|Public on Nov 03, 2017
|Massive and reproducible production of liver buds entirely from human pluripotent stem cells
|Expression profiling by array
|Organoid technology provides a revolutionary paradigm towards therapy, yet to be applied in humans mainly because of the reproducibility and scalability challenges. Here, we overcome these limitations by evolving scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive ‘reverse’ screen experiments, we identified effective triple progenitor populations for generating liver buds in a highly reproducible manner: hepatic endoderm, endothelial and septum mesenchyme progenitors. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass-producing homogenous and miniaturized liver buds on a clinically relevant large scale (>108-cell scale). Vascularized and functional liver tissues generated entirely from iPSC significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacture platform for multi-cellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.
|Transcriptome profiling of iPSC derived liver buds (iPSC-LB), progenitor populations for generating liver buds (iPSC-tHE/iPSC-EC/iPSC-MC) and human liver tissue of various developmental stages.
|Takebe T, Ueno Y, Koido M, Taniguchi H
|Nov 02, 2017
|Last update date
|Jan 24, 2018
|Yokohama City University
|Graduate School of Medicine
|Department of Regenerative Medicine
|3-9 Fuku-ura, Kanazawa-ku
|Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version)
|Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version)