Scalable generation of human stem cell-derived ureteric bud and collecting duct organoids in stirred bioreactors
Kayla J. WolfiD, Jonathan E. RubinsiD, Ronald C. van GaaliD, Kyles Stevens, Aline N. KlausiD, Pooja NairiD, Jennifer A. LewisiD
Abstract
Emerging efforts to engineer multicellular kidney tissues for drug discovery, disease modeling, and therapeutic repair require scalable generation of kidney organoids derived from human induced pluripotent stem cells (hiPSCs). Here, we report a method for generating kidney ureteric bud and collecting duct epithelial organoids in stirred tank bioreactors. We demonstrate that extracellular matrix microcarriers facilitate organoid expansion and are compatible with suspension bioreactor methods. The combination of cell-coated matrix microcarriers with stirred bioreactors promotes maturation marker expression compared to static controls comprising matrix-embedded organoids. Our method offers promise for generating epithelial organoids that serve as multicellular models and organ building blocks for scalable biofabrication.
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