Biology subjects

Uzel, S. G. M.

Publications and source records attributed to Uzel, S. G. M..

3 recordsLinked to original sources

bioRxiv2025

Perfusable 3D models of ureteric bud and collecting duct tubules

Recent protocols have emerged to derive ureteric bud (UB) and collecting duct (CD) organoids directly from human induced pluripotent stem cells (hiPSCs). However, these 3D kidney tissues lack biophysical cues from luminal flow and a drainage outlet. To address these limitations, we have created perfusable 3D models of UB and CD tubules. UB organoids are first generated from hiPSCs followed by their dissociation into individual UB cells. Individual UB cells are then seeded onto a 3D perfusable channel embedded within an extracellular matrix composed of fragmented basement membrane matrix and collagen I, where they self-assemble into a confluent monolayer. During in vitro perfusion, these cells exhibit UB-like marker expression over several weeks, during which they undergo budding akin to early branching morphogenesis in developing kidneys. To further promote network formation, UB cells are bioprinted adjacent to a perfusable UB tubule, which form interconnections through luminal fusion. Finally, these 3D perfusable UB tubules are differentiated into collecting duct tubules under luminal flow. Our platform facilitates fundamental understanding of human collecting duct formation during renal development, while paving the way for using these physiologically relevant models for drug testing, disease modeling, and, ultimately, integration into bioprinted kidney tissues for therapeutic use.

bioengineering↗

bioRxiv2024

Embedding biomimetic vascular networks via coaxial sacrificial writing into functional tissue

Printing human tissue constructs replete with biomimetic vascular networks is of growing interest for tissue and organ engineering. While it is now possible to embed perfusable channels within acellular and densely cellular matrices, they lack either the branching or multilayer architecture of native vessels. Here, we report a generalizable method for printing hierarchical branching vascular networks within soft and living matrices. We embed biomimetic vessels into granular hydrogel matrices via coaxial embedded printing (co-EMB3DP) as well as into bulk cardiac tissues via coaxial sacrificial writing into functional tissues (co-SWIFT). Each method relies on an extended core-shell printhead that promote facile interconnections between printed branching vessels. Though careful optimization of multiple core-shell inks and matrices, we show that embedded biomimetic vessels can be coaxially printed, which possess a smooth muscle cell-laden shell that surrounds perfusable lumens. Upon seeding these vessels with a confluent layer of endothelial cells, they exhibit good barrier function. As a final demonstration, we construct biomimetic vascularized cardiac tissues composed of a densely cellular matrix of cardiac spheroids derived from human induced pluripotent stem cells. Importantly, these co-SWIFT cardiac tissues mature under perfusion, beat synchronously, and exhibit a cardio-effective drug response in vitro. This advance opens new avenues for the scalable biomanufacturing of organ-specific tissues for drug testing, disease modeling, and therapeutic use.

bioengineering↗

bioRxiv2023

Immune Response of Transplanted Kidney Tissues Assembled from Organoid Building Blocks

The increasing scarcity of organs and the significant morbidity linked to dialysis requires the development of engineered kidney tissues from human-induced pluripotent stem cells. To accomplish this, integrative approaches that synergize scalable kidney organoid differentiation, tissue biomanufacturing, and comprehensive assessment of their immune response and host integration are essential. Here, we create engineered human kidney tissues composed of kidney organoid building blocks (OBBs) and transplant them into mice reconstituted with allogeneic human immune cells. We assess their host vascular integration, in vivo maturation, and their ability to trigger human immune responses. Tissue-infiltrating human immune cells are composed of effector T cells and innate cells. This immune infiltration leads to kidney tissue injury characterized by reduced microvasculature, enhanced kidney cell apoptosis, and a unique inflammatory gene signature comparable to kidney organ transplant rejection in humans. Upon treatment with the immunosuppressive agent Rapamycin, the induced immune response is greatly suppressed. Our model serves as a translational platform to study engineered kidney tissue immunogenicity and develop novel therapeutic targets for kidney rejection.

bioengineering↗