Tissue-engineered three-dimensional in vitro models for normal and diseased kidney.

Area of Science:

• Biomaterials science
• Tissue engineering
• Renal physiology

Background:

• Epithelial cell morphogenesis regulates kidney structure and function.
• Existing in vitro models lack sustainability and fail to capture complex kidney cell interactions, limiting research into diseases like autosomal dominant polycystic kidney disease (ADPKD).

Purpose of the Study:

• To develop a sustainable three-dimensional (3D) coculture system for normal and ADPKD kidney tissues.
• To create an in vitro model that emulates kidney tissue morphogenesis and intercellular interactions for disease research and drug screening.

Main Methods:

• Culturing normal and ADPKD kidney cells within extracellular matrix-infused 3D porous silk scaffolds.
• Integrating these cultures into a perfusion bioreactor system for extended culture.
• Utilizing collagen-matrigel for cell culture and supporting fibroblast coculture.

Main Results:

• Demonstrated collagen-matrigel-mediated morphogenesis for both normal and ADPKD kidney cells.
• Validated structural and functional integrity of engineered kidney tissues using specific markers (E-cadherin, N-cadherin, Na+ K+ ATPase, 6-carboxy fluorescein uptake).
• Successfully sustained engineered tissues in a perfusion bioreactor for extended periods.

Conclusions:

• The developed 3D in vitro coculture system provides a sustainable platform for studying kidney morphogenesis and ADPKD.
• This model shows potential for advancing ADPKD research, investigating other epithelial systems, and enabling in vitro drug screening.