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Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent
Kazuki Takeishi1, Alexandra Collin de l'Hortet2, Yang Wang3
1Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Cell Reports
|June 4, 2020
Summary
Researchers engineered functional human mini livers using induced pluripotent stem cells (iPSCs) and successfully transplanted them into rats. This breakthrough offers potential for treating liver disease with bioengineered organs.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Bioengineering
Background:
- Autologous transplantable livers could revolutionize liver disease treatment.
- Previous bioengineered liver studies have not demonstrated in vivo assembly and function using human induced pluripotent stem cells (iPSCs).
Purpose of the Study:
- To generate functional, bioengineered human mini livers from iPSCs for transplantation.
- To demonstrate the in vivo assembly and function of a multi-cellular, iPSC-derived human liver.
Main Methods:
- Improved liver decellularization, recellularization, and iPSC differentiation techniques were employed.
- Human iPSC-derived hepatocytes, endothelial cells, and biliary epithelial cells were used to repopulate liver scaffolds.
- Auxiliary liver transplantation was performed in immunocompromised rats (IL2rg-/-).
Main Results:
- Functional engineered human mini livers were generated using iPSCs.
- The bioengineered liver contained multiple human cell types, including hepatocytes, endothelial, and biliary cells.
- The transplanted mini liver remained functional in vivo for 4 days.
Conclusions:
- This study demonstrates the successful in vivo assembly and function of a bioengineered human liver derived from iPSCs.
- The multi-cellular repopulation strategy is crucial for creating functional engineered organs.
- This work represents a significant step towards developing iPSC-based therapies for liver disease.
