Some critical problems associated with the tissue engineering of vital organs: Strategies for vascularisation and immune acceptance

The LIFE Initiative was created with the goal of using tissue engineering to create an essentially unlimited supply of vital organs (heart, kidney, liver) for transplantation. Among the many critical technologies that need to be developed to enable this, one is the ability to create an internal vasculature and thereby provide oxygen to all cells. One such strategy is to use angiogenic growth factors in our case using microencapsulated genetically modified cells. The microencapsulation membrane prevents cell-cell contact facilitating perhaps the construction of thick slabs of tissues using multiple cell types. Another limitation of this approach is the immune response to antigens shed from the encapsulated cells. In separate experiments, Chinese hamster ovary (CHO) cells were microencapsulated in a permeable shell of poly(HEMA:MMA), then implanted in the peritoneal cavity of Balb/c mice using a minimally invasive procedure. Ten days after implant, minimal splenocyte proliferation in MLRs was elicited by encapsulated or naked cells, though significant proliferation was observed if implant duration was extended to two months. Antibody response was present at ten days and two months, though it was significantly greater if the cells were not protected by microcapsules. These results and others highlight the complexity of the immune response and the difficulty of preventing immune recognition of tissue constructs.