Extracellular Vesicles in Cardiac Regeneration: Potential Applications for Tissues-on-a-Chip

Wagner, Karl T.; Nash, Trevor R.; Liu, Bohao; Vunjak‐Novakovic, Gordana; Radišić, Milica

doi:10.1016/j.tibtech.2020.08.005

Cited by 24 publications

(34 citation statements)

References 149 publications

(204 reference statements)

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“…VICs pretreated with male pre-TAVR serum showed reduced ability to deactivate when in male post-TAVR serum relative to VICs treated with female serum 156 . Therefore, growth factors, cytokines and exosomes in the cell environment should be included in sex-specific studies 157 . The source of sera is often not reported for cell culture experiments and, thus, chemically defined supplements should be used.…”

Section: Design Criteria For Sex-specific Modelsmentioning

confidence: 99%

A framework for developing sex-specific engineered heart models

et al. 2021

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The convergence of tissue engineering and patient-specific stem cell biology has enabled the engineering of in vitro tissue models that allow the study of patient-tailored treatment modalities. However, sex-related disparities in health and disease, from systemic hormonal influences to cellular-level differences, are often overlooked in stem cell biology, tissue engineering and preclinical screening. The cardiovascular system, in particular, shows considerable sex-related differences, which need to be considered in cardiac tissue engineering. In this Review, we analyse sex-related properties of the heart muscle in the context of health and disease, and discuss a framework for including sex-based differences in human cardiac tissue engineering. We highlight how sex-based features can be implemented at the cellular and tissue levels, and how sex-specific cardiac models could advance the study of cardiovascular diseases. Finally, we define design criteria for sex-specific cardiac tissue engineering and provide an outlook to future research possibilities beyond the cardiovascular system.

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Section: Design Criteria For Sex-specific Modelsmentioning

confidence: 99%

A framework for developing sex-specific engineered heart models

et al. 2021

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“…CM EVs have been found to act on endogenous CMs to reduce apoptosis, prevent hypertrophy, and reduce abnormalities in potassium channels through the action of biomolecular cargo such as HSP20, miR‐1, miR‐133a, and miR‐499. [ 12,49–55 ] They have also shown therapeutic efficacy in acting on cardiac fibroblasts (CFs) to reduce cardiac fibrosis via HSP20 and miR‐133a. [ 49,50,55 ] Acting on ECs in the heart, CM EVs may induce angiogenesis by promoting the proliferation and migration of EC into tubule formations via HSP20, miR‐143, and miR‐222.…”

Section: Evs In the Healthy And Diseased Heartmentioning

confidence: 99%

“…[ 12,49–55 ] They have also shown therapeutic efficacy in acting on cardiac fibroblasts (CFs) to reduce cardiac fibrosis via HSP20 and miR‐133a. [ 49,50,55 ] Acting on ECs in the heart, CM EVs may induce angiogenesis by promoting the proliferation and migration of EC into tubule formations via HSP20, miR‐143, and miR‐222. [ 49,56,57 ]…”

Section: Evs In the Healthy And Diseased Heartmentioning

confidence: 99%

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A New Role for Extracellular Vesicles in Cardiac Tissue Engineering and Regenerative Medicine

Wagner

Radišić

2021

Advanced NanoBiomed Research

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Cardiovascular diseases are the leading cause of death worldwide. Discovering new therapies to treat heart disease requires improved understanding of cardiac physiology at a cellular level. Extracellular vesicles (EVs) are plasma membrane‐bound nano‐ and microparticles secreted by cells and known to play key roles in intercellular communication, often through transfer of biomolecular cargo. Advances in EV research have established techniques for EV isolation from tissue culture media or biofluids, as well as standards for quantitation and biomolecular characterization. EVs released by cardiac cells are known to be involved in regulating cardiac physiology as well as in the progression of myocardial diseases. Due to difficulty accessing the heart in vivo, advanced in vitro cardiac “tissues‐on‐a‐chip” have become a recent focus for studying EVs in the heart. These physiologically relevant models are producing new insight into the role of EVs in cardiac physiology and disease while providing a useful platform for screening novel EV‐based therapeutics for cardiac tissue regeneration post‐injury. Numerous hurdles have stalled the clinical translation of EV therapeutics for heart patients, but tissue‐on‐a‐chip models are playing an important role in bridging the translational gap, improving mechanistic understanding of EV signaling in cardiac physiology, disease, and repair.

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“…To investigate the roles of EV-mediated signaling in cancer development, various approaches to track EVs in living animal subjects have been developed [ 36 , 37 ]. Even with advances in in vivo imaging that lower the cost and increase the throughput of animal studies [ 38 ], animal models are more costly and time-consuming than culture correlates and still have limited throughput; the traceability of EVs within a tumor-bearing animal over time still presents many challenges [ 39 , 40 ]. Xenograft models comprised of transplanted human cancer cells in immunodeficient rodents do not allow for proper tumor-stroma interactions or full vascularization and without an immune response are limited in translatability to human biology [ 41 , 42 , 43 ].…”

Section: Introduction: Evs In the Tmementioning

confidence: 99%

Visualizing Extracellular Vesicles and Their Function in 3D Tumor Microenvironment Models

Ural

Toomajian

Apu

et al. 2021

IJMS

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Extracellular vesicles (EVs) are cell-derived nanostructures that mediate intercellular communication by delivering complex signals in normal tissues and cancer. The cellular coordination required for tumor development and maintenance is mediated, in part, through EV transport of molecular cargo to resident and distant cells. Most studies on EV-mediated signaling have been performed in two-dimensional (2D) monolayer cell cultures, largely because of their simplicity and high-throughput screening capacity. Three-dimensional (3D) cell cultures can be used to study cell-to-cell and cell-to-matrix interactions, enabling the study of EV-mediated cellular communication. 3D cultures may best model the role of EVs in formation of the tumor microenvironment (TME) and cancer cell-stromal interactions that sustain tumor growth. In this review, we discuss EV biology in 3D culture correlates of the TME. This includes EV communication between cell types of the TME, differences in EV biogenesis and signaling associated with differing scaffold choices and in scaffold-free 3D cultures and cultivation of the premetastatic niche. An understanding of EV biogenesis and signaling within a 3D TME will improve culture correlates of oncogenesis, enable molecular control of the TME and aid development of drug delivery tools based on EV-mediated signaling.

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Extracellular Vesicles in Cardiac Regeneration: Potential Applications for Tissues-on-a-Chip

Cited by 24 publications

References 149 publications

A framework for developing sex-specific engineered heart models

A framework for developing sex-specific engineered heart models

A New Role for Extracellular Vesicles in Cardiac Tissue Engineering and Regenerative Medicine

Visualizing Extracellular Vesicles and Their Function in 3D Tumor Microenvironment Models

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