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cardiac tissue engineering

Hung X Nguyen, Robert D Kirkton, Nenad Bursac
The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes...
October 18, 2016: Nature Communications
Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUNDS: -Tissue engineering enables the generation of functional human cardiac tissue using cells derived in vitro in combination with biocompatible materials. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electrical pacing on the maturation of hiPSC-derived cardiac tissues. METHODSS: -Cardiomyocytes derived from hiPSCs were used to generate collagen-based bioengineered human cardiac tissue...
October 13, 2016: Circulation
Maurizio Pesce, Elisa Messina, Isotta Chimenti, Antonio Paolo Beltrami
The life-long story of the heart starts concomitantly with primary differentiation events occurring in multipotent progenitors located in the so called heart tube. This initially tubular structure starts a looping process which leads to formation of the final four chambered heart with a primary contribution of geometric and position-associated cell sensing. While this establishes the correct patterning of the final cardiac structure, it also feedbacks to fundamental cellular machineries controlling proliferation and differentiation, thus ensuring a coordinated restriction of cell growth and a myocyte terminal differentiation...
October 13, 2016: Stem Cells and Development
Christopher P Jackman, Aaron L Carlson, Nenad Bursac
Engineered cardiac tissues hold promise for cell therapy and drug development, but exhibit inadequate function and maturity. In this study, we sought to significantly improve the function and maturation of rat and human engineered cardiac tissues. We developed dynamic, free-floating culture conditions for engineering "cardiobundles", 3-dimensional cylindrical tissues made from neonatal rat cardiomyocytes or human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) embedded in fibrin-based hydrogel. Compared to static culture, 2-week dynamic culture of neonatal rat cardiobundles significantly increased expression of sarcomeric proteins, cardiomyocyte size (∼2...
December 2016: Biomaterials
Yi Li, Xiaoli Shi, Lei Tian, Hongyu Sun, Yujing Wu, Xia Li, Jianjun Li, Yujie Wei, Xinxiao Han, Jiao Zhang, Xiaowei Jia, Rui Bai, Limin Jing, Peng Ding, Huiliang Liu, Dong Han
A schematic for the mechanism of accelerating the assembly of intercalated discs (IDs) in cardiac myocytes regulated by gold nanoparticles (AuNPs) is presented. AuNPs with local nanoscale stiffness in the substrate activate β1-integrin signaling, which mediates the activation of integrin-linked kinase (ILK) and its downstream signal kinase by stimulating expression of the transcription factors GATA4 and MEF-2c.
October 10, 2016: Advanced Materials
Anna Mallone, Benedikt Weber, Simon P Hoerstrup
In the effort of improving treatment for cardiovascular disease (CVD), scientists struggle with the lack of the regenerative capacities of finally differentiated cardiovascular tissues. In this context, the advancements in regenerative medicine contributed to the development of cell-based therapies as well as macro- and micro-scale tissue-engineering technologies. The current experimental approaches focus on different regenerative strategies including a broad spectrum of techniques such as paracrine-based stimulation of autologous cardiac stem cells, mesenchymal cell injections, 3D microtissue culture techniques and vascular tissue-engineering methods...
July 2016: Transfusion Medicine and Hemotherapy
Ngoc Thien Lam, Timothy J Muldoon, Kyle P Quinn, Narasimhan Rajaram, Kartik Balachandran
The role of valvular interstitial cell (VIC) architecture in regulating cardiac valve function and pathology is not well understood. VICs are known to be more elongated in a hypertensive environment compared to those in a normotensive environment. We have previously reported that valve tissues cultured under hypertensive conditions are prone to acute pathological alterations in cell phenotype and contractility. We therefore aimed to rigorously study the relationship between VIC shape, contractile output and other functional indicators of VIC pathology...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Yu Shrike Zhang, Andrea Arneri, Simone Bersini, Su-Ryon Shin, Kai Zhu, Zahra Goli-Malekabadi, Julio Aleman, Cristina Colosi, Fabio Busignani, Valeria Dell'Erba, Colin Bishop, Thomas Shupe, Danilo Demarchi, Matteo Moretti, Marco Rasponi, Mehmet Remzi Dokmeci, Anthony Atala, Ali Khademhosseini
Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium...
