Morpho-elasticity of human pluripotent stem cell cysts

Human induced pluripotent stem cells (hiPSCs) are a promising cellular source in cell therapies or regenerative medicine and they allow to address fundamental mechanisms in embryo-genesis. However, their culture to provide large amounts of high quality stem cells remains challenging. Here, using an encapsulation microfluidic device, we observe that hiPSCs self-organize into cysts, which are spherical closed epithelia reminiscent of the early stages of in vitro embryo models. We monitor their morphology, organization and growth in a pseudo-stratified epithelium before and after they get confined by the capsule wall. Then, we present a morpho-elastic model to quantitatively explain the growth dynamics. The model based on Neo-Hookean elasticity with anisotropic growth shows that the stresses, concentrated within the cyst, remain at a low level. Cyst growth is shown to be quasi-exponential, slightly reduced by a compression-induced correction. We hypothesize that this peculiar morphological dynamics, which is controlled by elasticity and anisotropic growth, might provide new strategies to optimize the production of medical grade hiPSCs.