Application of a Fresh Decellularized Pulmonary Allograft for Pulmonary Valve Replacement in Japan

Abstract

Background: Tissue engineering has advanced the technique of decellularization of the heart valve. The valve is reseeded with the patient's own cells after implantation with suppression of immunologic reactions. The same advantage has been reported for fresh decellularized heart valves, and more than 10 years of excellent outcomes have been achieved. We began performing such heart valve implantations in 2013 as part of a clinical study at Osaka University. We report our evaluation of the safety and efficacy of heart valve implantation. Methods and Results:Human pulmonary valves from the German Society for Tissue Transplantation (n=2) or from Japanese heart transplant recipient heart (n=4) were used to make decellularized heart valves; the decellularization process was the same as that used in Europe. Valves were implanted in 5 adults with pulmonary valve insufficiency after tetralogy of Fallot repair and in 1 infant with a double-outlet right ventricle with pulmonary stenosis. Postoperative echocardiography and cardiac magnetic resonance imaging revealed that the valve and ventricular function were significantly improved and maintained postoperatively. Conclusions:Decellularized heart valves could be the new material used as artificial heart valves. Pulmonary allografts derived from the hearts of heart transplant recipients are considered to be useful material for decellularized heart valves. The application of this valve to Japanese clinical circumstances and using the hearts of heart transplant recipients is considered to be very significant.

Decellularized Extracellular Matrix-based Bioinks for Engineering Tissue- and Organ-specific Microenvironments

“…Cardiac tissue-derived dECM-based hydrogels with preserved bioactivity demonstrated enhanced potential for in vitro and in vivo applications for cardiac regeneration . Similarly, decellularized heart slices with preserved protein components and tissue architecture were obtained, which, upon mechanical evaluation, showed similar characteristics to a native tissue. ,, From the perspective of improving the therapeutic treatment for valvular heart disease, human heart valves (aortic heart valve, pulmonary heart valve, or both) were decellularized. − However, the decellularized and bioengineered heart valve should provide a sufficient and immediate mechanical function upon implantation to ensure patient’s survival. Hence, for successful clinical applications, the heart valve substitute is required to mimic and preserve both the functional and mechanical properties of the native tissue.…”

Tissue-Engineered Grafts from Human Decellularized Extracellular Matrices: A Systematic Review and Future Perspectives

“…Thus, the fabrication of human decellularized heart valve scaffolds seeded with autologous cells prior to implantation or recolonized in vivo after surgery represents a concept for improving current valvular heart disease therapy. In the last two decades, human heart valve allografts have been prepared by decellularization of the aortic heart valve [59,162,163,164,165], the pulmonary heart valve [57,69,166,167], or both [168,169,170,171,172]. In particular, heart valves were taken from cadavers [168], procured from a tissue banking facility [164,167,169,172], removed from the heart of the recipient during transplantation surgery [166,69], or obtained from nonheartbeating [165] and heartbeating [162] organ donors.…”

“…In the perspective of engineered valve fabrication, the decellularization process plays a crucial role for its impact on ECM composition and architecture, which need to remain unchanged. According to the literature, detergents [58,61,63,65,66,67,69,163,171], enzymes [57,59,60,62,64,68,162,168,169], or both [164,165,166,167,170,172] have been used in various combinations and concentrations to achieve cell-free valve scaffolds with preserved ECM (Table 5). The marked reduction of class I and class II major histocompatibility complex expression following decellularization suggests the lowered antigenicity of valve leaflets in the perspective of in vivo implantation [57,172].…”

“…In particular, aortic valve allografts were succeffully tested for aortic root replacement in the presence of congenital or acquired aortic valve disease, aortic aneurysm with aortic valve disease, or native or prosthetic aortic valve endocarditis [59,63,66]. Pulmonary allografts have been employed in the replacement of the pulmonary valve for right ventricular outflow tract (RVOT) reconstruction during Ross operation [57,58,61,64] or for the treatment of pulmonary dysfunctions [57,61,62,65,67,68,69]. Remarkably, the implantation of acellular allografts did not provoke a panel reactive antibody (PRA) response, which proved to stimulate the host recellularization of the matrix and significantly improve valve and ventricular function.…”

Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?

“…Unseeded 3 y 47 -P [ 69] No mention Allograft Human ESPOIR Unseeded 3 y 6 cases -P [ 115] No mention homograft Human Chemical At room temperature, tissues were treated with 0.5% SDC and 0.5% SDS for 36 h. Finally, Tissues were washed with NaCl 0.9% solution and stored at 4°C unseeded 10 y -P [ 83] DOA deoxycholic acid, SDS sodium dodecyl sulfate, EDTA ethylenediaminetetraacetic acid, RNAse ribonuclease, DNase deoxyribonuclease, EtOH Ethanol, PEG polyethylene glycol…”