December 2016: Biomaterials
Li Wang, Xiaoqing Zhang, Cong Xu, Hui Liu, Jianhua Qin
Human induced pluripotent stem cells (hiPSCs) and appropriate scaffolds are of great interest in cardiac tissue engineering. In this work, we present a simple and new strategy to produce a thin collagen membrane with a natural microstructure from porcine tendons and reconstruct the functional cardiac tissues by recellularizing hiPSC-derived cardiomyocytes onto the membrane, for the first time. The collagen membrane maintained its intact properties after decellularization, the composition of which was identified as collagen I...
October 18, 2016: Biomaterials Science
Akansha Pandey, Vishakha Swarnkar, Tushar Pandey, Piush Srivastava, Sanjeev Kanojiya, Dipak Kumar Mishra, Vineeta Tripathi
Calotropis procera is a medicinal plant of immense importance due to its pharmaceutical active components, especially cardiac glycosides (CG). As genomic resources for this plant are limited, the genes involved in CG biosynthetic pathway remain largely unknown till date. Our study on stage and tissue specific metabolite accumulation showed that CG's were maximally accumulated in stems of 3 month old seedlings. De novo transcriptome sequencing of same was done using high throughput Illumina HiSeq platform generating 44074 unigenes with average mean length of 1785 base pair...
October 5, 2016: Scientific Reports
Kwaku Dad Abu-Bonsrah, Dongcheng Zhang, Donald F Newgreen
Chickens are an invaluable model for studying human diseases, physiology and especially development, but have lagged in genetic applications. With the advent of Programmable Engineered Nucleases, genetic manipulation has become efficient, specific and rapid. Here, we show that the CRISPR/Cas9 system can precisely edit the chicken genome. We generated HIRA, TYRP1, DICER, MBD3, EZH2, and 6 other gene knockouts in two chicken cell lines using the CRISPR/Cas9 system, with no off-target effects detected. We also showed that very large deletions (>75 kb) could be achieved...
October 3, 2016: Scientific Reports
Gordana Vunjak-Novakovic
Tissue-engineered regeneration of a failing human heart remains a major challenge, while cardiovascular disease continues to take more lives than all cancers combined. Much has been learned from the basic and clinical studies, with the most interesting developments happening at the interfaces of disciplines. This seems to be the right time to step back and rethink the evolving paradigm of tissue engineering, and to reflect about the most promising directions to take. We clearly need new therapeutic modalities that are effective and yet simple enough to be practical, and the field is looking into the therapeutic potential of stem-progenitor cells, cardiac and vascular, that are enabled by bioactive factors and functionalized biomaterials...
September 6, 2016: Journal of Thoracic and Cardiovascular Surgery
Andrea V Bagdadi, Maryam Safari, Prachi Dubey, Pooja Basnett, Panagiotis Sofokleous, Eleanor Humphrey, Ian Locke, Mohan Edirisinghe, Cesare Terracciano, Aldo R Boccaccini, Jonathan C Knowles, Sian E Harding, Ipsita Roy
Cardiac tissue engineering (CTE) is currently a prime focus of research due to an enormous clinical need. In this work, a novel functional material, Poly(3-hydroxyoctanoate), P(3HO), a medium chain length polyhydroxyalkanoate (PHA), produced using bacterial fermentation, was studied as a new potential material for CTE. Engineered constructs with improved mechanical properties, crucial for supporting the organ during new tissue regeneration, and enhanced surface topography, to allow efficient cell adhesion and proliferation, were fabricated...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Aida Llucià-Valldeperas, Carolina Soler-Botija, Carolina Gálvez-Montón, Santiago Roura, Cristina Prat-Vidal, Isaac Perea-Gil, Benjamin Sanchez, Ramon Bragos, Gordana Vunjak-Novakovic, Antoni Bayes-Genis
: : Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue-engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time...
