Vascularization of Human iPSC-Derived Kidney Organoids Using Perfusion Culture, Pre-Vascularized Collagen Scaffolds, and Decellularized Extracellular Matrix.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Human induced pluripotent stem cell-derived kidney organoids represent promising in vitro models for studying kidney development and drug-induced toxicity, yet their lack of vasculature limits maturation and translational use. Here, we present a proof-of-concept co-culture platform to promote vascularization of kidney organoids by integrating stromal vascular fraction cells, collagen sponge scaffolds, porcine kidney decellularized extracellular matrix (dECM), and dynamic culture in a perfusion-based U-CUP bioreactor. We systematically evaluated the effects of serum supplementation, scaffold pre-vascularization, dECM encapsulation, and flow conditions on organoid-vascular integration. Low-level serum supplementation (1.5% FBS) sustained vascular networks without compromising organoid morphology. Perfusion supported vascular expansion; however, while a low flow rate comparable to interstitial tissue flow (0.01 mL/min) preserved organoid morphology and glomerular-like structures, a higher flow rate optimized for vascularization (0.47 mL/min) disrupted overall organoid architecture. Encapsulation within dECM preserved glomerular morphology and supported vascular infiltration, whereas co-culture with stromal vascular fraction cells enabled putative podocyte-endothelial interactions. Finally, exposure to the calcineurin inhibitor tacrolimus revealed dose-dependent cytotoxicity and ch

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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