Vascularized hiPSC-derived 3D cardiac microtissue on chip

Arslan, Ulgu; Brescia, Marcella; Meraviglia, Viviana; Nahon, Dennis M.; Helden, Ruben W.J. van; Stein, Jeroen M.; Hil, Francijna E. van den; Meer, Berend J. van; Cuenca, Marc Vila; Mummery, Christine L.; Orlova, Valeria V.

doi:10.1016/j.stemcr.2023.06.001

Cited by 19 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another very important organ to model in vitro is the heart and Christine Mummery (Leiden University Medical Centre, Netherlands) is a leading expert in this field ( Arslan et al, 2022 ). In the Mummery Group, cardiac micro-tissues are generated by either differentiating and mingling different heart-forming cell types or differentiating all the cell types of interest simultaneously with an appropriate 3D-culture protocol ( Arslan et al, 2023 ). The scientific progresses addressed by these four speakers are incredibly important to understand the physiology of the respective in vitro modelled organs, providing potent drug-screening platforms and in vitro -derived tissues for cell replacement therapies.…”

Section: Lecturesmentioning

confidence: 99%

Exploring stem cell frontiers: definitions, challenges, and perspectives for regenerative medicine

Dardano,

Lebek,

H. C. Tsang

2024

Biology Open

View full text Add to dashboard Cite

Each year, the European Summer School on Stem Cell Biology and Regenerative Medicine (SCSS) attracts early-career researchers and actively practicing clinicians who specialise in stem cell and regenerative biology. The 16th edition of this influential course took place from 12th to 19th September 2023 on the charming Greek island of Spetses. Focusing on important concepts and recent advances in stem cells, the distinguished faculty included experts spanning the spectrum from fundamental research to clinical trials to market-approved therapies. Alongside an academically intensive programme that bridges the various contexts of stem cell research, delegates were encouraged to critically address relevant questions in stem cell biology and medicine, including broader societal implications. Here, we present a comprehensive overview and key highlights from the SCSS 2023.

show abstract

Section: Lecturesmentioning

confidence: 99%

Exploring stem cell frontiers: definitions, challenges, and perspectives for regenerative medicine

Dardano,

Lebek,

H. C. Tsang

2024

Biology Open

View full text Add to dashboard Cite

show abstract

“…A recent model by Arslan et al involved pre-vascularized, tri-lineage cardiac microtissues (MT) cocultured with vascular cells within a fibrin hydrogel microfluidic and demonstrated perfusable vascular networks in and around the gel-laden cardiac MT. Further, perfusion of L-NAME or IL-1β induced functional changes in the vascularized cardiac MT, showing promising results as a model system of EC-CM paracrine signaling ( Arslan et al, 2023 ). Another similar non-organoid system was developed by King et al involving aggregation of hiPSC-CM, human cardiac microvascular EC (hCMVEC), and human left ventricular fibroblasts (hLVFB) in a three-dimensional fibrin matrix situated within a microfluidic device.…”

Section: Current Models Of Endothelial Dysfunction In Cardiac Develop...mentioning

confidence: 99%

Endothelial cell dysfunction in cardiac disease: driver or consequence?

Allbritton-King,

García-Cardeña

2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The vascular endothelium is a multifunctional cellular system which directly influences blood components and cells within the vessel wall in a given tissue. Importantly, this cellular interface undergoes critical phenotypic changes in response to various biochemical and hemodynamic stimuli, driving several developmental and pathophysiological processes. Multiple studies have indicated a central role of the endothelium in the initiation, progression, and clinical outcomes of cardiac disease. In this review we synthesize the current understanding of endothelial function and dysfunction as mediators of the cardiomyocyte phenotype in the setting of distinct cardiac pathologies; outline existing in vivo and in vitro models where key features of endothelial cell dysfunction can be recapitulated; and discuss future directions for development of endothelium-targeted therapeutics for cardiac diseases with limited existing treatment options.

show abstract

“…Unlike other tissues, the heart has limited capacity for regeneration, and endomyocardial biopsies are difficult to obtain [ 2 – 4 ]. Consequently, many researchers have endeavored to generate 3D cardiac models from induced pluripotent stem cells (iPSCs) to facilitate in vitro cardiac studies [ 2 , 5 ]. However, the most previously reported cardiac organoid (CO) models center on a 3D architecture constructed via the cardiac spheroid technique, which entails fusing iPSC-derived cardiomyocytes [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Song,

Choi,

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.

show abstract

Vascularized hiPSC-derived 3D cardiac microtissue on chip

Cited by 19 publications

References 24 publications

Exploring stem cell frontiers: definitions, challenges, and perspectives for regenerative medicine

Exploring stem cell frontiers: definitions, challenges, and perspectives for regenerative medicine

Endothelial cell dysfunction in cardiac disease: driver or consequence?

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Contact Info

Product

Resources

About