September 29, 2016: Stem Cells Translational Medicine
Tze-Wen Chung, Hsin-Yu Lo, Tzung-Han Chou, Jan-Hou Chen, Shoei-Shen Wang
Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(ε-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF-PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces...
September 28, 2016: Macromolecular Bioscience
Wendy Keung, Lihuan Ren, Sen Li, Andy On-Tik Wong, Anant Chopra, Chi-Wing Kong, Gordon F Tomaselli, Christopher S Chen, Ronald A Li
Human embryonic stem cells (hESCs) is a potential unlimited ex vivo source of ventricular (V) cardiomyocytes (CMs), but hESC-VCMs and their engineered tissues display immature traits. In adult VCMs, sarcolemmal (sarc) and mitochondrial (mito) ATP-sensitive potassium (KATP) channels play crucial roles in excitability and cardioprotection. In this study, we aim to investigate the biological roles and use of sarcKATP and mitoKATP in hESC-VCM. We showed that SarcIK, ATP in single hESC-VCMs was dormant under baseline conditions, but became markedly activated by cyanide (CN) or the known opener P1075 with a current density that was ~8-fold smaller than adult; These effects were reversible upon washout or the addition of GLI or HMR1098...
September 28, 2016: Scientific Reports
Sonia Ortiz-Miranda, Rui Ji, Agata Jurczyk, Ken-Edwin Aryee, Shunyan Mo, Terry Fletcher, Scott A Shaffer, Dale L Greiner, Rita Bortell, Ronald Gregg, Alan Cheng, Leah J Hennings, Ann R Rittenhouse
Knockout technology has proven useful for delineating functional roles of specific genes. Here we describe and provide an explanation for striking pathology that occurs in a subset of genetically engineered mice expressing a rat CaVβ2a transgene under control of the cardiac α-myosin heavy chain promoter. Lesions were limited to mice homozygous for transgene and independent of native Cacnb2 genomic copy number. Gross findings included an atrophied pancreas, decreased adipose tissue, thickened, orange intestines, and enlarged liver, spleen and abdominal lymph nodes...
September 22, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Hidetoshi Masumoto, Jun K Yamashita
Stem cell therapy is a promising therapeutic option for severe cardiac diseases that are resistant to conventional therapies. To overcome the unsatisfactory results of most clinical researches on stem cell injections to an injured heart, we are developing bioengineered cardiac tissue grafts using pluripotent stem cell-derived cardiomyocytes and vascular cells. We have validated the functional benefits of mouse embryonic stem cell-derived and human induced pluripotent stem cell-derived cardiac tissue sheets (CTSs) in a rat myocardial infarction model...
November 2016: Current Treatment Options in Cardiovascular Medicine
Akiko Tanaka, Keigo Kawaji, Amit R Patel, Takeyoshi Ota
OBJECTIVES: An extracellular matrix patch was implanted in the porcine right ventricle for in situ myocardial regeneration. A newly developed cardiovascular magnetic resonance protocol was utilized to investigate the regional physio-mechanical function of the patch. METHODS: Cardiovascular magnetic resonance was performed at 60-day after the porcine right ventricular wall full thickness substitution with an extracellular matrix cardiac patch (n = 5). Dacron patches and remote normal right ventricle served as control (n = 5/each)...
September 13, 2016: Interactive Cardiovascular and Thoracic Surgery
Nancy K Drew, Nicholas E Johnsen, Jason Q Core, Anna Grosberg
In a properly contracting cardiac muscle, many different constructs are organized into an intricate architecture. While it has been observed that this organization is altered in pathological conditions, the relationship between length-scales and architecture has not been properly explored. In this work, we utilize a variety of architecture metrics to quantify organization and consistency of single constructs over multiple scales as well as correlation of organization of multiple constructs. Specifically, as the best way to characterize cardiac tissues, we chose the orientational and co-orientational order parameters...
September 12, 2016: Journal of Biomechanical Engineering
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