Cardiac muscle tissue engineering: toward an  in vitro model for electrophysiological studies

Bursac, Nenad; Papadaki, Maria; Cohen, Richard J.; Schoen, Frederick J.; Eisenberg, S.R.; Carrier, Rebecca L.; Vunjak‐Novakovic, Gordana; Freed, Lisa E.

doi:10.1152/ajpheart.1999.277.2.h433

Cited by 268 publications

(247 citation statements)

References 36 publications

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“…When attached the typical cell size range was 50-70 lm. mTERT-MSCs were seeded on relatively thin scaffold, limited to 100-200 lm thickness (rather than millimeters as in other works, for example [19]), following literature indications for soft tissue applications [9,39,40]. …”

Section: Cell Culturementioning

confidence: 99%

Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning

et al. 2010

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a b s t r a c tA novel (scalable) electrospinning process was developed to fabricate bio-inspired multiscale threedimensional scaffolds endowed with a controlled multimodal distribution of fiber diameters and geared towards soft tissue engineering. The resulting materials finely mingle nano-and microscale fibers together, rather than simply juxtaposing them, as is commonly found in the literature. A detailed proof of concept study was conducted on a simpler bimodal poly(e-caprolactone) (PCL) scaffold with modes of fiber distribution at 600 nm and 3.3 lm. Three conventional unimodal scaffolds with mean diameters of 300 nm and 2.6 and 5.2 lm, respectively, were used as controls to evaluate the new materials. Characterization of the microstructure (i.e. porosity, fiber distribution and pore structure) and mechanical properties (i.e. stiffness, strength and failure mode) indicated that the multimodal scaffold had superior mechanical properties (Young's modulus $40 MPa and strength $1 MPa) in comparison with the controls, despite the large porosity ($90% on average). A biological assessment was conducted with bone marrow stromal cell type (mesenchymal stem cells, mTERT-MSCs). While the new material compared favorably with the controls with respect to cell viability (on the outer surface), it outperformed them in terms of cell colonization within the scaffold. The latter result, which could neither be practically achieved in the controls nor expected based on current models of pore size distribution, demonstrated the greater openness of the pore structure of the bimodal material, which remarkably did not come at the expense of its mechanical properties. Furthermore, nanofibers were seen to form a nanoweb bridging across neighboring microfibers, which boosted cell motility and survival. Lastly, standard adipogenic and osteogenic differentiation tests served to demonstrate that the new scaffold did not hinder the multilineage potential of stem cells.

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Section: Cell Culturementioning

confidence: 99%

Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning

et al. 2010

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“…Three-dimensional cardiac tissue constructs that express structural and physiological features characteristic of native cardiac muscle have been engineered in vitro using fetal or neonatal rat cardiac myocytes (CMs) on collagen fibers 2 , fibrous polyglycolic acid scaffolds [3][4][5][6][7] and porous collagen scaffolds [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

“…In early studies, cells were seeded onto scaffolds and cultivated in dishes 4,7,8,11 , in spinner flasks 3,4,7 or in rotating vessels 2,4,7 . Inallof these systems, oxygen dissolved in culture medium was transported to the cells by molecular diffusion.…”

Section: Introductionmentioning

confidence: 99%

Cardiac tissue engineering using perfusion bioreactor systems

et al. 2008

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This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is 'biomimetic' in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2-4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and highfidelity models for biological research.

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“…1999; Santacruz et al. 2015) following protocols approved by the Institutional Animal Care and Use Committees at Duke University, Harvard Medical School and Brigham Women's Hospital.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation

et al. 2017

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Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m. Pharmacological activation of AMP‐activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF‐1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF‐1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia.

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Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies

Cited by 268 publications

References 36 publications

Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning

Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning

Cardiac tissue engineering using perfusion bioreactor systems

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation

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