scholarly journals Three-Dimensional Human Cardiac Tissue Engineered by Centrifugation of Stacked Cell Sheets and Cross-Sectional Observation of Its Synchronous Beatings by Optical Coherence Tomography

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yuji Haraguchi ◽  
Akiyuki Hasegawa ◽  
Katsuhisa Matsuura ◽  
Mari Kobayashi ◽  
Shin-ichi Iwana ◽  
...  

Three-dimensional (3D) tissues are engineered by stacking cell sheets, and these tissues have been applied in clinical regenerative therapies. The optimal fabrication technique of 3D human tissues and the real-time observation system for these tissues are important in tissue engineering, regenerative medicine, cardiac physiology, and the safety testing of candidate chemicals. In this study, for aiming the clinical application, 3D human cardiac tissues were rapidly fabricated by human induced pluripotent stem (iPS) cell-derived cardiac cell sheets with centrifugation, and the structures and beatings in the cardiac tissues were observed cross-sectionally and noninvasively by two optical coherence tomography (OCT) systems. The fabrication time was reduced to approximately one-quarter by centrifugation. The cross-sectional observation showed that multilayered cardiac cell sheets adhered tightly just after centrifugation. Additionally, the cross-sectional transmissions of beatings within multilayered human cardiac tissues were clearly detected by OCT. The observation showed the synchronous beatings of the thicker 3D human cardiac tissues, which were fabricated rapidly by cell sheet technology and centrifugation. The rapid tissue-fabrication technique and OCT technology will show a powerful potential in cardiac tissue engineering, regenerative medicine, and drug discovery research.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Katsuhisa Matsuura ◽  
Tatsuya Shimizu ◽  
Nobuhisa Hagiwara ◽  
Teruo Okano

We have developed an original scaffold-free tissue engineering approach, “cell sheet engineering”, and this technology has been already applied to regenerative medicine of various organs including heart. As the bioengineered three-dimensional cardiac tissue is expected to not only function for repairing the broad injured heart but also to be the practicable heart tissue models, we have developed the cell sheet-based perfusable bioengineered three-dimensional cardiac tissue. Recently we have also developed the unique suspension cultivation system for the high-efficient cardiac differentiation of human iPS cells. Fourteen-day culture with the serial treatments of suitable growth factors and a small compound in this stirring system with the suitable dissolved oxygen concentration produced robust embryoid bodies that showed the spontaneous beating and were mainly composed of cardiomyocytes (~80%). When these differentiated cells were cultured on temperature-responsive culture dishes after the enzymatic dissociation, the spontaneous and synchronous beating was observed accompanied with the intracellular calcium influx all over the area even after cell were detached from culture dishes as cell sheets by lowering the culture temperature. The cardiac cell sheets were mainly composed of cardiomyocytes (~80%) and partially mural cells (~20%). Furthermore, extracellular action potential propagation was observed between cell sheets when two cardiac cell sheets were partially overlaid, and this propagation was inhibited by the treatment with some anti-arrhythmic drugs. When the triple layered cardiac tissue was transplanted onto the subcutaneous tissue of nude rats, the spontaneous pulsation was observed over 2 months and engrafted cardiomyocytes were vascularized with the host tissue-derived endothelial cells. These findings suggest that cardiac cell sheets formed by hiPSC-derived cardiomyocytes might have sufficient properties for the creation of thickened cardiac tissue. Now we are developing the vascularized thickened human cardiac tissue by the repeated layering of cardiac cell sheets on the artificial vascular bed in vitro.


2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Akitoshi Inui ◽  
Hidekazu Sekine ◽  
Kazunori Sano ◽  
Izumi Dobashi ◽  
Azumi Yoshida ◽  
...  

