Abstract: FR-PO976

Bioengineering an Organotypic Normal and Diseased Kidney Tubule Array

Session Information

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.