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Abstract: TH-PO632

Directed Differentiation of Functional Kidney Cells from Human Induced Pluripotent Stem Cells

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 501 Development, Stem Cells, and Regenerative Medicine: Basic

Author

  • Musah, Samira, Harvard University, Boston, Massachusetts, United States
Background

Many diseases and drugs affect kidney function by damaging the glomeruli, which serve as the functional units of the kidney and the center for blood filtration. An in vitro model of human glomerulus could facilitate therapeutic discovery and illuminate kidney disease mechanisms. Efforts to develop such models are hindered by the lack of functional human podocytes, the specialized epithelial cells that regulate selective permeability in the glomerulus. Human pluripotent stem (hPS) cells have a remarkable capacity to self-renew indefinitely and differentiate into almost any cell type under appropriate conditions. Thus, hPS cells could potentially serve as an unlimited source of podocytes; however, a method for directing their differentiation into glomerular podocytes remains elusive.

Methods

We hypothesized that a systematic investigation of multiple factors within the cellular microenvironment -- including cell-cell interactions, soluble signaling molecules, and mechanical properties of the extracellular matrix (ECM) -- could yield an effective method for podocyte differentiation.

Results

By following this principle, we developed a highly efficient method for differentiation of hPS cells into podocytes. The hPS-derived podocytes express markers consistent with mature phenotype and exhibit primary and secondary foot processes. By using Organ Chip microfluidic devices, we developed an in vitro model of the human glomerular capillary wall that supports podocyte differentiation and recapitulate the normal tissue-tissue interface and selective permeability of the glomerulus.

Conclusion

Our results demonstrate the feasibility of generating mature podocytes in a robust manner, providing an opportunity to engineer a functional human kidney model. These results could facilitate investigations to illuminate developmentally regulated events in kidney pathophysiology, and provide a low cost alternative to animal models for the development of therapeutics for human kidney disease. As podocytes are unable to undergo regenerative proliferation in vivo, these results also provide opportunities for cell therapy and regenerative medicine.

Funding

  • NIDDK Support