Journal of Cardiovascular Development and Disease

Research

15 pages, 2620 KiB

Open AccessArticle

Designing a 3D Printing Based Auxetic Cardiac Patch with hiPSC-CMs for Heart Repair

by Olga Brazhkina, Jeong Hun Park, Hyun-Ji Park, Sruti Bheri, Joshua T. Maxwell, Scott J. Hollister and Michael E. Davis

J. Cardiovasc. Dev. Dis. 2021, 8(12), 172; https://doi.org/10.3390/jcdd8120172 - 03 Dec 2021

Cited by 4 | Viewed by 4094

Abstract

Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. [...] Read more.

Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. These patches can be enhanced with the application of an auxetic design, which has a negative Poisson’s ratio and can be modified to suit the mechanics of the infarct and surrounding cardiac tissue. Here, we examined multiple auxetic models (orthogonal missing rib and re-entrant honeycomb in two orientations) with tunable mechanical properties as a cardiac patch substrate. Further, we demonstrated that 3D printing based auxetic cardiac patches of varying thicknesses (0.2, 0.4, and 0.6 mm) composed of polycaprolactone and gelatin methacrylate can support induced pluripotent stem cell-derived cardiomyocyte function for 14-day culture. Taken together, this work shows the potential of cellularized auxetic cardiac patches as a suitable tissue engineering approach to treating cardiovascular disease. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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12 pages, 2324 KiB

Open AccessArticle

Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading

by Sruti Bheri, Brandon P. Kassouf, Hyun-Ji Park, Jessica R. Hoffman and Michael E. Davis

J. Cardiovasc. Dev. Dis. 2021, 8(11), 135; https://doi.org/10.3390/jcdd8110135 - 22 Oct 2021

Cited by 6 | Viewed by 2266

Abstract

Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carry cardioprotective cargo, including microRNA (miRNA), within [...] Read more.

Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carry cardioprotective cargo, including microRNA (miRNA), within a complex membrane and improve cardiac outcomes similar to that of their parent cells. However, miRNA loading efficiency is low, and sEV yield and cargo composition vary with parent cell conditions, minimizing sEV potency. Synthetic mimics allow for cargo-loading control but consist of much simpler membranes, often suffering from high immunogenicity and poor stability. Here, we aim to combine the benefits of sEVs and synthetic mimics to develop sEV-like vesicles (ELVs) with customized cargo loading. We developed a modified thin-film hydration (TFH) mechanism to engineer ELVs from CPC-derived sEVs with pro-angiogenic miR-126 encapsulated. Characterization shows miR-126+ ELVs are similar in size and structure to sEVs. Upon administration to cardiac endothelial cells (CECs), ELV uptake is similar to sEVs too. Further, when functionally validated with a CEC tube formation assay, ELVs significantly improve tube formation parameters compared to sEVs. This study shows TFH-ELVs synthesized from sEVs allow for select miRNA loading and can improve in vitro cardiac outcomes. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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Review

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11 pages, 1538 KiB

Open AccessReview

Cardiac Organoids and Gastruloids to Study Physio-Pathological Heart Development

by Marisa E. Jaconi and Michel Puceat

J. Cardiovasc. Dev. Dis. 2021, 8(12), 178; https://doi.org/10.3390/jcdd8120178 - 10 Dec 2021

Cited by 1 | Viewed by 3609

Abstract

Ethical issues restrict research on human embryos, therefore calling for in vitro models to study human embryonic development including the formation of the first functional organ, the heart. For the last five years, two major models have been under development, namely the human [...] Read more.

Ethical issues restrict research on human embryos, therefore calling for in vitro models to study human embryonic development including the formation of the first functional organ, the heart. For the last five years, two major models have been under development, namely the human gastruloids and the cardiac organoids. While the first one mainly recapitulates the gastrulation and is still limited to investigate cardiac development, the second one is becoming more and more helpful to mimic a functional beating heart. The review reports and discusses seminal works in the fields of human gastruloids and cardiac organoids. It further describes technologies which improve the formation of cardiac organoids. Finally, we propose some lines of research towards the building of beating mini-hearts in vitro for more relevant functional studies. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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14 pages, 316 KiB

Open AccessEditor’s ChoiceReview

Cardiac Tissue Engineering for the Treatment of Myocardial Infarction

by Dongmin Yu, Xiaowei Wang and Lei Ye

J. Cardiovasc. Dev. Dis. 2021, 8(11), 153; https://doi.org/10.3390/jcdd8110153 - 08 Nov 2021

Cited by 6 | Viewed by 2645

Abstract

Poor cell engraftment rate is one of the primary factors limiting the effectiveness of cell transfer therapy for cardiac repair. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic [...] Read more.

Poor cell engraftment rate is one of the primary factors limiting the effectiveness of cell transfer therapy for cardiac repair. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic effects of the treatment for myocardial infarction. This mini-review summarizes the recent progress in cardiac tissue engineering of cardiovascular cells from differentiated human pluripotent stem cells (PSCs), highlights their therapeutic applications for the treatment of myocardial infarction, and discusses the present challenges of cardiac tissue engineering and possible future directions from a clinical perspective. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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32 pages, 1693 KiB

Open AccessReview

Human Induced Pluripotent Stem Cell-Derived Vascular Cells: Recent Progress and Future Directions

by Jee Eun Oh, Cholomi Jung and Young-sup Yoon

J. Cardiovasc. Dev. Dis. 2021, 8(11), 148; https://doi.org/10.3390/jcdd8110148 - 04 Nov 2021

Cited by 9 | Viewed by 3814

Abstract

Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). [...] Read more.

Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). In particular, hiPSC-derived ECs have shown robust potential for promoting neovascularization in animal models of cardiovascular diseases, potentially achieving significant and sustained therapeutic benefits. However, the use of hiPSC-derived SMCs that possess high therapeutic relevance is a relatively new area of investigation, still in the earlier investigational stages. In this review, we first discuss different methodologies to derive vascular cells from hiPSCs with a particular emphasis on the role of key developmental signals. Furthermore, we propose a standardized framework for assessing and defining the EC and SMC identity that might be suitable for inducing tissue repair and regeneration. We then highlight the regenerative effects of hiPSC-derived vascular cells on animal models of myocardial infarction and hindlimb ischemia. Finally, we address several obstacles that need to be overcome to fully implement the use of hiPSC-derived vascular cells for clinical application. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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25 pages, 2280 KiB

Open AccessEditor’s ChoiceReview

Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering

by Astha Khanna, Maedeh Zamani and Ngan F. Huang

J. Cardiovasc. Dev. Dis. 2021, 8(11), 137; https://doi.org/10.3390/jcdd8110137 - 22 Oct 2021

Cited by 28 | Viewed by 7532

Abstract

Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic [...] Read more.

Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic scaffolding structure characterized by tissue-specific biochemical, biophysical, and mechanical properties that modulates cellular behavior and activates highly regulated signaling pathways. In light of technological advancements, biomaterial-based scaffolds have been developed that better mimic physiological ECM properties, provide signaling cues that modulate cellular behavior, and form functional tissues and organs. In this review, we summarize the in vitro, pre-clinical, and clinical research models that have been employed in the design of ECM-based biomaterials for cardiovascular regenerative medicine. We highlight the research advancements in the incorporation of ECM components into biomaterial-based scaffolds, the engineering of increasingly complex structures using biofabrication and spatial patterning techniques, the regulation of ECMs on vascular differentiation and function, and the translation of ECM-based scaffolds for vascular graft applications. Finally, we discuss the challenges, future perspectives, and directions in the design of next-generation ECM-based biomaterials for cardiovascular tissue engineering and clinical translation. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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16 pages, 25841 KiB

Open AccessEditor’s ChoiceReview

Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration

by Angello Huerta Gomez, Sanika Joshi, Yong Yang, Johnathan D. Tune, Ming-Tao Zhao and Huaxiao Yang

J. Cardiovasc. Dev. Dis. 2021, 8(10), 125; https://doi.org/10.3390/jcdd8100125 - 30 Sep 2021

Cited by 5 | Viewed by 3077

Abstract

The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling [...] Read more.

The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling rely on animal models and a few clinical studies, which significantly bottleneck the understanding of Notch signaling-associated human cardiovascular development and disease. Recent advances in the bioengineering systems and human pluripotent stem cell-derived cardiovascular cells pave the way to decipher the role of Notch signaling in cardiovascular-related cells (endothelial cells, cardiomyocytes, smooth muscle cells, fibroblasts, and immune cells), and intercellular crosstalk in the physiological, pathological, and regenerative context of the complex human cardiovascular system. In this review, we first summarize the significant roles of Notch signaling in individual cardiac cell types. We then cover the bioengineering systems of microfluidics, hydrogel, spheroid, and 3D bioprinting, which are currently being used for modeling and studying Notch signaling in the cardiovascular system. At last, we provide insights into ancillary supports of bioengineering systems, varied types of cardiovascular cells, and advanced characterization approaches in further refining Notch signaling in cardiovascular development, disease, and regeneration. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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Other

Jump to: Research, Review

13 pages, 5984 KiB

Open AccessBrief Report

Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes

by Qianliang Yuan, Renee G. C. Maas, Ellen C. J. Brouwer, Jiayi Pei, Christian Snijders Blok, Marko A. Popovic, Nanne J. Paauw, Niels Bovenschen, Jesper Hjortnaes, Magdalena Harakalova, Pieter A. Doevendans, Joost P. G. Sluijter, Jolanda van der Velden and Jan W. Buikema

J. Cardiovasc. Dev. Dis. 2022, 9(2), 43; https://doi.org/10.3390/jcdd9020043 - 27 Jan 2022

Cited by 3 | Viewed by 4149

Abstract

Contractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during [...] Read more.

Contractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during mitosis resulting in cellular or nuclear division in a source of proliferating human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed that both mono- and binuclear hiPSC-CMs give rise to mononuclear daughter cells or binuclear progeny. Within this source of highly proliferative hiPSC-CMs, treated with the CHIR99021 small molecule, we found that Wnt and Hippo signaling was more present when compared to metabolic matured non-proliferative hiPSC-CMs and adult human heart tissue. Furthermore, we found that CHIR99021 increased the efficiency of non-viral vector incorporation in high-proliferative hiPSC-CMs, in which fluorescent transgene expression became present after the chromosomal segregation (M phase). This study provides a tool for gene manipulation studies in hiPSC-CMs and engineered cardiac tissue. Moreover, our data illustrate that there is a complex biology behind the cellular and nuclear division of mono- and binuclear CMs, with a shared-phenomenon of sarcomere disassembly during mitosis. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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