Engineered liver for transplantation
Introduction
Orthotopic liver transplantation is the only definitive treatment option for end stage liver failure which causes 27 000 deaths annually in the US. The recent advances in surgical techniques and immunosuppression therapies have resulted in a decreasing trend in mortality rates of patients after receiving a transplant over the last two decades. Unfortunately, the shortage of donor organs remains the primary limiting factor in transplanting more patients on the organ waiting list [1]. There are about 17 000 patients on the waiting list and only about 6000 patients receive transplants each year [2]. Moreover, the increased incidence of hepatitis C infection and obesity-driven fatty liver disease will likely reduce the number of donor organs suitable for transplantation [3]. Strategies to develop alternative treatment options are continuously being investigated. One approach involves the engineering of liver tissue to fill the gap of insufficient numbers of donor organs for transplantation. This effort which is termed ‘tissue engineering’ is an interdisciplinary field that integrates engineering and life sciences to create functional tissue constructs with the aim of replacing the failing organ or tissue. In its simplest conceptual form, the effort involves seeding and cultivation of cells in a three dimensional structure made of synthetic and/or biological polymer materials that provide physical support and biological cues to support cell growth and function. Despite decades of work, the only tissue engineered products that made the transition to clinic are limited to non-cellular tissues and tissues that function in a mostly mechanical/structural mode such as the skin, cartilage, and bladder [4]. Other organs, like liver, have been difficult to fabricate using traditional tissue engineering approaches, partly due to the lack of a well-defined circulatory network in the scaffold to maintain the cells that are within. A novel technique, whole-organ decellularization, has evolved to address this drawback in current scaffold preparation methods. This technique, first demonstrated for the heart [5•] and quickly adopted for the liver [6••], retains the circulatory network of the native organ, allowing for the construct to be connected to the blood torrent upon transplantation. Here, we will provide a review of the area of hepatic tissue engineering for the creation of a transplantable liver substitute. We will address the key challenges in whole liver tissue engineering such as cell seeding, blood compatibility, source of cells and scaffolds, and immunological issues.
Section snippets
Hepatic tissue engineering
Hepatocyte transplantation has been investigated as a feasible alternative to orthotopic liver transplantation to treat liver-based inborn errors of metabolism where the goal is to replace a single deficient enzyme or its product [7•]. In these cases, there is the intact hepatic primary function and architecture, and the transplantation of a hepatocyte mass equivalent to 10% of the patient's liver is sufficient to normalize liver function [8]. Hepatocyte transplantation involves transfer of
Whole liver engineering
In recent years, a novel technique for the preparation of whole organ scaffolds has emerged in tissue engineering (Figure 1). The technique involves perfusion decellularization of cadaveric organs to generate extracellular matrix scaffolds that retain the gross morphology and vascular architecture of the native organ [33••]. The scaffold is then repopulated with parenchymal and/or non-parenchymal cells by either direct injection into the parenchyma or perfusion through the vasculature. The
Conclusion
Since the advent of the field of tissue engineering, the progress in liver tissue engineering has been limited by the challenge of finding the right scaffold material and architecture to facilitate hepatocyte function and survival in vivo. Whole liver scaffolds prepared by perfusion decellularization of cadaveric organs circumvent these issues and present as a promising platform to engineer livers for transplantation. However, the task is complex and challenging and requires approaches from
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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