Impact of 3D-printed perfusable synthetic vasculature on stem-cell based early-stage cerebral organoids
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE287254 | GEO | 2026/01/01
REPOSITORIES: GEO
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Project description:Impact of 3D-printed perfusable synthetic vasculature on stem-cell based early-stage cerebral organoids
| PRJNA1211734 | ENA
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Project description:Blood vessels play a critical role in pancreatic islet function, yet current methods for deriving islet organoids from human pluripotent stem cells (SC-islets) lack vasculature. We engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca2+ influx into SC-β-cells, a hallmark of β-cell function that is blunted in non-vascularized SC-islets. Furthermore, vascularization accelerated diabetes reversal post-engraftment of a subtherapeutic SC-islet dose. We show that vasculature leads to formation of an islet-like basement membrane that contributes to functional improvement of SC-β-cells. Furthermore, scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-β cells, and correspondingly, BMP4 enhanced the SC-β cell Ca2+ response and insulin secretion. Vascularized SC-islets will enable further studies of crosstalk between β-cells and ECs and will serve as an in vitro platform for disease modeling and therapeutic testing.
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Project description:Vascularization and efficient perfusion are long-standing challenges in cardiac tissue engineering. Here, we engineer perfusable microvascular constructs, wherein human embryonic stem cell-derived endothelial cells (hESC-ECs) are seeded both into patterned microchannels and the surrounding collagen matrix. In vitro, the hESC-ECs lining the luminal walls readily sprout and anastomose with de novo-formed endothelial tubes in the matrix under flow. When implanted on infarcted rat hearts, the perfusable microvessel grafts integrate with coronary vasculature to a greater degree than non-perfusable self-assembled constructs at 5 days post-implantation. Optical microangiography imaging reveal that perfusable grafts have 6-fold greater vascular density, 2.5-fold higher vascular velocities and >20-fold higher volumetric perfusion rates. Implantation of perfusable grafts containing additional hESC-derived cardiomyocytes show higher cardiomyocyte and vascular density. Thus, pre-patterned vascular networks enhance vascular remodeling and accelerate coronary perfusion, potentially supporting cardiac tissues after implantation. These findings should facilitate the next generation of cardiac tissue engineering design.
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Project description:Blood vessels play a critical role in pancreatic islet health and function, yet current culture methods to generate islet organoids from human pluripotent stem cells (SC-islets) lack a vascular component. Here, we engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts both in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca2+ influx into SC-β-cells; a hallmark of β-cell function that is blunted in non-vascularized SC-islets. We show that an islet-like basement membrane is formed by vasculature and contributes to the functional improvement of SC-β-cells. Furthermore, cell-cell communication networks based on scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-β-cells. Correspondingly, BMP4 augmented the SC-β-cell Ca2+ response and insulin secretion. The here-described vascularized SC-islet models will enable further studies of crosstalk between β-cells and ECs and serve as an in vivo-mimicking platform for disease modeling and therapeutic testing.
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Project description:The effect of radiation therapy on tumor vasculature has long been a subject of debate. Increased oxygenation and perfusion have been documented during radiation treatments. Conversely, apoptosis of irradiated tumor endothelial cells has been proposed as a major determinant of tumor control. To approach these contradictions, we used multiphoton microscopy in two murine tumor models: MC38, a highly vascularized and B16F10, a moderately vascularized model, grown in transgenic mice with tdTomato labelled endothelium. These tumors received either a single dose of radiation (15 Gy) or a fractionated dose (5x3 Gy). Unexpectedly, even these high doses led to little structural change of the perfused vasculature. However, non-perfused vessels and blind ends were substantially impaired after radiation accompanied by apoptosis of their endothelium. Additionally, proliferation of endothelium was blocked. Further, RNAseq confirmed the modification of gene expression in apoptotic and cell cycle regulation pathways. Therefore, we show that apoptosis of tumor endothelial cells after radiation does not impair vascular structure.
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Project description:3D-printed porous scaffolds have emerged as a potential solution for treating critical-sized bone defects, yet localized inflammatory imbalance leads to suboptimal therapeutic outcomes. This study utilized nHA/PA66 composite material as the foundation, employing APF additive manufacturing technology to fabricate a three-dimensional porous scaffold (HP) suitable for local bone filling, and functionalized the porous scaffold through modification with polydopamine and magnesium ions (Mg2+) (HPDM). First, the physicochemical properties and biosafety of the HPDM scaffold were verified, followed by a comparative analysis of its effects on macrophage phenotype transformation, vascular endothelial cell differentiation, and pre-osteoblast differentiation differences. The HPDM scaffold achieves coordinated balance in the transformation between M1 and M2 macrophages through sustained release of polydopamine and Mg2+. Mg2+ plays a crucial role in inflammatory regulation by downregulating the NF-κB signaling pathway. Furthermore, several experiments demonstrated that the HPDM scaffold regulates orderly inflammatory responses to promote intercellular interactions, stimulating angiogenesis and osteogenic regeneration. In New Zealand rabbits' femoral condyle bone defect model, the HPDM porous scaffold achieved significant vascularized bone regeneration. This study confirms that the functionalized HPDM porous scaffold prepared using nHA/PA66 as the base material has significant potential in regulating immune responses and enhancing vascularized bone regeneration.
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Project description:Primitive macrophages enhance a perivascular niche to enable vascular perfusion in human cardiac tissue The intricate anatomical structure and high cellular density of the myocardium significantly complicate the bioengineering of vascular networks within cardiac tissues, creating challenges in establishing a perfusable and stable vasculature within these tissues. Emerging evidence from murine in vivo studies underscores the significant role of resident cardiac macrophages in facilitating cardiac regeneration post-injury, specifically their role in enhancing angiogenesis. Here, for the first time, we integrate human pluripotent stem cell derived macrophages, resembling primitive yolk-sac derived macrophages, within human in vitro vascularized heart-on-chip platforms. The incorporation of primitive macrophages had a profound impact on the long term functionality of microvascularized cardiac tissue, particularly in enabling formation of perfusable vasculature with a stable barrier function that persisted for two weeks in culture. These effects were contingent on physical cell-cell interactions and significantly diminished in transwell culture. The inclusion of primitive macrophages mitigated tissue cytotoxicity and curtailed the release of cell-free mitochondrial-DNA, underscoring their indispensable role for mitigating cell damage in bioengineered tissues. Furthermore, their incorporation upregulated the secretion of pro-angiogenic, matrix remodeling and cardioprotective cytokines such as MMP-12, MMP-2, Angiopoietin-like 1, NRG-3, SIGIRR and Adiponectin. RNA sequencing disclosed upregulation of cardiac maturation (TTNI3, SCN5A, MYL2, and RYR2), and endothelial cells genes (PDGF-B, PECAM-1 and CDH5) as well as enhancement of angiogenic signaling, Wnt and PDGF pathways. Collectively, our results offer valuable insights into the integral role of primitive macrophages in directing long-term functional vascularization of cardiac tissues, paving the way for novel therapeutic strategies and advancing heart-on-a-chip systems.
2025-08-04 | PXD044560 | Pride