ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure

Madonna, Rosalinda; Laake, Linda W. van; Bøtker, Hans Erik; Davidson, Sean M.; Caterina, Raffaele De; Engel, Felix B.; Eschenhagen, Thomas; Fernández-Avilés, F; Hausenloy, Derek J.; Hulot, Jean‐Sébastien; Lecour, Sandrine; Leor, Jonathan; Menasché, Philippe; Pesce, Maurizio; Perrino, Cinzia; Prunier, Fabrice; Linthout, Sophie Van; Ytrehus, Kirsti; Zimmermann, Wolfram H.; Ferdinándy, Péter; Sluijter, Joost P.G.

doi:10.1093/cvr/cvz010

Cited by 103 publications

(108 citation statements)

References 151 publications

(178 reference statements)

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“…However, due to organ donor shortage and to the high incidence of IHD, alternative strategies are urgently needed. Cardiac tissue engineering (CTE) aiming at developing three-dimensional myocardium-like scaffolds for therapeutic use by combining cells, synthetic or natural biomaterials, and biomimetic signals is rapidly emerging as the most promising alternative to heart transplant (Vunjak-Novakovic et al, 2010;Massai et al, 2013;Feric and Radisic, 2016;Stoppel et al, 2016;Fujita and Zimmermann, 2017;Weinberger et al, 2017;Madonna et al, 2019). Among biomaterials, decellularized tissues are emerging as the most promising scaffolds for regenerative medicine, due to their potential to provide natural biological cues (Yaling et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration

Belviso

Romano

Sacco

et al. 2020

Front. Bioeng. Biotechnol.

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The complex and highly organized environment in which cells reside consists primarily of the extracellular matrix (ECM) that delivers biological signals and physical stimuli to resident cells. In the native myocardium, the ECM contributes to both heart compliance and cardiomyocyte maturation and function. Thus, myocardium regeneration cannot be accomplished if cardiac ECM is not restored. We hypothesize that decellularized human skin might make an easily accessible and viable alternate biological scaffold for cardiac tissue engineering (CTE). To test our hypothesis, we decellularized specimens of both human skin and human myocardium and analyzed and compared their composition by histological methods and quantitative assays. Decellularized dermal matrix was then cut into 600-µm-thick sections and either tested by uniaxial tensile stretching to characterize its mechanical behavior or used as three-dimensional scaffold to assess its capability to support regeneration by resident cardiac progenitor cells (hCPCs) in vitro. Histological and quantitative analyses of the dermal matrix provided evidence of both effective decellularization with preserved tissue architecture and retention of ECM proteins and growth factors typical of cardiac matrix. Further, the elastic modulus of the dermal matrix resulted comparable with that reported in literature for the human myocardium and, when tested in vitro, dermal matrix resulted a comfortable and protective substrate promoting and supporting hCPC engraftment, survival and cardiomyogenic potential. Our study provides compelling evidence that dermal matrix holds promise as a fully autologous and cost-effective biological scaffold for CTE.

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Section: Introductionmentioning

confidence: 99%

Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration

Belviso

Romano

Sacco

et al. 2020

Front. Bioeng. Biotechnol.

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“…Cardiovascular diseases (CVD) are the leading cause of death worldwide [1] and deteriorate considerably the quality of many patient's life. To enhance prognosis and wellbeing of patients, a variety of cells were evaluated for their therapeutic potential in experimental and clinical studies, like cardiosphere-derived cells, cardiac progenitor cells, and mesenchymal stromal (MSC) cells from bone marrow, adipose tissue and other sources [2][3][4][5][6][7][8]. Another unique cardiac cell type are the human cardiacderived adherent proliferating (CardAP) cells, which are generated by outgrowth cultures of endomyocardial biopsies [9].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes

et al. 2019

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Background: Nano-sized vesicles, so called extracellular vesicles (EVs), from regenerative cardiac cells represent a promising new therapeutic approach to treat cardiovascular diseases. However, it is not yet sufficiently understood how cardiac-derived EVs facilitate their protective effects. Therefore, we investigated the immune modulating capabilities of EVs from human cardiac-derived adherent proliferating (CardAP) cells, which are a unique cell type with proven cardioprotective features. Results: Differential centrifugation was used to isolate EVs from conditioned medium of unstimulated or cytokinestimulated (IFNγ, TNFα, IL-1β) CardAP cells. The derived EVs exhibited typical EV-enriched proteins, such as tetraspanins, and diameters mostly of exosomes (< 100 nm). The cytokine stimulation caused CardAP cells to release smaller EVs with a lower integrin ß1 surface expression, while the concentration between both CardAP-EV variants was unaffected. An exposure of either CardAP-EV variant to unstimulated human peripheral blood mononuclear cells (PBMCs) did not induce any T cell proliferation, which indicates a general low immunogenicity. In order to evaluate immune modulating properties, PBMC cultures were stimulated with either Phytohemagglutin or anti-CD3. The treatment of those PBMC cultures with either CardAP-EV variant led to a significant reduction of T cell proliferation, pro-inflammatory cytokine release (IFNγ, TNFα) and increased levels of active TGFβ. Further investigations identified CD14 + cells as major recipient cell subset of CardAP-EVs. This interaction caused a significant lower surface expression of HLA-DR, CD86, and increased expression levels of CD206 and PD-L1. Additionally, EV-primed CD14 + cells released significantly more IL-1RA. Notably, CardAP-EVs failed to modulate anti-CD3 triggered T cell proliferation and pro-inflammatory cytokine release in monocultures of purified CD3 + T cells. Subsequently, the immunosuppressive feature of CardAP-EVs was restored when anti-CD3 stimulated purified CD3 + T cells were co-cultured with EV-primed CD14 + cells. Beside attenuated T cell proliferation, those cultures also exhibited a significant increased proportion of regulatory T cells. Conclusions: CardAP-EVs have useful characteristics that could contribute to enhanced regeneration in damaged cardiac tissue by limiting unwanted inflammatory processes. It was shown that the priming of CD14 + immune cells by CardAP-EVs towards a regulatory type is an essential step to attenuate significantly T cell proliferation and proinflammatory cytokine release in vitro.

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“…In addition, the cell-seeded collagen matrix allowed to normalize cardiac wall stress in injured regions, thus limiting ventricular remodeling and improving diastolic function. Subsequent studies combined the use of biodegradable cell-seeded hybrid scaffolds with synthetic mesh wrap devices for the creation of bioartificial myocardium and cardiowrap bioprostheses for ventricular support and myocardial repair ( Figure 5C) [69,70]. In advanced heart failure patients, having large dilated ventricles, complete cardiac wrapping is associated with bioprosthetic helical myocardial bands, that follow the anatomical heart configuration of native muscular ventricular bands ( Figure 5D).…”

Section: D Bioprinting Of Functional Myocardiummentioning

confidence: 99%

Recent Applications of Three Dimensional Printing in Cardiovascular Medicine

Gardin

Ferroni

Latrémouille

et al. 2020

Cells

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Three dimensional (3D) printing, which consists in the conversion of digital images into a 3D physical model, is a promising and versatile field that, over the last decade, has experienced a rapid development in medicine. Cardiovascular medicine, in particular, is one of the fastest growing area for medical 3D printing. In this review, we firstly describe the major steps and the most common technologies used in the 3D printing process, then we present current applications of 3D printing with relevance to the cardiovascular field. The technology is more frequently used for the creation of anatomical 3D models useful for teaching, training, and procedural planning of complex surgical cases, as well as for facilitating communication with patients and their families. However, the most attractive and novel application of 3D printing in the last years is bioprinting, which holds the great potential to solve the ever-increasing crisis of organ shortage. In this review, we then present some of the 3D bioprinting strategies used for fabricating fully functional cardiovascular tissues, including myocardium, heart tissue patches, and heart valves. The implications of 3D bioprinting in drug discovery, development, and delivery systems are also briefly discussed, in terms of in vitro cardiovascular drug toxicity. Finally, we describe some applications of 3D printing in the development and testing of cardiovascular medical devices, and the current regulatory frameworks that apply to manufacturing and commercialization of 3D printed products.Cells 2020, 9, 742 2 of 33 Cells 2020, 9, 742 3 of 33 in digital modeling softwares without the need for file type conversion [16]. Several medical image segmentation softwares are available; some of these are open-source and freely accessible, while others are commercial, licensed products. From the DICOM dataset, the target anatomic geometry is identified and segmented based on properties such as contrast or brightness [17]. As a result, segmentation masks are created such that pixels with the same intensity range are grouped and converted into 3D digital models using rendering techniques. These segmented digital models are then exported out in the standard tessellation language (STL) file type, which is the industry standard for 3D objects and 3D printing software [17]. Nevertheless, STL files do not contain color information and in order to print in multiple colors, a different file format will need to be used. For example, virtual reality modeling language (VRML) and additive manufacturing file format (AMF) provide multiple color and material options [18]. Once segmentation is completed, the final 3D digital model may be further modified within computer-aided design (CAD) software. The main post-processing adjustments of the 3D model are: Repairing errors and discontinuities that sometimes arise in the image segmentation and exporting processes, smoothing of the surface of the model due to scaling errors resulting from the resolution of the original medical image, and addition of other...

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ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure

Cited by 103 publications

References 151 publications

Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration

Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes

Recent Applications of Three Dimensional Printing in Cardiovascular Medicine

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