The definitive treatment of severe heart failure is heart transplantation; however the number of heart transplantation procedures performed in Japan per year ranges from 30-40 due to donor shortage. Therefore, recently other treatments such as ventricular assist device or regenerative therapy by human cardiac tissue engineering have been developed and are considered as appropriate alternatives. We have developed an original technology, which was named cell-sheet based tissue engineering to fabricate functional three-dimensional tissue by layering cell sheets. The utilization of this technique allowed us to successfully engineer thick rat cardiac tissue with perfusable blood vessels in vitro. Here, we demonstrate a technique to engineer human cardiac tissue with perfusable blood vessels using cardiac cell sheets derived from human induced pluripotent stem cells, and porcine small intestine as a vascular bed for perfusion culture. The small intestine was harvested from with a branch of the superior mesenteric artery and vein and underwent mucosal resection after harvested tissue was cut open. To engineer cardiac tissue with perfusable blood vessels, cardiac cell sheets co-cultured with endothelial cells, were triple-layered and then was overlaid on the vascular bed in the bioreactor system. One day after perfusion culture, overlaid cardiac tissues pulsated spontaneously and were synchronized. The cardiac tissue construct was viable tissue without any observable necrosis. Furthermore we examined the possibility of transplantation of the in vitro engineered human cardiac tissue with the connectable host artery and vein. Engineered cardiac tissue was removed from the bioreactor system after 4-day perfusion, and transplanted to another pig heart. The branch of the superior mesenteric artery and vein of the graft were then reconnected to the host internal thoracic artery and vein. When the cardiac tissue reperfused, it began to beat spontaneously after a few minutes. We believe that this method is useful to fabricate functional cardiac tissue and may become an appropriate treatment for severe heart failure.


2010 ◽  
Vol 76 ◽  
pp. 114-124
Author(s):  
Seeram Ramakrishna ◽  
Jayarama Reddy Venugopal ◽  
Susan Liao

Attempts have been made to fabricate nanofibrous scaffolds to mimic the chemical composition and structural properties of extracellular matrix (ECM) for tissue/organ regeneration. Nanofibers with various patterns have been successfully produced from synthetic and natural polymers through a relatively simple technique of electrospinning. The resulting patterns can mimic some of the diverse tissue-specific orientation and three-dimensional (3D) fibrous structure. Studies on cell-nanofiber interactions have revealed the importance of nanotopography on cell adhesion, proliferation and differentiation. Our recent data showed that hematopoietic stem cells (HSCs) as well as mesenchymal stem cells (MSCs) can rapidly and effectively attached to the functionalized nanofibers. Mineralized 3D nanofibrous scaffold with bone marrow derived MSCs has been applied for bone tissue engineering. The use of injectable nanofibers for cardiac tissue engineering applications is attractive as they allow for the encapsulation of cardiomyocytes/MSCs as well as bioactive molecules for the repair of myocardial infarction. Duplicate 3D heart helix microstructure by the nanofibrous cardiac patch might provide functional support for infarcted myocardium. Furthermore, clinical applications of electrospun nanofibers for regenerative medicine are highly feasible due to the ease and flexibility of fabrication with the cost-effective method of making nanofibers.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1038
Author(s):  
Sonia Trombino ◽  
Federica Curcio ◽  
Roberta Cassano ◽  
Manuela Curcio ◽  
Giuseppe Cirillo ◽  
...  

Cardiac regeneration aims to reconstruct the heart contractile mass, preventing the organ from a progressive functional deterioration, by delivering pro-regenerative cells, drugs, or growth factors to the site of injury. In recent years, scientific research focused the attention on tissue engineering for the regeneration of cardiac infarct tissue, and biomaterials able to anatomically and physiologically adapt to the heart muscle have been proposed as valuable tools for this purpose, providing the cells with the stimuli necessary to initiate a complete regenerative process. An ideal biomaterial for cardiac tissue regeneration should have a positive influence on the biomechanical, biochemical, and biological properties of tissues and cells; perfectly reflect the morphology and functionality of the native myocardium; and be mechanically stable, with a suitable thickness. Among others, engineered hydrogels, three-dimensional polymeric systems made from synthetic and natural biomaterials, have attracted much interest for cardiac post-infarction therapy. In addition, biocompatible nanosystems, and polymeric nanoparticles in particular, have been explored in preclinical studies as drug delivery and tissue engineering platforms for the treatment of cardiovascular diseases. This review focused on the most employed natural and synthetic biomaterials in cardiac regeneration, paying particular attention to the contribution of Italian research groups in this field, the fabrication techniques, and the current status of the clinical trials.


