Abstract: SA-OR071
Engineered Flow Dynamics Drive Vascular and Pathological Features in Kidney Organoids
Session Information
- Innovations in Pediatric Nephrology and Kidney Development
November 08, 2025 | Location: Room 371A, Convention Center
Abstract Time: 05:40 PM - 05:50 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 600 Development, Stem Cells, and Regenerative Medicine
Authors
- Higashi, Yuhei, Massachusetts General Hospital, Boston, Massachusetts, United States
- Kuraoka, Shohei, Massachusetts General Hospital, Boston, Massachusetts, United States
- Honjoh, Honami, Massachusetts General Hospital, Boston, Massachusetts, United States
- Morizane, Ryuji, Massachusetts General Hospital, Boston, Massachusetts, United States
Background
Kidney organoids derived from stem cells are powerful tools for studying kidney development and hereditary diseases. Integration with organoid-on-a-chip systems has shown promise in inducing vascularization and modeling disease; however, the specific role of flow dynamics in these processes remains poorly defined. Here, we developed a new kidney organoid-on-a-chip platform with programmable perfusion capability that enables precise control of flow profiles—specifically, continuous vs pulsatile flow—to investigate how mechanical cues affect organoid maturation, glomerular vascularization, and disease phenotypes.
Methods
Day 14 nephron organoids were placed in microfluidic chips containing extracellular matrix-enriched medium and subjected to either continuous or pulsatile flow using a custom-designed perfusion pump capable of replicating arterial-like pressure waves. After three weeks (day 35), organoids were analyzed by live imaging and whole-mount immunostaining.
Results
Pulsatile flow, mimicking arterial blood pulse, significantly enhanced the formation of a perfusable vascular network, including robust microvascular invasion into glomeruli—an outcome not achieved with continuous flow. Perfusability was confirmed by 3-kDa dextran tracer perfusion reaching tubular structures within 30 minutes. In a polycystic kidney disease (PKD) organoid model, pulsatile flow alone was sufficient to induce cystogenesis from CDH1-positive distal tubules without pharmacological stimulation, resembling the ARPKD phenotype. Transcriptomic analysis revealed upregulation of cAMP signaling under pulsatile conditions, suggesting that biomechanical stimulation alone can recapitulate pathophysiologic signaling. These findings highlight the importance of physiologic flow patterns—particularly pulsatility—in orchestrating vascular maturation and disease modeling in kidney organoids.
Conclusion
Our newly developed perfusion-controlled organoid-on-a-chip system reveals that arterial-like pulsatile flow is a key driver of glomerular vascularization and disease-relevant phenotypes. This platform offers a physiologically relevant niche for advancing studies in kidney development, vascular integration, and in vitro disease modeling, with broad potential for drug testing and regenerative medicine.
Funding
- NIDDK Support