Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult

Silva, A.C.; Rodrigues, Silvia Cristina Martini; Caldeira, Joana; Nunes, Andreia; Sampaio-Pinto, Vasco; Resende, Tatiana P.; Oliveira, Maria José; Barbosa, Mário A.; Þorsteinsdóttir, Sólveig; Nascimento, Diana S.; Pinto-do-Ó, Perpétua

doi:10.1016/j.biomaterials.2016.06.062

Cited by 60 publications

(54 citation statements)

References 65 publications

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“…Our results showed that the residual DNA contents of sECM in PreST group were less than 50 ng/mg, which is similar to the criteria proposed by Crapo and colleagues [30]. Meanwhile, the collagen fibers of sECM presented typical transverse periodic striations [31] with an average diameter far less than 0.1 µm, which is similar to the diameter of cECM [4]. SECM in the present study showed a honeycomblike endomysium structure and perimysium fibers, which is similar to the microstructure of cECM [7].…”

Section: Discussionsupporting

confidence: 70%

“…Generally, researchers hold the opinion that both cECM and sECM have high biological compatibility. CECM has been proven to be suitable for the adhesion, proliferation, differentiation and maturity of Sca-l + cardiac progenitor cells [4], neonatal CMs [4] and human MSCs [32]. Studies showed that dog sECM supports the adhesion, survival of human vascular peripheral stem cells, NIH3T3 fibroblasts and human microvascular endothelial cells for at least 7 days, and promotes the differentiation of C2C12 myoblasts [16].…”

Section: Discussionmentioning

confidence: 99%

“…Generally, cECMs acquired by decellularization procedure are constituted of numerous of coiled and aligned fibril bundles and exhibit complex meshwork of pores [7]. Accumulated data have demonstrated that cECMs enhance the survival, proliferation, migration and cardiac differentiation of Sca-1 + [4] or c-kit + [8] cardiac progenitor cells. It also accelerates differentiation of human induced pluripotent stem cells (iPS) derived cardiovascular progenitor cells towards the cardiomyocytes (CMs), smooth muscle cells or endothelial cells [9], and promote the elongation and alignment of neonatal CMs [4, 10].…”

Section: Introductionmentioning

confidence: 99%

“…Concerning the capability to mimic native extracellular matrix (ECM) microenvironment, decellularized cardiac tissue has been considered as an attractive scaffold that preserves the architecture and biochemical composition of natural ECM [3, 4]. The main components of cardiac ECM (cECM) are collagens (type I, III and IV), fibronectin and laminin.…”

Section: Introductionmentioning

confidence: 99%

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Skeletal Extracellular Matrix Supports Cardiac Differentiation of Embryonic Stem Cells: a Potential Scaffold for Engineered Cardiac Tissue

Hong

Yin

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: Decellularized cardiac extracellular matrix (cECM) has been widely considered as an attractive scaffold for engineered cardiac tissue (ECT), however, its application is limited by immunogenicity and shortage of organ donation. Skeletal ECM (sECM) is readily available and shows similarities with cECM. Here we hypothesized that sECM might be an alternative scaffold for ECT strategies. Methods: Murine ventricular tissue and anterior tibial muscles were sectioned into 300 mm-thick, and then cECM and sECM were acquired by pretreatment/SDS/TritonX-100 three-step-method. Acellularity and morphological properties of ECM was assessed. SECM was recellularized with murine embryonic stem cells (mESCs) or mESC-derived cardiomyocytes (mESC-CMs), and was further studied by biocompatibility assessment, immunofluorescent staining, quantitative real-time PCR and electrophysiological experiment. Results: The relative residual contents of DNA, protein and RNA of sECM were comparable with cECM. The morphological properties and microstructure of sECM were similar to cECM. SECM supported mESCs to adhere, survive, proliferate and differentiate into functional cardiac microtissue with both electrical stimulated response and normal adrenergic response. Purified mESC-CMs also could adhere, survive, proliferate and form a sECM-based ECT with synchronized contraction within 6 days of recellularization. Conclusion: ECMs from murine skeletal muscle support survival and cardiac differentiation of mESCs, and are suitable to produce functional ECT patch. This study highlights the potential of patient specific of sECM to replace cECM for bioengineering ECT.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Skeletal Extracellular Matrix Supports Cardiac Differentiation of Embryonic Stem Cells: a Potential Scaffold for Engineered Cardiac Tissue

Hong

Yin

Sun

et al. 2018

Cell Physiol Biochem

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“…After reseeding with a cardiac progenitor cell line, the fetal dcECM showed greater cellular proliferation than the adult dcECM but no cardiac troponin was present in either scaffold. Higher levels of several factors involved in CM proliferation and improving cardiac repair, such as transforming growth factor-beta, periostin, fibronectin, and heparin-binding epidermal growth factor were present within the fetal dcECMs (Silva et al, 2016). Decellularized fetal (developmental day was not reported) and adult bovine myocardium's potential to improve hIPS-CM maturity was compared in another study.…”

Section: Natural Engineering In Vitro Approaches To Drive Cardiomyocymentioning

confidence: 99%

Naturally Engineered Maturation of Cardiomyocytes

Scuderi

Butcher

2017

Front. Cell Dev. Biol.

166

202

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Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte maturation. This information can then be utilized to develop natural engineering approaches that can emulate this fetal microenvironment and thus make prominent progress in pluripotent stem cell-derived maturity toward a more clinically relevant model for cardiac regeneration.

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Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration

Bejleri

Davis

2019

Adv Healthcare Materials

158

105

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Decellularized extracellular matrix (dECM) is a promising biomaterial for repairing cardiovascular tissue, as dECM most effectively captures the complex array of proteins, glycosaminoglycans, proteoglycans, and many other matrix components that are found in native tissue, providing ideal cues for regeneration and repair of damaged myocardium. dECM can be used in a variety of forms, such as solid scaffolds that maintain native matrix structure, or as soluble materials that can form injectable hydrogels for tissue repair. dECM has found recent success in many regeneration and repair therapies, such as for musculoskeletal, neural, and liver tissues. This review focuses on dECM in the context of cardiovascular applications, with variations in tissue and species sourcing, and specifically discusses advances in solid and soluble dECM development, in vitro studies, in vivo implementation, and clinical translation.

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Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult

Cited by 60 publications

References 65 publications

Skeletal Extracellular Matrix Supports Cardiac Differentiation of Embryonic Stem Cells: a Potential Scaffold for Engineered Cardiac Tissue

Skeletal Extracellular Matrix Supports Cardiac Differentiation of Embryonic Stem Cells: a Potential Scaffold for Engineered Cardiac Tissue

Naturally Engineered Maturation of Cardiomyocytes

Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration

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