Biomaterials approach to expand and direct differentiation of stem cells

Abstract

Stem cells play increasingly prominent roles in tissue engineering and regenerative medicine. Pluripotent embryonic stem (ES) cells theoretically allow every cell type in the body to be regenerated. Adult stem cells have also been identified and isolated from every major tissue and organ, some possessing apparent pluripotency comparable to that of ES cells. However, a major limitation in the translation of stem cell technologies to clinical applications is the supply of cells. Advances in biomaterials engineering and scaffold fabrication enable the development of ex vivo cell expansion systems to address this limitation. Progress in biomaterial design has also allowed directed differentiation of stem cells into specific lineages. In addition to delivering biochemical cues, various technologies have been developed to introduce micro- and nano-scale features onto culture surfaces to enable the study of stem cell responses to topographical cues. Knowledge gained from these studies portends the alteration of stem cell fate in the absence of biological factors, which would be valuable in the engineering of complex organs comprising multiple cell types. Biomaterials may also play an immunoprotective role by minimizing host immunoreactivity toward transplanted cells or engineered grafts.

Figure 1. Multiple roles for biomaterials in stem cell TE

Biomaterials play different roles at various stages in the application of stem cells to TE. ESCs may be derived from blastocysts obtained by either fertilization or somatic cell nuclear transfer under xeno-free conditions on biomaterial substrates. Derived stem cells can be expanded in culture on biomaterial-based bioreactors. Tissue scaffolds can be tailored according to the specific goals of the intended therapy. (a) Expanded ESCs can be differentiated terminally into mature cell types before seeding into scaffolds to construct tissues or whole organs. Alternatively, expanded stem cells may be partially differentiated into committed tissue progenitors (proto-tissues) that undergo terminal differentiation in seeded scaffolds (b) before or (c) after implantation into the body. In the latter case, the progenitor cells may continue to proliferate and migrate outward from the implanted graft to repair lesioned areas. (d) Injectable grafts for both soft and hard tissue regeneration may be produced by encapsulating progenitor or fully differentiated cells in biodegradable hydrogels. Somatic stem cells isolated from pediatric or adult patients can similarly be expanded in a biomaterials-based culture system before being applied as described for ES-derived cells.