Abstract: FR-PO976
Bioengineering an Organotypic Normal and Diseased Kidney Tubule Array
Session Information
- Bioengineering and Informatics
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Bioengineering and Informatics
- 101 Bioengineering and Informatics
Authors
- Subramanian, Balaji karthick, Brigham and Womens Hospital /Harvard Medical School, Boston, Massachusetts, United States
- Kaya, Oguzhan, Brigham and Womens Hospital /Harvard Medical School, Boston, Massachusetts, United States
- Zhou, Jing, Brigham and Womens Hospital /Harvard Medical School, Boston, Massachusetts, United States
Background
Maintenance of homogenous kidney tubular structures is critical to retain kidney shape and function, and in accordance aberrations in their structures are manifested in disease conditions. Lack of in vitro kidney tubule models that are homogeneous in tissue geometry structures and also emulating aberrations in disease conditions have limited the understanding of their pathology and the therapeutics development.
Methods
Homogenous tubular tissue geometry micropatterns were imprinted in different extracellular matrix combinations as an array using a combination of photolithography and soft lithography techniques. Tubular kidney epithelial cells were then cultured in the3D micro-molded extracellular matrix array and were evaluated for the morphogenic outcomes. Cystic kidney disease emulation was achieved by treatments with cAMP-elevating agents, while for acute kidney injury emulation cisplatin drug treatment was used.
Results
Both mouse and human kidney epithelial cells formed homogeneous tubular structures as defined by the tissue geometry yielding kidney tubular arrays. The tubule features in the array were validated based on the characteristic distributionof actin (f-actin), cilia (acetylated tubulin),tight junction (ZO-1), and Na+K+-ATPasepump. Further, the disease emulations of cystic kidney disease and acute kidney injury were confirmed for tubule to cyst transformation and Kidney injury molecule (Kim-1) expression respectively.
Conclusion
The tubule array yielded organotypic homogenous tubules with in vivo- scale dimensions, which can be utilized for assessing nephrotoxicity of drugs and the mechanistic studies of various tubular kidney disease, making it an alternative to animal studies.