Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA277141 | ENA |
REPOSITORIES: ENA
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Project description:Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine. Gene expression profiles of development-related gene expression in kidney bud transplants and murine kidneys.
2015-07-01 | E-GEOD-66454 | biostudies-arrayexpress
Project description:Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine.
2015-07-01 | GSE66454 | GEO
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.
2017-11-03 | GSE106465 | GEO
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
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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).
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Project description:Vascular flow delivers nutrients and imposes hemodynamic forces that govern vessel behavior in health and disease, yet fully human systems that recapitulate and tune physiological intraluminal flow in three-dimensional (3D) tissues are lacking. We developed VIVOS (Vascularized In Vitro Organ Systems), a platform that couples perfused human vascular beds to tunable pumps, generating continuous intraluminal flow through millimetre-scale vessels and 3D tissues at physiological shear stresses and pressures. VIVOS supports integration and perfusion of diverse human organoids and tissues, including lung organoids, cerebral organoids, vascular organoids, breast spheroids, and human retinal explants, as well as enables direct measurement and control of pressure, shear stress, and perfusion-dominant compound transport over extended culture periods. By tuning intraluminal flow and applying single-cell transcriptomics, we uncover a remodeling program in which laminar shear stress acts through a YAP/TAZ-TEAD “switch” to rewire an Apelin ligand-receptor axis and bias tip-stalk endothelial states, reshaping human vascular networks and linking hemodynamic cues to cell state transitions. We further model fast-flow arteriovenous malformations (AVMs) from Hereditary Hemorrhagic Telangiectasia and show that BMP9 constrains vessel caliber and perfusion while antagonizing a VEGF-driven angiogenic program, generating flow-quantified AVM-like lesions in a fully human 3D context. Together, these findings establish VIVOS as a generalizable platform that links physiological intraluminal flow to endothelial state transitions and vessel remodeling, enabling preclinical testing and mechanistic dissection of flow-regulated vascular pathologies in perfused 3D human tissues under defined hemodynamic conditions.
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Project description:Vascular flow delivers nutrients and imposes hemodynamic forces that govern vessel behavior in health and disease, yet fully human systems that recapitulate and tune physiological intraluminal flow in three-dimensional (3D) tissues are lacking. We developed VIVOS (Vascularized In Vitro Organ Systems), a platform that couples perfused human vascular beds to tunable pumps, generating continuous intraluminal flow through millimetre-scale vessels and 3D tissues at physiological shear stresses and pressures. VIVOS supports integration and perfusion of diverse human organoids and tissues, including lung organoids, cerebral organoids, vascular organoids, breast spheroids, and human retinal explants, as well as enables direct measurement and control of pressure, shear stress, and perfusion-dominant compound transport over extended culture periods. By tuning intraluminal flow and applying single-cell transcriptomics, we uncover a remodeling program in which laminar shear stress acts through a YAP/TAZ-TEAD “switch” to rewire an Apelin ligand-receptor axis and bias tip-stalk endothelial states, reshaping human vascular networks and linking hemodynamic cues to cell state transitions. We further model fast-flow arteriovenous malformations (AVMs) from Hereditary Hemorrhagic Telangiectasia and show that BMP9 constrains vessel caliber and perfusion while antagonizing a VEGF-driven angiogenic program, generating flow-quantified AVM-like lesions in a fully human 3D context. Together, these findings establish VIVOS as a generalizable platform that links physiological intraluminal flow to endothelial state transitions and vessel remodeling, enabling preclinical testing and mechanistic dissection of flow-regulated vascular pathologies in perfused 3D human tissues under defined hemodynamic conditions.
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