Human embryonic stem cells (hESCs) require a supportive niche consisting of appropriate cues and signals. These niches can maintain hESCs in an undifferentiated state or promote their differentiation into specific phenotypes, depending on their properties. Biomaterial scaffolds can be engineered to provide such regulatory cues and thereby support and control these important cell functions. This updated chapter details the major types of scaffold materials currently employed for such applications and evaluates their use for maintaining hESC pluripotency or directing differentiation into desired lineages. Scaffold materials are classified as natural or synthetic, and the advantages and drawbacks of each material are discussed along with relevant examples taken from the literature. Finally, the current status of research in engineering biomaterial scaffolds for the culture and differentiation of hESCs along with future directions are given.

HESC are derived from the inner cell mass of an embryonic blastocyst five days after fertilization. hESC are undifferentiated pluripotent stem cells that have the capacity to either self-renew indefinitely or to differentiate into any cell in the body when exposed to the correct combination of signaling and growth factors. hESC lines are clonal populations of undifferentiated hESC maintained indefinitely in vitro. Knowledge of the regulatory mechanisms that induce lineage commitment in embryos has been used to systematically obtain highly enriched populations of differentiated cells from hESC lines. Differentiation of these cells is a multi-step process. Initially, regulatory signaling pathways are manipulated to induce the formation of mesoderm, endoderm, or ectoderm germ layers in vitro. Germ layer specific tissues can be produced from each. Hematopoietic, vascular, and cardiac cells can be obtained from mesoderm; hepatocytes and pancreatic cells from endoderm; and neural cells from ectoderm. When injected into immune deficient mice, hESC form teratomas containing cells derived from all germ layers. This has raised safety concerns regarding the tumorigenicity of hESC derived therapies. To improve safety, development of therapies from hESC has focused primarily on the development of specific differentiated cell populations from these cells. Purity and potency assays for these products must include safeguards to ensure that the final cellular therapy product does not contain undifferentiated tumorigenic stem cells.

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