Renal reabsorption in 3D vascularized proximal tubule models

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Renal Physiology

Background:

• Developing functional three-dimensional (3D) kidney tissues is crucial for understanding kidney physiology and disease.
• Existing models often lack the complex cellular composition, geometry, and vascularization of native renal tissue.

Purpose of the Study:

• To create a 3D vascularized proximal tubule model that emulates native kidney tissue for studying renal reabsorption.
• To investigate tubular-vascular exchange of solutes and epithelium-endothelium cross-talk in vitro.
• To establish a platform for kidney disease modeling and pharmacological testing.

Main Methods:

• Constructed 3D renal tissues with adjacent conduits lined by confluent epithelium and endothelium within a permeable extracellular matrix (ECM).
• Utilized a closed-loop perfusion system for independent addressing of tissue components.
• Quantified albumin uptake and glucose reabsorption over time.
• Induced hyperglycemic conditions to study proximal tubule cell and endothelial cell dysfunction.

Main Results:

• The 3D kidney tissue model demonstrated active reabsorption via tubular-vascular exchange, mimicking native kidney function.
• Albumin uptake and glucose reabsorption were successfully quantified over time.
• Epithelium-endothelium cross-talk was observed, leading to endothelial cell dysfunction under hyperglycemic conditions.
• Administration of a glucose transport inhibitor rescued the diseased state.

Conclusions:

• The developed 3D vascularized proximal tubule model serves as a valuable platform for in vitro studies of kidney function.
• This model facilitates the investigation of renal reabsorption, tubular-vascular exchange, and kidney disease mechanisms.
• The platform is suitable for preclinical drug screening and evaluating therapeutic interventions for kidney diseases.