting the stage: biofabrication, organoids, and space Biofabrication (see Glossary) technologies, and in particular bioprinting, hold the promise to create 3D in vitro models that exquisitely mimic the complexity of our tissues and organs [1]. These models can be used to study the physiology of tissues and organs exposed to a variety of environmental conditions, such as microgravity (μg) and radiation, as encountered in space. Knowledge acquired from these models is crucial to understand the biological effects of the space environment for long-term manned missions, such as outlined in the 'Moon village' and 'Mission to Mars' programs (

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“…There is increasing evidence that mechanical cues may govern several aspects of heart morphogenesis 11,12 . However, there are few models with which these findings can be substantiated in the context of human biology 13 . Tissue engineering strategies combined with human induced pluripotent stem cell (hiPSC) technology has enabled the development of diverse approaches for modeling structural and functional characteristics of cardiac tissue 14 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Perpendicular Shear Stresses Drive Transmural Helical Remodeling in Engineered Human Ventricular Models

Williams

Beussman

Foster

et al. 2022

Preprint

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Tissue engineering with human induced pluripotent stem cell-derived cardiomyocytes enables unique opportunities for creating physiological models of the heart in vitro. However, there are few approaches available that can recapitulate the complex structure-function relationships that govern cardiac function at the macroscopic organ level. Here, we report a down-scaled, conical human 3D ventricular model with controllable cellular organization using multilayered, patterned cardiac sheets. Tissue engineered ventricles whose cardiomyocytes were pre-aligned parallel or perpendicular to the long axis outperformed those whose cardiomyocytes were angled or randomly oriented. Notably, the inner layers of perpendicular cardiac sheets realigned over 4 days into a parallel orientation, creating a helical transmural architecture, whereas minimal remodeling occurred in the parallel or angled sheets. Finite element analysis of engineered ventricles demonstrated that circumferential alignment leads to maximal perpendicular shear stress at the inner layer, whereas longitudinal orientation leads to maximal parallel stress. We hypothesize that cellular remodeling occurs to reduce perpendicular shear stresses in myocardium. This advanced platform provides evidence that physical forces such as shear stress drive self-organization of cardiac architecture.

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Engineering Heart Morphogenesis

Cited by 13 publications

References 74 publications

Adaptation of cardiomyogenesis to the generation and maturation of cardiomyocytes from human pluripotent stem cells

Adaptation of cardiomyogenesis to the generation and maturation of cardiomyocytes from human pluripotent stem cells

What can biofabrication do for space and what can space do for biofabrication?

Perpendicular Shear Stresses Drive Transmural Helical Remodeling in Engineered Human Ventricular Models

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