日本語 The Cardiac Tube Group
Fabrication of Bioartificial Pump using Cell Sheet-based Tissue Engineering
Tissue engineering approaches involving the direct transplantation of cardiac patches has received significant attention as an alternative method for the treatment of damaged hearts. In contrast, we used cardiac cell sheets harvested from temperature-responsive dishes to create pulsatile cardiac tubes as organ-like structures and examined both in vitro and in vivo function. (Fig.1)
As a result, in vitro fabricated beating cardiac tube showed spontaneously synchronized pulsations in macroscopic levels. Additionally, the cardiac tubes presented measurable inner pressure changes evoked in response to the spontaneous tube contraction. Furthermore, we fabricated an implantable tube-shaped myocardial tissue by wrapping neonatal rat cardiac cell sheet around a resected adult rat thoracic aorta, and transplanted in the abdominal aorta of athymic rats. Four weeks after transplantation, the myocardial tubes demonstrated spontaneous and synchronous pulsations independent of the host heartbeat. Independent graft pressures with a magnitude of 5.9±1.7mmHg due to their independent pulsations were also observed. Histological study and transmission electron microscopy indicated that the beating tubes were composed of cardiac tissues that resemble the native heart. Additionally, Histological examination demonstrated the presence of endothelial cells and typical blood vessels within the myocardial tubes. Furthermore, it was revealed that the myocardial tubes were nourished with branch of the aorta. Finally, when myocardial tubes used for aortic replacement were compared to grafts implanted in the abdominal cavity, significantly increased tissue thickness, as well as expression of brain natiuretic peptide, α-myosin heavy chain, and β-myosin heavy chain, suggested that pulsation due to host blood flow within the lumen of the myocardial tubes has a profound effect on stimulating cardiomyocyte hypertrophy and growth. These results demonstrate the next step of myocardial tissue reconstruction and a shift towards the fabrication of independently-functioning cardiac structures having a potential for acting as tissue engineered cardiac assist devices.
Currently, in order to further enhancement of myocardial contraction, we are trying to create possess controlled cellular arrangements of cardiomyocytes using micropaterned temperature-responsive culture surfaces. (Fig.2)
Fig.1：
Creation of 3D tubular myocardial tissue that acts like a cardioassist pump
←Click to enlarge
Fig.2：
An attempt to produce myocardial tube tissue processed to have an orientation property
←Click to enlarge
Researcher Introduction
Institute of Advanced BioMedical Engineering and Science,
Assistant Professor Hidekazu SEKINE
Although these challenges have been performed only in small scale, the future solutions for scaling up problems give more powerful construct creation, resulting in the developments of remarkable tissue engineered cardiac assist devices or organ replacement. Overall, cell sheet-based tissue engineering should have enormous potential in myocardial tissue regenerative medicine and rescue many patients suffering severe heart failure. In addition to clinical use, pulsatile myocardial tube constructs should be also useful for future applications in physiological studies and pharmacological screening.
Achievements
- Kubo H, Shimizu T, Yamato M, Fujimoto T, Okano T. Creation of myocardial tubes using cardiomyocyte sheets and an in vitro cell sheet-wrapping device. Biomaterials. 2007;28:3508 -16.
- Sekine H, Shimizu T, Yang J, Kobayashi E, Okano T. Pulsatile myocardial tubes fabricated with cell sheet engineering. Circulation. 2006;114:I87- 93.
