Human Cardiac Organoids for Disease Modeling

Nugraha, Bramasta; Buono, Michele Filippo; Boehmer, Lisa von; Hoerstrup, Simon P.; Emmert, Maximilian Y.

doi:10.1002/cpt.1286

Cited by 121 publications

(86 citation statements)

References 42 publications

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“…In Fig. 2 , we summarize the established organoids for human diseases in liver [ 21 , 40 - 44 ], lung [ 45 ], brain [ 24 , 27 , 28 , 46 - 49 ], lingual [ 30 ], colon [ 38 , 50 , 51 ], intestine [ 33 , 37 , 52 , 53 ], ovary [ 54 ], retina [ 55 ], kidney [ 56 , 57 ], esophagus [ 58 ], heart [ 59 ], breast [ 60 ], stomach [ 52 , 61 ], and pancreas [ 26 , 62 , 63 ].…”

Section: Development Of Non-clinical Testing Models Using Organoidsmentioning

confidence: 99%

Trends in the development of human stem cell-based non-animal drug testing models

Lee

2020

Korean J Physiol Pharmacol

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In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

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Section: Development Of Non-clinical Testing Models Using Organoidsmentioning

confidence: 99%

Trends in the development of human stem cell-based non-animal drug testing models

Lee

2020

Korean J Physiol Pharmacol

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“…Furthermore, since SARS-CoV-2 infections also cause dysfunction of disparate human organs including the lungs, heart, brain, kidney, intestine, etc., disease modeling by employing the human induced pluripotent stem cells (hiPSC) derived organoidmodel systems [30][31][32][33][34][35][36][37][38][39][40], lead the path towards the mechanisms underlying organ failures due to SARS-CoV-2 infections. Such experimental investigations using hiPSC derived organoid models could well generate molecular drug therapies to treat preemptive tissue damage by SARS-CoV-2 infections.…”

Section: Hypothesesmentioning

confidence: 99%

Potential combination endothelial progenitor cell and antiviral therapies for reversal of impaired angiogenesis induced by SARS-CoV-2 infection

Koka¹,

Ramdass²,

Reddy³

2020

Stem Cell Biol Res

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Late stage detection of COVID-19 disease pathogenesis induced by SARS-CoV-2 infection may prove to be fatal to the infected patients with the severity increasing, if inhibition of differentiation of hematopoietic endothelial progenitor cells, or their sustained deficiency, is not reversed. Antiviral drug treatments of such individuals need not necessarily resuscitate from a severe impairment of normal angiogenesis of the vascular endothelium. The virus targets the endothelial progenitor cells which co-express the hematopoietic stem cell marker CD34 and the angiotensin converting enzyme 2 (ACE2), latter being the host receptor for this pathogen. There is not an apparent segregation of CD34 and ACE2 antigens, strongly implicating inhibition of differentiation of virus infected progenitor cells. The embattled clinical condition of SARS-CoV-2 infected patients may well require a dual-mode endothelial progenitor cellular infusion and antiviral drug molecular therapies to stage a rapid clinical recovery. Umbilical cord blood derived CD34+ progenitor cells are the most optimal for rapid availability, harvesting and infusion into the severely ill infected patients, who are most likely to be non-responsive to solely antiviral drug treatments. This is about rapidly prepared allogeneic cell infusion therapy and not autologous cell transplantation which is impractical for these relatively acute and short-term conditions and treatments of SARS-CoV-2 infections. A combination progenitor cell and antiviral drug treatment is suggested for recovery and maintenance of normal angiogenesis of infected patients who may otherwise not survive. Hence the concept and its basis discussed needs to be urgently advanced to translation stage.

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“…To overcome these limitations and to enhance the understanding of biological mechanisms during the preclinical stage of the drug discovery process, a new concept based on culturing cells in three dimensions (3D) has been suggested [9]. It is believed that 3D human organoid models will eventually promote better understanding of human disease mechanisms, and help direct future treatments towards personalized medicine [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…The combination of these three cells types, therefore, may have the potential to significantly improve the cardiac research field through the development of human cardiac organoids. The latter can mimic various heart developmental stages, and can be used not only as a reliable platform for drug screening but also as a tool to imitate patient-specific cardiac conditions and assess the effectiveness of tailored personalized treatments [12].…”

Section: Introductionmentioning

confidence: 99%

Human Cardiac Organoids for Modeling Genetic Cardiomyopathy

Buono

Boehmer

Strang

et al. 2020

Cells

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Genetic cardiomyopathies are characterized by changes in the function and structure of the myocardium. The development of a novel in vitro model could help to better emulate healthy and diseased human heart conditions and may improve the understanding of disease mechanisms. In this study, for the first time, we demonstrated the generation of cardiac organoids using a triculture approach of human induced pluripotent stem-cell-derived cardiomyocytes (hiPS-CMs)—from healthy subjects and cardiomyopathy patients—human cardiac microvascular endothelial cells (HCMECs) and human cardiac fibroblasts (HCFs). We assessed the organoids’ suitability as a 3D cellular model for the representation of phenotypical features of healthy and cardiomyopathic hearts. We observed clear differences in structure and beating behavior between the organoid groups, depending on the type of hiPS-CMs (healthy versus cardiomyopathic) used. Organoids may thus prove a promising tool for the design and testing of patient-specific treatments as well as provide a platform for safer and more efficacious drug development.

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Human Cardiac Organoids for Disease Modeling

Cited by 121 publications

References 42 publications

Trends in the development of human stem cell-based non-animal drug testing models

Trends in the development of human stem cell-based non-animal drug testing models

Potential combination endothelial progenitor cell and antiviral therapies for reversal of impaired angiogenesis induced by SARS-CoV-2 infection

Human Cardiac Organoids for Modeling Genetic Cardiomyopathy

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