Cellular and Engineered Organoids for Cardiovascular Models

Thomas, Dilip; Choi, Suji; Alamana, Christina; Parker, Kevin Kit; Wu, Joseph C.

doi:10.1161/circresaha.122.320305

Cited by 44 publications

(71 citation statements)

References 218 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In summary, while we have achieved a number of advances with this platform, there is clearly room for further improvement as the entire field using hiPSC-CMs works towards fully recapitulating the physiology of adult myocardium 16 . Future work will focus on confirming the capabilities of this platform for in vitro toxicology and pharmacology, both to develop novel disease models for drug discovery 16,17 as well as to determine the potential to complement or supersede pre-clinical animal testing, when adequately validated. This includes working to improve upon multiple factors that can drive functional maturation, such as the implementation of a dynamic loading regime that can reproduce both preload and afterload.…”

Section: Discussionmentioning

confidence: 99%

FRESH™ 3D Bioprinted Cardiac Tissue, a Bioengineered Platform for in vitro Toxicology and Pharmacology

Finkel¹,

Sweet²,

Locke³

et al. 2023

Preprint

View full text Add to dashboard Cite

There is critical need for a predictive model of human cardiac physiology in the drug development process for assessment of compound toxicology and pharmacology. In vitro two-dimensional monolayer culture of cardiomyocytes provides biochemical and cellular readouts, and in vivo small and large animal models provide information on systemic cardiovascular response. However, there remains a significant gap in these models due to an incomplete recapitulation of adult human cardiovascular physiology, which results in more difficult safety interpretations. Recent efforts in developing in vitro models from engineered heart tissues have demonstrated potential for bridging this gap using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in a three-dimensional tissue structure. Here we advance this paradigm by implementing FRESH 3D bioprinting to build human cardiac tissues in a medium throughput, well-plate format with controlled tissue architecture, tailored cellular composition, and native-like physiological function, specifically in its adrenergic agonist drug response. To do this, we combined hiPSC-CMs, endothelial cells and fibroblasts in a cellular bioink and FRESH 3D bioprinted this mixture in the format of a thin tissue strip stabilized on a tissue fixture. Our results confirmed that FRESH 3D bioprinted cardiac tissues could be fabricated directly in a 24-well plate format, were composed of dense and highly aligned hiPSC-CMs at >600 million cells/mL, and within 14 days demonstrated reproducible calcium transients and fast conduction velocity of ~25 cm/s. Interrogation of these cardiac tissues with the β-adrenergic receptor agonist isoproterenol showed native-like positive chronotropic and inotropic responses, a combination of responses that is not typically observed in 2D monolayer models or standard 3D engineered heart tissue approaches. These results confirm that FRESH 3D bioprinted cardiac tissues represents a novel in vitro platform that enables early in vitro pharmacology and toxicology screening.

show abstract

Section: Discussionmentioning

confidence: 99%

FRESH™ 3D Bioprinted Cardiac Tissue, a Bioengineered Platform for in vitro Toxicology and Pharmacology

Finkel¹,

Sweet²,

Locke³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Cardiobundles were able to match contractile force, conduction velocity of action potentials, and cardiomyocyte size to mimic those of adult rat tissue [ 66 ]. These and related approaches to in vitro cardiac tissue engineering integrate biochemical, biophysical, and electromechanical stimuli to develop physiologically relevant systems for basic discovery and therapeutic benefit [ 67 – 69 ]. While cardiac MPSs confer the potential to study specific aspects of immune cell function in an appropriate dynamic environment, such as by incorporation of tissue resident MF, these applications have yet to be widely explored [ 70 ].…”

Section: Experimental Models and Assessment Of Inflammatory Pathophys...mentioning

confidence: 99%

Control of the post-infarct immune microenvironment through biotherapeutic and biomaterial-based approaches

Soni

D'Elia

Rodell

2023

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

Ischemic heart failure (IHF) is a leading cause of morbidity and mortality worldwide, for which heart transplantation remains the only definitive treatment. IHF manifests from myocardial infarction (MI) that initiates tissue remodeling processes, mediated by mechanical changes in the tissue (loss of contractility, softening of the myocardium) that are interdependent with cellular mechanisms (cardiomyocyte death, inflammatory response). The early remodeling phase is characterized by robust inflammation that is necessary for tissue debridement and the initiation of repair processes. While later transition toward an immunoregenerative function is desirable, functional reorientation from an inflammatory to reparatory environment is often lacking, trapping the heart in a chronically inflamed state that perpetuates cardiomyocyte death, ventricular dilatation, excess fibrosis, and progressive IHF. Therapies can redirect the immune microenvironment, including biotherapeutic and biomaterial-based approaches. In this review, we outline these existing approaches, with a particular focus on the immunomodulatory effects of therapeutics (small molecule drugs, biomolecules, and cell or cell-derived products). Cardioprotective strategies, often focusing on immunosuppression, have shown promise in pre-clinical and clinical trials. However, immunoregenerative therapies are emerging that often benefit from exacerbating early inflammation. Biomaterials can be used to enhance these therapies as a result of their intrinsic immunomodulatory properties, parallel mechanisms of action (e.g., mechanical restraint), or by enabling cell or tissue-targeted delivery. We further discuss translatability and the continued progress of technologies and procedures that contribute to the bench-to-bedside development of these critically needed treatments. Graphical Abstract

show abstract

“…Induced Pluripotent Stem Cells (iPSC) derived through reprogramming somatic cells with pluripotency factors (OCT3/4, SOX2, c-MYC, KLF4) can be differentiated to a specific cell line, including pericytes. 3D-culture systems of iPSC-derived cardiovascular cells have provided a novel in vitro model to study the interplay among different cell types and potentially develop new personalized treatments for congenital and acquired cardiac diseases (116,(143)(144)(145).…”

Section: Pericyte Generation From Ipscsmentioning

confidence: 99%

Approaches for the isolation and long-term expansion of pericytes from human and animal tissues

Alvino

Mohammed

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Pericytes surround capillaries in every organ of the human body. They are also present around the vasa vasorum, the small blood vessels that supply the walls of larger arteries and veins. The clinical interest in pericytes is rapidly growing, with the recognition of their crucial roles in controlling vascular function and possible therapeutic applications in regenerative medicine. Nonetheless, discrepancies in methods used to define, isolate, and expand pericytes are common and may affect reproducibility. Separating pure pericyte preparations from the continuum of perivascular mesenchymal cells is challenging. Moreover, variations in functional behavior and antigenic phenotype in response to environmental stimuli make it difficult to formulate an unequivocal definition of bona fide pericytes. Very few attempts were made to develop pericytes as a clinical-grade product. Therefore, this review is devoted to appraising current methodologies’ pros and cons and proposing standardization and harmonization improvements. We highlight the importance of developing upgraded protocols to create therapeutic pericyte products according to the regulatory guidelines for clinical manufacturing. Finally, we describe how integrating RNA-seq techniques with single-cell spatial analysis, and functional assays may help realize the full potential of pericytes in health, disease, and tissue repair.

show abstract

Cellular and Engineered Organoids for Cardiovascular Models

Cited by 44 publications

References 218 publications

FRESH™ 3D Bioprinted Cardiac Tissue, a Bioengineered Platform for in vitro Toxicology and Pharmacology

FRESH™ 3D Bioprinted Cardiac Tissue, a Bioengineered Platform for in vitro Toxicology and Pharmacology

Control of the post-infarct immune microenvironment through biotherapeutic and biomaterial-based approaches

Approaches for the isolation and long-term expansion of pericytes from human and animal tissues

Contact Info

Product

Resources

About