Vascularised and functional human liver from an iPSC-derived organ bud transplant
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA201333 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from induced pluripotent stem cells (hiPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularised organ such as liver. Here, we show the generation of vascularised and functional human liver from hiPSCs by transplantation of liver buds created in vitro (hiPSC-LBs). Specified hepatic cells self-organised into three-dimensional hiPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene expression analyses revealed resemblance between in vitro grown hiPSC-LBs and in vivo liver buds. Human vasculatures in hiPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of hiPSC-LBs into tissue resembling the adult liver. Highly metabolic hiPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement. Comparison of liver developmental gene signatures among hiPSC-LB, hFLC-LB, human adult (30 years old) liver tissues (hALT) and mouse liver tissue (mLT) of various developmental stages (E9.5~P8weeks).
2013-07-01 | E-GEOD-46631 | biostudies-arrayexpress
Project description:Critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from induced pluripotent stem cells (hiPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularised organ such as liver. Here, we show the generation of vascularised and functional human liver from hiPSCs by transplantation of liver buds created in vitro (hiPSC-LBs). Specified hepatic cells self-organised into three-dimensional hiPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene expression analyses revealed resemblance between in vitro grown hiPSC-LBs and in vivo liver buds. Human vasculatures in hiPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of hiPSC-LBs into tissue resembling the adult liver. Highly metabolic hiPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement.
2013-07-01 | GSE46631 | GEO
Project description:TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients and longitudinal data from renal and liver transplant recipients.
| EGAS00001006258 | EGA
Project description:Gut microbiota associated with organ transplant outcome Targeted loci environmental
| PRJNA480643 | ENA
Project description:The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
| 2262897 | ecrin-mdr-crc
Project description:This study determined key transcriptional signatures associated with HCV recurrence and eventual development of severe liver disease in infected transplant patient liver biopsies over time following transplant. We identified molecular signatures associated with severe fibrosis and liver injury prior to histologic evidence of disease progression. 111 liver biopsy specimens collected longitudinally from 57 HCV-infected liver transplant patients following organ transplant. Several batches of pooled normal liver RNA samples (Utah normal pool; UNP) are included.
2012-02-10 | E-GEOD-34798 | biostudies-arrayexpress
Project description: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.
2018-01-10 | GSE108937 | GEO
Project description:Here we report single-cell RNA-sequencing generated from one COVID-19 lung removed at the time of organ transplant.
2020-12-29 | GSE163919 | GEO
Project description:TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from renal transplant recipients is.
| EGAS00001006257 | EGA
Project description:Conventional 2-D differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. 3-D organoids generate complex organ-like tissues, however it is unclear how heterotypic interactions impact lineage identity. Here we use single-cell RNA-seq to reconstruct hepatocyte-like lineage progression from pluripotency in 2-D culture. We then derive 3-D liver bud (LB) organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during LB self-organization. We find that LB hepatoblasts differentiate towards hepatocyte fate, and in addition express epithelial migration signatures characteristic of organ budding. We identify hypoxia and inflammation signatures in endothelial and mesenchymal cells, which we suggest induce LB vasculogenesis. We use network analysis to predict autocrine and paracrine signaling in LBs, and show that VEGF crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals inter-lineage communication that is required for self-organization, and illuminates previously inaccessible aspects of human organ development and regeneration.
2017-02-08 | GSE81252 | GEO