Self-assembly of these seeded cells with the aid of a biofriendly three-dimensional matrix results in the formation of functional tissue in short-term preclinical animal models ( 10, 14, 15). Decellularization of allogeneic or xenogeneic donor organs such as heart ( 9), liver ( 10), and lung ( 11, 12, 13) provides an acellular naturally occurring three-dimensional biologic scaffold material that subsequently can be seeded with either functional parenchymal cells or selected progenitor cell populations. In recent years a promising approach for functional organ replacement has emerged. A successful regenerative medicine strategy for whole-organ replacement would represent a quantum leap forward in the treatment of patients with end-stage organ disease. Whole-organ constructs such as heart, lung, and liver will require this type of immediate vascular supply. Although significant advances have been made in the development of engineered tissues such as blood vessels ( 4, 5), urinary bladder ( 6), and trachea ( 7, 8), none of these tissues require an intact vascular network that can be connected to the host circulation at the time of implantation. Those patients fortunate enough to receive an organ are burdened with the risk of chronic rejection and the morbidity associated with a lifelong regimen of immunosuppressant therapy. When one considers the additional patients who die waiting for heart or kidney transplants, the numbers become overwhelming. Approximately 27,000 deaths occur annually in the United States alone for patients with end-stage liver disease ( 1), 120,000 patients as a result of chronic lung disease ( 2), 112,000 from end-stage kidney failure ( 3), and 425,000 from coronary heart disease ( 4). However, the critical shortage of donor organs leads to increased morbidity and mortality for tens of thousands of patients each year. The definitive treatment for end-stage organ failure is orthotopic transplantation. Critical challenges and future directions are also discussed. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. However, significant challenges for three-dimensional organ engineering approach remain. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. However, the demand for transplantation far exceeds the number of available donor organs.
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