An Engineered Multicellular S tem Cell Niche forS tudying Disease, Aging and Regeneration

Fate decisions in the embryo are controlled by a plethora ofmicroenvironmental interactions in a three-dimensional niche.Different bioengineering s trategies, such as heterotypic suspensionembryoids, organoids, and encapsulation technologies,have been developed and utilized in our group to determineif aspects of this microenvironmental complexity canbe engineered to mimic s tem cell niches and direct s tem celldifferentiation. For example, we es tablished a method for theencapsulation of human and mouse skeletal muscle progenitorsin diffusible polyethersulfone hollow fiber capsules that can beused to profile sys temic aging independent of heterogeneousshort-range tissue interactions. Due to the intrinsic complexityof tissues, it remains challenging to pinpoint niche-independenteffects of circulating factors on specific cell populations. Thismethod allows us the characterization of effector pathways ofsys temic aging with unparalleled accuracy. As another example,we introduced a novel means for the generation of largequantities of human myogenic progenitors in a biologicallyfaithful ۳D niche environment using an organotypic setting.The scalability of organoid cultures allows for production atthe bioreactor level and, next to much-needed cell therapy applicationsfor genetic skeletal muscle diseases, will allow forextensive in vitro modeling and screening applications.