Strategies and Processes to Decellularize and Recellularize Hearts to Generate Functional Organs and Reduce the Risk of Thrombosis

Abstract

Heart failure is one of the leading causes of death in the United States. Current therapies, such as heart transplants and bioartificial hearts, are helpful, but not optimal. Decellularization of porcine whole hearts followed by recellularization with patient-specific human cells may provide the ultimate solution for patients with heart failure. Great progress has been made in the development of efficient processes for decellularization, and the design of automated bioreactors. Challenges remain in selecting and culturing cells, growing the cells on the decellularized scaffolds without contamination, characterizing the regenerated organs, and preventing thrombosis. Various strategies have been proposed to prevent thrombosis of blood-contacting devices, including reendothelization and the creation of nonfouling surfaces using surface modification technologies. This review discusses the progress and remaining challenges involved with recellularizing whole hearts, focusing on the prevention of thrombosis.

Advancing biomaterials of human origin for tissue engineering

“…Thus far, ECM and cells procured from the above-mentioned tissues and organs have been used to study the potential advantage of tissue specificity in maintaining selected cell functions and phenotypes, and these ECMs have been demonstrated to affect cell chemotaxis and mitogenesis, to guide cell differentiation and to induce constructive host tissue remodeling responses. The 3D ultrastructure, composition and surface topology of the organ ECM all likely contribute to these effects [284,476,552]. In contrast, the remaining residual cellular material within the biological scaffold materials attenuates or fully negates the constructive tissue remodeling advantages in vivo .…”

<b>Development of equipment for decellularization using the perfusion method

“…Decellularization tests with chicken hearts demonstrated the proper functioning of the equipment and allowed visual monitoring to ensure complete organ decellularization. While developing the equipment, we considered the possibility of its adaptation for use in various published protocols (Akhyari et al, 2011;Momtahan, Sukavaneshvar, Roeder, & Cook, 2014;Gilbert, Sellaro, & Badylak, 2006;Ott et al, 2008). To achieve perfusion, it is essential to assess which method best fits the organ utilized.…”

“…Constant pressure control was used in previous studies (Weymann et al, 2011;Sierad et al, 2015) and can be achieved by adding a controller and a pressure transducer to the system. Several recent publications (Sierad et al, 2015;Momtahan et al, 2014) evaluated the advantages of performing constant-pressure perfusions for decellularization. However, the present study used constant flow control, and the pressure was monitored by a pressure gauge without controlling the rotation as a function of the pressure.…”

Using Hemolysis as a Novel Method for Assessment of Cytotoxicity and Blood Compatibility of Decellularized Heart Tissues

“…Acellular ECM can be obtained by decellularization of native tissue either by perfusing detergent solutions through the vasculature or diffusion of this solution through pieces of tissue. 28 Decellularization removes any cellular materials from the matrix that might cause immune reaction after transplantation.…”

“…This method would also reduce the need for antirejection medications posttransplant, normally used to suppress the immune response to the transplanted organ. 2 To achieve success, it is necessary to obtain very pure cECM samples that will be able to support cell growth without any cytotoxic effects. It is crucial to develop decellularization techniques that produce intact cECM for cardiac tissue engineering and to learn more about the biology of cECM to take advantage of cECM molecules that result in a better recruitment of the cells.…”