Chapter 7 - Transplantation of engineered cells and tissues

Abstract

Experience with allogeneic, tissue-engineered, skin tissues and organs indicate that, in contrast to organs transplantation from patients, they elicit little immune response. Experiments show the persistence of grafts and the reduced responses of patients both in terms of cellular and humoral systems. These properties are related to the major histocompatability complex (MHC) and modifications in the cellular responses of this system resulting from three-dimensional culture. The generality of these properties in different cell types is discussed. In contrast, whole organs, that include antigen presenting cells such as endothelial cells that are essential for the viability of tissue-engineered organs, display a marked immune response. These cells, therefore, must be autologous. The differences in manufacturing tissues and organs using allogeneic cells from methods using autologous cells, which is always a service industry, are large in terms of capital requirements, economies of scale and regulatory compliance. The major problem remaining in the transplantation of artificial organs is provision of an adequate vascular supply, which has to be autologus. Several approaches to this problem have been investigated. A successful approach to constructing small-diameter blood vessels, using allogeneic fibroblasts and autologous endothelial cells is presented. The solution to transplantable tissue engineered organs is likely to be a combination of major components of the construct manufactured from minimally immunogenic, allogeneic cells, with an individualized vascular system lined with autologous endothelial cells. However, once transplanted, further questions of the functionality of the organ, prevention of fibrosis and scarring become important and need to be addressed.