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Translating Regenerative Surgery on the Liver From Concept to Therapeutic Reality

Tissue engineering and regeneration are the next evolutionary step in surgical practice. As surgeons, we resect, reconstruct, and transplant to treat a diverse array of diseases resulting from acute inflammation, congenital malformation, malignancy, or organ failure. In the near future, our armamentarium will increase to include using our surgical skills to induce tissue regeneration in situ or to implant ex vivo engineered organs. Accelerating advances in biotechnology, stem cell biology, and minimally invasive surgery are ripe for convergence, which will lead to the creation of novel surgical treatments to replace diseased or dysfunctional tissues. Our lab's goal is to make significant contributions to bringing these regenerative surgical therapies from the lab into the operating room.

In order to translate regenerative surgery from concept to therapeutic reality, our lab focuses on a complex and vital solid organ, the liver, for several reasons. First, there is great clinical need to develop alternative therapies for end stage liver disease, which is currently treated by liver transplantation and severely limited by the shortage of donor organs. Second, the liver has enormous innate capacity to regenerate in response to injury and metabolic demand, a feature that can be exploited to facilitate development of regenerative surgical approaches. Finally, building a solid organ such as the liver ex vivo remains the most challenging goal in tissue engineering and a problem of sufficient difficulty that is worthy of a lifetime’s work.

Our lab has 3 major areas of investigation aimed at advancing the field of liver tissue engineering:

  • Understanding the role of the physical environment and mechano-signal transduction in regulating hepatocyte function in healthy and diseased liver.
  • Elucidating the importance of dimensionality in promoting the generation of highly-functional human stem cell-derived liver organoids.
  • Developing surgical strategies for efficient orthotopic engraftment of hepatocytes and hepatic organoids into the liver.

Latest News

Our lab has reported on generating human induced pluripotent stem cell (iPSC)-derived liver organoids using microgravity culture conditions that induce tissue self-assembly. Microgravity self-assembled liver organoids are more highly differentiated and functional compared to organoids generated by current prevailing approaches that rely on a mouse cell-line-derived extracellular matrix. Moreover, microgravity self-assembled organoids are promising for clinical translation towards stem-cell-based human tissue replacement therapy and supports the development of larger bioengineered tissue constructs in space.

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