3D Bioprinting Lobule-like Hepatorganoids with Induced Vascularization for Orthotopic Implantation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1123658 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Orthotopic implantation tumor assays are frequently employed in tumor biology, drug screening, and personalized therapy researches. However, the limited representation of a complex tumor microenvironment in these implanted animal models hampers a comprehensive understanding of tumor progression and therapeutic response. In this research, we developed a 3D bioprinting method using gelatin methacryloyl (GelMA) hydrogel loaded with a prolonged released system of vascular endothelial growth factor (VEGF), embedding hepatocellular carcinoma cells, to fabricate lobule-like hepatorganoids that faithfully mimic the architecture of hepatic lobules. Moreover, we utilized GelMA hydrogel mixed with Matrigel, containing human umbilical vein endothelial cells (HUVECs), to induce vascularization on the organoids. Orthotopic implantation in mouse model was performed, allowing for an improved simulation of the vascularization process within hepatorganoids. Compared to control group, 3D bioprinted lobule-like hepatorganoids exhibited prolonged survival in mice, while serum analysis revealed significantly elevated levels of alpha-fetoprotein (AFP). Eventually, our findings demonstrate that this system effectively forms orthotopic implantion of liver tumors and facilitates vascularization, which may notably contribute to the understanding of tumor biology, drug screening, and personalized therapy.
2025-02-12 | GSE269768 | GEO
Project description:Metastasis is a major factor for mortality in patients with hepatocellular carcinoma (HCC). Thus, there is a need for predictive biomarker(s) for detecting the tipping point before metastasis, so as to prevent further deterioration. To discover early warning signals of pulmonary metastasis in HCC, we analysed time-series gene expression data in the spontaneous pulmonary metastasis mouse HCCLM3-RFP model with our novel dynamic network biomarker (DNB) method. To simulate tumour growth and metastasis in patient livers, we used the spontaneous pulmonary metastasis mouse model, HCCLM3-RFP, which involves the orthotopic transplanted human HCCLM3 cell line labelled with a stable fluorescent protein.We observed that, hepatic tumours in orthotopic xenograft HCCLM3-RFP mice grew gradually from the second to the fifth week after orthotopic implantation in the primary liver tissue, whereas spontaneous pulmonary metastasis occurredonly at the last time point (the fifth week after orthotopic implantation).Thus, we chose the second, third, fourth, and fifth weeks after orthotopic implantation as observation points to collect liver tumours of five orthotopic xenograft mice at each time point and to assess the whole-genome expression.
2017-06-01 | GSE94016 | GEO
Project description:Pterygium is an ocular surface disorder with high prevalence that can lead to vision impairment. As a pathological outgrowth of conjunctiva, pterygium involves neovascularization and chronic inflammation, but its pathogenesis remains largely unknown. Over the last decade, various types of disease models have been built to study pterygium. Here, we developed a 3D multicellular in vitro pterygium model using the digital light processing (DLP)-based 3D bioprinting of human conjunctival stem cells (hCjSCs). A novel feeder-free culture system was adopted and efficiently expanded the primary hCjSCs with homogeneity, stemness and differentiation potency. The DLP-based 3D bioprinting was able to fabricate hydrogel scaffolds that support the viability and biological integrity of the encapsulated hCjSCs. The bioprinted 3D pterygium model was fabricated with hCjSCs, immune cells and vascular cells to recapitulate the disease microenvironment. Transcriptomic analysis using RNA sequencing (RNA-seq) identified a distinct profile correlated to inflammation response, angiogenesis, and epithelial mesenchymal transition in the bioprinted 3D pterygium model. In addition, the pterygium signatures and disease relevance of the bioprinted model were validated with the public RNA-seq data from patient-derived pterygium tissues. By integrating the stem cell technology and 3D bioprinting, this is the first reported 3D in vitro disease model for pterygium that can be utilized by future studies towards the personalized medicine and the drug screening.
2022-06-01 | GSE180343 | GEO
Project description:Capturing cell-to-cell and cell-to-environment signals in a defined 3 dimensional (3D) microenvironment is key to study cellular functions, including cellular reprogramming towards tissue regeneration. A major challenge in current culturing methods is that these methods cannot accurately capture this multicellular 3D microenvironment. In this study, we established the framework of 3D bioprinting with plant cells to study cell viability, cell division, and cell identity. To investigate the cellular reprogramming underlying the initial cell divisions prior to microcallus formation, we collected RNA from isolated differentiated root cells immediately, 1, and 3 days after bioprinting. We showed the cell cycle re-entry of the isolated Arabidopsis and soybean cells leading to the formation of microcalli and of which the timing coincides with the induction of core cell cycle genes and regeneration-related genes. Finally, we showed that the identity of isolated cells of Arabidopsis roots expressing endodermal markers maintained longer periods of time. The framework established in this study paves the way for a general use of 3D bioprinting for studying cellular reprogramming and cell cycle re-entry towards tissue regeneration.
