Article

Vascularized and functional liver devided from human induced pluripotent stem cells by recapitulating organogenesis

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Abstract

Due to a severe donor shortage crisis, over 100,000 patients waiting for transplants per year die of end-stage organ failure in the United States alone. Laboratory-grown functional organs derived from pluripotent stem cells, such as induced pluripotent stem cells (iPSCs), may be one promising solution to this organ shortage. However, it has been considered impractical to recapitulate in stem cell cultures the spatiotemporal control of the multicellular interactions that occur during embryogenesis to generate a complex and vascularized organ, such as the liver. Recently, we reported that a three-dimensional iPSC-derived rudimentary organ (liver bud) could be grown from mixed human liver progenitors in a specific three-dimensional culture by mimicking early organogenic cellular interactions. The transplantation of this iPSC-derived liver bud was effective in rescuing lethal liver failure, a proof of principle that highlights the enormous therapeutic potential of this approach (i.e., in vitro-grown organ-bud transplantation). The present manuscript provides an overview of this new regenerative paradigm for future clinical application.

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