Dissecting coronary angiogenesis: 3D co-culture of cardiomyocytes with endothelial or mesenchymal cells

Garzoni, Luciana Ribeiro; Rossi, Maria Isabel D.; Barros, A.; Guarani, Virgínia; Kéramidas, Michelle; Balottin, Luciene B.L.; Adesse, Daniel; Takiya, Christina Maeda; Manso, Pedro Paulo de Abreu; Otazú, Ivone B.; Meirelles, Maria de Nazareth Leal de; Borojević, Radovan

doi:10.1016/j.yexcr.2009.09.016

Cited by 57 publications

(38 citation statements)

References 25 publications

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“…This has been supported further by several hiPSC-CM-based studies showing that supporting cell types provide extracellular matrix microenvironment, incorporate angiogenic signaling, enhance microtissue assembly, and improve maturation of cardiac microtissues (25–31). Furthermore, the addition of vascular cell types to cardiac microtissues can model aspects of coronary angiogenesis and provide a functional benefit in heart repair by connecting to the host vasculature after transplantation (19, 23, 31, 32). By targeting specific hiPSC-CM functions/properties, tissue-engineered cardiac systems have been advantageous for the development of more sensitive drug testing models and improved cell delivery strategies.…”

Section: Introductionmentioning

confidence: 99%

Inspiration from heart development: Biomimetic development of functional human cardiac organoids

et al. 2017

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Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair.

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Section: Introductionmentioning

confidence: 99%

Inspiration from heart development: Biomimetic development of functional human cardiac organoids

et al. 2017

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“…More recently, “microtissues” and “macrotissues” have been formed in vitro from the re-assembly of cells dissociated from tissues, from cell lines and from stem cells (Garzoni et al 2009; Kelm et al 2010; Kelm et al 2006; Langenbach et al 2010). Such scaffold-free, 3D cell culture systems are thought to more closely resemble the physiological tissue environment by enabling greater cell–cell and cell–matrix interactions than conventional monolayer culture techniques and provide a platform for the study of cell behaviors such as proliferation, differentiation, apoptosis and extracellular matrix (ECM) and biomolecule production in the absence of exogenous, artificial matrices that may impede intrinsic cell behaviors.…”

Section: Introductionmentioning

confidence: 99%

Scaffold-free culture of mesenchymal stem cell spheroids in suspension preserves multilineage potential

2011

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While traditional cell culture methods have relied on growing cells as monolayers, three-dimensional (3D) culture systems can provide a convenient in vitro model for the study of complex cell–cell and cell–matrix interactions in the absence of exogenous substrates and may benefit the development of regenerative medicine strategies. In this study, mesenchymal stem cell (MSC) spheroids, or “mesenspheres”, of different sizes, were formed using a forced aggregation technique and maintained in suspension culture for extended periods of time thereafter. Cell proliferation and differentiation potential within mesenspheres and dissociated cells retrieved from spheroids were compared to conventional adherent monolayer cultures. Mesenspheres maintained in growth medium exhibited no evidence of cell necrosis or differentiation, while mesenspheres in differentiation media exhibited differentiation similar to conventional 2D culture methods based on histological markers of osteogenic and adipogenic commitment. Furthermore, when plated onto tissue culture plates, cells that had been cultured within mesenspheres in growth medium recovered morphology typical of cells cultured continuously in adherent monolayers and retained their capacity for multilineage differentiation potential. In fact, more robust matrix mineralization and lipid vacuole content were evident in recovered MSCs when compared to monolayers, suggesting enhanced differentiation by cells cultured as 3D spheroids. Thus, this study demonstrates the development of a 3D culture system for mesenchymal stem cells that may circumvent limitations associated with conventional monolayer cultures and enhance the differentiation potential of multipotent cells.

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“…Freshly isolated cardiomyocytes have a tendency to form spheroid aggregates in suspension. When MSCs are added to such a mixture, they appear to co-localize with regions rich in fibronectin, a pro-angiogenic ECM component, and express CD31, followed by vWF [78]. Similar studies examining MSC and cardiomyocyte interactions have demonstrated cardiomyocyte differentiation of MSCs when co-cultured with cardiomyocytes [79].…”

Section: Msc: Most Social Cell?mentioning

confidence: 80%

Mesenchymal Stem Cells for Cardiovascular Regeneration

Kuraitis

Ruel

Suuronen

2011

Cardiovasc Drugs Ther

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Despite recent studies suggesting that the heart has instrinsic mechanisms of self-regeneration following myocardial infarction, it cannot regenerate itself to an optimal level. Mesenchymal stem cells (MSCs) are currently being investigated for regeneration of mesenchyme-derived tissues, such as bone, cartilage and tendon. In vitro evidence suggests that MSCs can also differentiate into cardiomyogenic and vasculogenic lineages, offering another cell source for cardiovascular regeneration. In vivo, MSCs may contribute to the re-growth and protection of vasculature and cardiomyocytes, mediated by paracrine actions, and/or persist within the myocardium in a differentiated state; although proof of cardiomyocytic phenotype and functional integration remains elusive. Herein, we review the evidence of MSCs as a cell source for cardiovascular regeneration, as well as their limitations that may prevent them from being effectively used in the clinic.

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Dissecting coronary angiogenesis: 3D co-culture of cardiomyocytes with endothelial or mesenchymal cells

Cited by 57 publications

References 25 publications

Inspiration from heart development: Biomimetic development of functional human cardiac organoids

Inspiration from heart development: Biomimetic development of functional human cardiac organoids

Scaffold-free culture of mesenchymal stem cell spheroids in suspension preserves multilineage potential

Mesenchymal Stem Cells for Cardiovascular Regeneration

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