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3D Intercellular Assembly of Decellularized Matrix Recapitulates In Vivo Tumor Heterogeneity

ABSTRACT: 3D Intercellular Assembly of Decellularized Matrix Recapitulates In Vivo Tumor Heterogeneity

PROVIDER: PRJNA1109522 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28974600_1.fastq.gz	Fastqsanger.gz
	SRR28974600_2.fastq.gz	Fastqsanger.gz
	SRR28974601_1.fastq.gz	Fastqsanger.gz
	SRR28974601_2.fastq.gz	Fastqsanger.gz
	SRR28974602_1.fastq.gz	Fastqsanger.gz

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3D Intercellular Assembly of Decellularized Matrix Recapitulates In Vivo Tumor Heterogeneity

Project description:The tumor microenvironment consists of resident tumor cells organized within a compositionally diverse, three-dimensional (3D) extracellular matrix (ECM) network that cannot be replicated in vitro using bottom-up synthesis. We report a new self-assembly system to engineer ECM-rich 3D MatriSpheres wherein tumor cells actively organize and concentrate microgram quantities of decellularized ECM dispersions which modulate cell phenotype. 3D colorectal cancer (CRC) MatriSpheres were created using decellularized small intestine submucosa (SIS) as an orthotopic ECM source that had greater proteomic homology to CRC tumor ECM than traditional ECM formulations such as Matrigel. SIS ECM was rapidly concentrated from its environment and assembled into ECM-rich 3D stroma-like regions by mouse and human CRC cell lines within 4-5 days via a mechanism that was rheologically distinct from bulk hydrogel formation. Both ECM organization and transcriptional regulation by 3D ECM cues affected programs of malignancy, lipid metabolism, and immunoregulation that corresponded with an in vivo MC38 tumor cell subpopulation identified via single cell RNA sequencing. This 3D modeling approach stimulates tumor specific tissue morphogenesis that incorporates the complexities of both cancer cell and ECM compartments in a scalable, spontaneous assembly process that may further facilitate precision medicine.

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3D Intercellular Assembly of Decellularized Matrix Recapitulates In Vivo Tumor Heterogeneity

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A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity

Project description:The tumor microenvironment consists of resident tumor cells organized within a compositionally diverse, three-dimensional (3D) extracellular matrix (ECM) network that cannot be replicated in vitro using bottom-up synthesis. We report a system to engineer ECM-rich 3D MatriSpheres wherein tumor cells actively organize and assemble microgram quantities of decellularized ECM which in turn modulate cancer phenotype. 3D colorectal cancer (CRC) MatriSpheres were created using decellularized small intestine submucosa (SIS) as an orthotopic ECM source that had greater proteomic homology to CRC tumor ECM than traditional ECM formulations such as Matrigel. SIS ECM was rapidly concentrated from its environment and assembled into ECM-rich 3D stroma-like regions by colorectal cancer cell lines within 4-5 days via a mechanism that was rheologically distinct from bulk hydrogel formation. Both ECM organization and transcriptional regulation by 3D ECM cues were cell line specific, affecting programs of malignancy, lipid metabolism, and immunoregulation that corresponded to an in vivo tumor cell subpopulation identified via single cell RNA sequencing. This 3D modeling approach stimulates tumor specific tissue morphogenesis that incorporates the complexities of both cancer cell and ECM compartments in a scalable, spontaneous assembly process that may further facilitate precision medicine.

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A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity

Project description:A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity

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Delineation of in vitro chondrogenesis of human synovial stem cells following preconditioning with decellularized matrix

Project description:As a tissue-specific stem cell for chondrogenesis, synovium-derived stem cells (SDSCs) are a promising cell source for cartilage repair. However, a small biopsy can only provide a limited number of cells. Cell senescence from both in vitro expansion and donor age presents a big challenge for stem cell based cartilage regeneration. Here we found that expansion on decellularized extracellular matrix (dECM) full of three-dimensional nanostructured fibers provided SDSCs with unique surface profiles, low elasticity but large volume as well as fibroblast-like shape. dECM expanded SDSCs yielded large pellets with intensive staining of type II collagen and sulfated GAGs, which was supported by both biochemical data and real-time PCR results. Our results also hint at lower levels of inflammatory genes and how they might be responsible for enhanced chondrogenic differentiation in dECM expanded SDSCs. Despite an increase of type X collagen in chondrogenically induced cells, dECM expanded cells had significantly lower potential for endochondral bone formation. Both Wnt and MAPK signals were actively involved in both expansion and chondrogenic induction of dECM expanded cells. dECM expanded human SDSCs could be a potential cell source for autologous cartilage repair Adult human synovial fibroblasts (4 donors, two male and two female, average 43 years old, all had no known joint disease) were grown for one passage on plastic flasks (P cells) or plastic flasks pre-coated with decellularized extracellular matrix (E cells). Aliquots were centrifuged and pellets cultured for 35 days in serum-free chondrogenic medium (P pellet or E pellet). There are no replicates.

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Project description:Organoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, the clinical application is greatly limited by the lack of effective GMP-compliant systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix hydrogels derived from decellularized tissues (DT) can provide an environment capable of directing cell growth. These gels possess the biochemical signature of tissue-specific ECM, and have the potential for clinical translation. Gels from decellularized porcine small intestinal mucosa/submucosa enable formation and growth of endoderm-derived human organoids, such as gastric, liver, pancreas, and small intestine. ECM gels could be used for direct organoids derivation from human biopsies, multiple passages with transcriptomic signature comparable to gold standard culture system, and in vivo organoid delivery. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically.

2019-11-05 | GSE138611 | GEO

Extracellular matrix hydrogel derived from decellularized tissues enables endoderm organoids culture

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