Transplantation of engineered cells and tissues

Abstract

Publisher Summary Despite experience with organ transplantation, implantation of tissue-engineered products containing live cells has thus far shown no clinical evidence for immune rejection. Limited testing for specific mechanisms of rejection has shown no evidence of humoral or cell-mediated reaction to the implants. The major reason for the lack of immunogenicity lies in the lack of antigen-presenting cells in the implants and inclusion of such cells has been found experimentally to confer reject ability. In a transplanted organ, endothelial cells are a major source of antigen-presenting cells and acute rejection may be seen as an attack on the vascular system that rapidly extends to other cells. It has also been found that fibroblasts in scaffold-based 3D culture show a selective response to γ-interferon, which, although it induces molecules associated with antigen presentation in many cell types under suitable culture conditions, does not do so in this case. The use of allogeneic cells has many advantages for manufacturing, even if it can be applied only to part of the final construct; therefore, it would be valuable to ascertain the scope of cells types immune to rejection. At present, it applies to fibroblasts and smooth muscle cells, but not to endothelial cells or hemopoietic cells, although claims have been made for bone marrow stem cells including their ability to suppress responses to allogeneic cells. In the case of stem cells, it may be true that undifferentiated cells are non-immunogenic but that they may become immunogenic if they differentiate into antigen-presenting cells, such as macrophages, dendritic cells, and endothelial cells. Determination of the range of cells showing minimal immunogenicity would be a valuable contribution to tissue engineering.