2021 ◽  
Vol 2021 ◽  
pp. 1-20 ◽  
Author(s):  
Dhinakaran Veeman ◽  
M. Swapna Sai ◽  
P. Sureshkumar ◽  
T. Jagadeesha ◽  
L. Natrayan ◽  
...  

As a technique of producing fabric engineering scaffolds, three-dimensional (3D) printing has tremendous possibilities. 3D printing applications are restricted to a wide range of biomaterials in the field of regenerative medicine and tissue engineering. Due to their biocompatibility, bioactiveness, and biodegradability, biopolymers such as collagen, alginate, silk fibroin, chitosan, alginate, cellulose, and starch are used in a variety of fields, including the food, biomedical, regeneration, agriculture, packaging, and pharmaceutical industries. The benefits of producing 3D-printed scaffolds are many, including the capacity to produce complicated geometries, porosity, and multicell coculture and to take growth factors into account. In particular, the additional production of biopolymers offers new options to produce 3D structures and materials with specialised patterns and properties. In the realm of tissue engineering and regenerative medicine (TERM), important progress has been accomplished; now, several state-of-the-art techniques are used to produce porous scaffolds for organ or tissue regeneration to be suited for tissue technology. Natural biopolymeric materials are often better suited for designing and manufacturing healing equipment than temporary implants and tissue regeneration materials owing to its appropriate properties and biocompatibility. The review focuses on the additive manufacturing of biopolymers with significant changes, advancements, trends, and developments in regenerative medicine and tissue engineering with potential applications.


Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5795
Author(s):  
Adam Chyzy ◽  
Marta E. Plonska-Brzezinska

Hydrogels (HGs), as three-dimensional structures, are widely used in modern medicine, including regenerative medicine. The use of HGs in wound treatment and tissue engineering is a rapidly developing sector of medicine. The unique properties of HGs allow researchers to easily modify them to maximize their potential. Herein, we describe the physicochemical properties of HGs, which determine their subsequent applications in regenerative medicine and tissue engineering. Examples of chemical modifications of HGs and their applications are described based on the latest scientific reports.


2006 ◽  
Vol 41 (4) ◽  
pp. 742-742
Author(s):  
A.N. Morritt ◽  
R.J. Dilley ◽  
J. Rickards ◽  
X.L. Han ◽  
D. McCombe ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Claudio Muscari ◽  
Emanuele Giordano ◽  
Francesca Bonafè ◽  
Marco Govoni ◽  
Carlo Guarnieri

The production of a functional cardiac tissue to be transplanted in the injured area of the infarcted myocardium represents a challenge for regenerative medicine. Most cell-based grafts are unviable because of inadequate perfusion; therefore, prevascularization might be a suitable approach for myocardial tissue engineering. To this aim, cells with a differentiation potential towards vascular and cardiac muscle phenotypes have been cocultured in 2D or 3D appropriate scaffolds. In addition to these basic approaches, more sophisticated strategies have been followed employing mixed-cell sheets, microvascular modules, and inosculation from vascular explants. Technologies exerting spatial control of vascular cells, such as topographical surface roughening and ordered patterning, represent other ways to drive scaffold vascularization. Finally, microfluidic devices and bioreactors exerting mechanical stress have also been employed for high-throughput scaling-up production in order to accelerate muscle differentiation and speeding the endothelialization process. Future research should address issues such as how to optimize cells, biomaterials, and biochemical components to improve the vascular integration of the construct within the cardiac wall, satisfying the metabolic and functional needs of the myocardial tissue.


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