The original model for tissue engineering focused largely on the isolation of tissue from the organ of interest, the growth and expansion of the tissue-specific cells, and the seeding of these cells onto three-dimensional scaffolds. Just a few decades ago, most primary cultures of human cells could not be grown and expanded in large quantities, representing a major impediment to the engineering of human tissues. However, the identification of specific tissue progenitor cells in the 1990s allowed expansion of multiple cell types, and progress has occurred steadily since then. Some cell types are more amenable to expansion than others, reflecting in part their native regenerative capacity but also varying requirements for nutrients, growth factors, and cell–cell contacts. As an example of progress, after years of effort, protocols for the growth and expansion of human cardiomyocytes are now available. However, there are still many tissue-specific cell types that cannot be expanded from tissue sources, including the pancreas, liver, and nerves. The discovery of pluripotent or highly multipotent stem cells (Chap. 88) may ultimately allow most human cell types to be used for tissue engineering. The stem cell characteristics depend on their origin and their degree of plasticity, with cells from the earliest developmental stages, such as embryonic stem cells, having the greatest plasticity. Induced pluripotent stem cells have the advantage that they can be derived from individual patients, allowing autologous transplants. They can also be differentiated, in vitro, along cell-specific lineages, although these protocols are still at an early stage of development. Human embryonic and induced pluripotent stem cells have a very high replicative potential, but they also have the potential for rejection and tumor formation (e.g., teratomas). The more recently described amniotic fluid and placental stem cells have a high replicative potential but without an apparent propensity for tumor formation. Moreover, they have the potential to be used in an autologous manner without rejection. Adult stem cells, such as those derived from bone marrow, also have less propensity for tumor formation and, if used in an autologous manner, will not be rejected, but their replicative potential is limited, especially for endoderm and ectoderm cells.
Stem cells can be derived from autologous or heterologous sources. Heterologous cells can be used when only temporary coverage is needed, such as replacing skin after a burn or wound. However, if a more permanent construct is required, autologous cells are preferred to avoid rejection. There are also practical issues related to tissue sources. For example, if a patient presents with end-stage heart disease, obtaining a cardiac tissue biopsy for cell expansion is unlikely to be feasible, and bone marrow–derived mesenchymal cells may provide an alternative.