Human pluripotent stem cell (hPSC) differentiation aims to mimic development using growth factors or small molecules in a time-dependent and dose-dependent manner. However, the cell types produced using this approach are predominantly fetal-like in phenotype and function, limiting their use in regenerative medicine. This is particularly true in current efforts to produce pancreatic beta cells, wherein robust pancreatic progenitor maturation can only be accomplished upon transplantation into mice. Recent studies have suggested that hPSC-derived cells are capable of self-organizing in vitro, revealing a new paradigm for creating mature cells and tissues. Tissue engineering strategies that provide subtle and dynamic signals to developmentally naïve cells may be applied to mimic in vitro the self-organization aspects of pancreatic development.
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