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Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE66454 | GEO | 2015/07/01

SECONDARY ACCESSION(S): PRJNA277141

REPOSITORIES: GEO

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Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation

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

Mus musculus

Project description:Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation

| PRJNA277141 | ENA

Effects of dynamic compressive loading on MSC chondrogenesis

Project description:Long-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling). Free-swelling MSC-seeded constructs were cultured for 21 days in chemically defined media. Chondrogenesis was induced with TGF-beta3. Undifferentiated controls were maintained in parallel. After 21 days of chondrogenic differentiation, a subset of constructs were subjected to 21 days of dynamic compressive loading. On days 21 and 42, construct mechanical properties and biochemical content were assessed. Microarray analysis was carried out on day 3, day 21 and day 42 constructs. 6 arrays.

2010-11-01 | E-GEOD-18879 | biostudies-arrayexpress

Magnesium promotes vascularized osseointegration in diabetic states

Project description:The poor osseointegration of dental implants in diabetic patients has become a long-standing clinical problem. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes vascularized osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants sucessfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data proved that Mg2+ promoted vascularized osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

2024-02-07 | GSE236139 | GEO

Effects of dynamic compressive loading on MSC chondrogenesis

2010-11-01 | GSE18879 | GEO

Bi-directional Impacts of Heterotypic Interactions in Engineered 3D Human Cardiac Microtissues Revealed by Single-Cell RNA-Sequencing and Functional Analysis

Project description:Technological advancements have enabled the design of increasingly complex engineered tissue constructs, which better mimic native tissue cellularity. Therefore, dissecting the bi-directional interactions between distinct cell types in 3D is necessary to understand how heterotypic interactions at the single-cell level impact tissue-level properties. We systematically interrogated the interactions between cardiomyocytes (CMs) and cardiac non-myocytes in 3D self-assembled tissue constructs in an effort to determine the phenotypic and functional contributions of cardiac fibroblasts (CFs) and endothelial cells (ECs) to cardiac tissue properties. One week after tissue formation, cardiac microtissues containing CFs exhibited improved calcium handling function compared to microtissues comprised of CMs alone or CMs mixed with ECs, and CMs cultured with CFs exhibited distinct transcriptional profiles, with increased expression of cytoskeletal and ECM-associated genes. However, one month after tissue formation, functional and phenotypic differences between heterotypic tissues were mitigated, indicating diminishing impacts of non-myocytes on CM phenotype and function over time. The combination of single-cell RNA-sequencing and calcium imaging enabled the determination of reciprocal transcriptomic changes accompanying tissue-level functional properties in engineered heterotypic cardiac microtissues.

2020-09-21 | GSE155226 | GEO

3D vascularized proximal tubule model improves cell phenotype

Project description:3D vascularized proximal tubule model improves cell phenotype

| PRJNA817064 | ENA

Single-cell RNA sequencing of vascularized brain organoids

Project description:Single-cell RNA sequencing of vascularized brain organoids

| PRJNA427709 | ENA

Vascularized human cortical organoids (vOrganoid) model cortical development in vivo

Project description:Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoids (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of sEPSCs (spontaneous excitatory postsynaptic currents), sIPSCs (spontaneous inhibitory postsynaptic currents) and bidirectional electrical transmission indicated the presence of chemical and electrical synapses in vOrganoids. More importantly, single-cell RNA-sequencing analysis illustrated that vOrganoids exhibited robust neurogenesis and that cells of vOrganoids differentially expressed genes related to blood vessel morphogenesis. The transplantation of vOrganoids into the mouse S1 cortex resulted in the construction of functional human-mouse blood vessels in the grafts that promoted cell survival in the grafts. This vOrganoid culture method could not only serve as a model to study human cortical development and explore brain disease pathology but also provide potential prospects for new cell therapies for nervous system disorders and injury.

2020-06-04 | GSE131094 | GEO

tsRNAs Are Potential Biomarkers of Acute Rejection in Vascularized Composite Allotransplantation

Project description:Purpose: to explore the function and mechanism of acute rejection in vascularized composite allotransplantation Method: tRF & tiRNA profiles of acute rejection in vascularized composite allotransplantation were generated by deep sequencing, using Illumina NextSeq 500. qRT–PCR validation was performed using SYBR Green assays. Results:Sequencing was used to screen expression profiles and predict target genes. Compared with the control group, there were significant differences in the expression levels of 16 tRFs & tiRNAs, including 5 up-regulated target genes and 11 down-regulated target genes. Bioinformatics analysis and RT-qPCR revealed potential up regulation of tRFs & tiRNAs(tiRNA-1-33-Gly-GCC-1, tiRNA-1-34-Glu-CTC-1, tRF-1-32-Gly-GCC-2-M2) and down regulation of tRFs & tiRNAs (tRF-59:75-Gln-CTG-2-M2, tRF-59:76-Val-AAC-1-M2). Conclusion: In conclusion, it is speculated that tiRNA-1-34-Glu-CTC-1 plays an important role in VCA induced acute rejection by regulating CACNA1D gene in MAPK signaling pathway. This provides a new insight into the mechanism and therapeutic targets of acute rejection.

2022-07-20 | GSE190008 | GEO

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