2022-08-15 | GSE208176 | GEO
Project description:Background & Aims: 3D Bioprinting of an endocrine pancreas is a promising future curative treatment for selected patients with insulin secretion deficiency. In this study we present an end-to-end integrative, scalable concept extending from the molecular to the macroscopic level. Methods: A hybrid scaffold device was manufactured by 3D (bio)printing. INS-1 cells with/without endothelial cells were bioprinted in gelatin methacrylate blend hydrogel. Polycaprolactone was 3D-printed and heparin-functionalized as structural scaffold component. In vitro evaluation was performed by viability and growth assays, total mRNA sequencing, and glucose-stimulated insulin secretion. In vivo, xenotransplantation to fertilized chicken eggs was used to investigate vascularization and function, and finite element analysis modeling served to detect boundary conditions and applicability for human islets of Langerhans. Results: Insulin-secreting pseudoislets were formed and resulted in a viable and proliferative experimental model. Transcriptomics revealed upregulation of proliferative and ß-cell-specific signaling cascades, downregulation of apoptotic pathways, and overexpression of extracellular matrix proteins and VEGF induced by pseudoislet formation and 3D culture. Co-culture with human endothelial cells created a natural cellular niche resulting in enhanced insulin response after glucose stimulation. Survival and function of the pseudoislets after explantation and extensive scaffold vascularization of both the hydrogel and heparinized polycaprolactone components were demonstrated in ovo. Computer simulations of oxygen, glucose, and insulin flows were used to evaluate scaffold architectures and Langerhans islets at a future transplantation site along neurovascular structures. Conclusion: A defined end-to-end process for multidisciplinary bioconvergence research on a bioartificial endocrine pancreas was developed. A modular, patient-specific device architecture is proposed for future research studies.
2021-02-19 | GSE166285 | GEO
Project description:Improved patient-derived tumor models in pancreatic ductal adenocarcinoma employing orthotopic implantation
| PRJNA661474 | ENA
Project description:Studying primary Chronic Lymphocytic Leukemia cells in vitro is very challenging due to their short survival in culture, and also due to the fact that traditional two-dimensional in vitro models lack cellular and spatial complexity present in vivo. Based on these considerations, we exploited three-dimensional (3D) bioprinting to advance in vitro models for CLL. Through RNA sequencing (RNAseq) analysis, we observed a consistent difference in gene expression profile between 2D and 3D samples, indicating a different behavior of the cells in the two different culture settings.
2021-04-21 | GSE163977 | GEO
Project description:Rapid 3D Bioprinting of Multicellular Model Recapitulating Pterygium Microenvironment
| PRJNA748455 | ENA
Project description:Bioprinting is an emerging additive manufacturing approach to the fabrication of patient-specific, implantable three-dimensional (3D) constructs for regenerative medicine. However, developing cell-compatible bioinks with high printability, structural stability, biodegradability, and bioactive characteristics is still a primary challenge for translating 3D bioprinting technology to preclinical and clinal models. To overcome this challenge, we develop a nanoengineered ionic covalent entanglement (NICE) bioink formulation for 3D bone bioprinting. The NICE bioinks allow precise control over printability, mechanical properties, and degradation characteristics, enabling custom 3D fabrication of mechanically resilient, cellularized structures. We demonstrate cell- induced remodeling of 3D bioprinted scaffolds over 60 days, demonstrating deposition of nascent extracellular matrix proteins. Interestingly, the bioprinted constructs induce endochondral differentiation of encapsulated human mesenchymal stem cells (hMSCs) in absence of osteoinducing agents such as dexamethasone or bone morphogenic protein-2 (BMP-2). Using next-generation transcriptome sequencing (RNA-seq) technology, we establish the role of nanosilicates, a bioactive component of NICE bioink, to stimulate endochondral differentiation at the transcriptome level. Overall, the osteoinductive bioink has the ability to induce formation of osteo-related mineralized extracellular matrix by encapsulatedhMSCsingrowthfactor-freeconditions.Furthermore,wedemonstratedtheabilityofNICEbioinktofabricatepatient-specific, implantable 3D scaffolds for repair of craniomaxillofacial bone defects. We envision transformation of this NICE bioink technology toward a realistic clinical process for 3D bioprinting patient-specific bone tissue for regenerative medicine.
2020-03-04 | GSE146309 | GEO
Project description:Pancreatic ductal adenocarcinoma has a very poor prognosis, and new therapies and preclinical models are urgently needed. We developed patient-derived xenografts (PDXs), established PDX-derived cell lines (PDCLs), and generated cell line-derived xenografts (CDXs), and integrated these to create 13 matched trios, as systematic models for this cancer. Orthotopic implantation (OI) of PDCLs showed tumorigenesis and metastases to the liver and peritoneum. Morphological comparisons of OI-CDX and OI-PDX with passaged tumors showed that histopathological features of the original tumor were maintained in both models. Molecular alterations in PDX tumors (including those to KRAS, TP53, SMAD4, and CDKN2A) were similar to those in the respective PDCLs and CDX tumors. Comparing gene expression in PDCLs, ectopic tumors, and OI tumors, CXCR4 and CXCL12 genes were specifically upregulated in OI tumors, whose immunohistochemical profiles suggested epithelial-mesenchymal transition and adeno-squamous trans-differentiation. These patient-derived tumor models provide useful tools for preclinical research into pancreatic ductal adenocarcinoma. We performed comprehensive gene expression profiling of 13 pancreatic cancer cell lines, 14 CDX and 14 PDX tumors by Affymetrix Gene Chip HG-U133Plus2.0.
2022-02-16 | GSE157494 | GEO