Human embryonic stem cells (hESCs) hold great promise for regenerative medicine because of their properties of self-renewal and differentiation into any specialized cell types. However, for the treatment of liver diseases using stem-cell derived hepatocytes, there are still major challenges that must be overcome before these cells can be used for therapeutic applications. For the large quantities of cells required for hepatic applications, a more efficient method of deriving and culturing stem-cell derived hepatocytes will be needed in the near future. In addition to the cell yield, the functional maturity of the cells will depend largely upon a controllable and robust culture environment that can favor the expansion and differentiation of stem cells.<br/>The focus of this study was to translate our previously devised method of differentiating hepatocyte-like cells into a scalable system more suited for industrial and clinical settings. This approach was shown using microcarriers beads to illustrate the expansive and differentiation capability of the endodermal cells in a static environment. Using our conventional method of differentiation, we were able to utilize a cell in a stage that was capable of differentiating and expanding to generate a robust scalable bioprocess for generating enough cells for effective use in the various clinical applications. The quality of hepatocyte-like cells was comparable to the static cultures in terms of hepatic transcript expression and functional maturity. Furthermore, high cell concentrations on these microcarrier beads in a controlled bioreactor will allow us to venture into the dynamics of the metabolism of the cells during our hepatocyte differentiation. Thus, this robust system provides us with a simple scalable process for the generation of large quantities of stem-cell derived hepatocytes to cater to various applications in the near future.

Scalable hepatic differentiation of human endodermal cells from pluripotent stem cell

251st National Meeting (2016)

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