Human liver or hepatocyte transplantation is constrained by a severe shortage of donor organs. Creative Bioarray has been focused on developing multiple cell reprogramming strategies to reprogram other adult cells into hepatocytes to help researchers address bottlenecks in clinical applications and research.
Introduction
Liver failure is a life-threatening disease and one of the most common causes of mortality. Whole or assisted partial liver transplantation is usually the only available treatment option for liver failure or disorders of liver metabolism. Moreover, the severe shortage of suitable organs and the risks accompanying major surgery make liver transplantation an expensive and complex treatment option. Numerous studies have shown that hepatocyte transplantation in rodents can reverse liver failure, suggesting that hepatocyte transplantation is a hopeful alternative to whole-organ transplantation. Therefore, the generation of functional and scalable human hepatocytes independent of the donor organs in vitro has attracted the interest of many investigators.
Human hepatocytes can be produced from human embryonic stem cells (hESC) or iPSC. However, the use of hESC-derived hepatocyte-like cells faces thorny issues including ethics and possible immune rejection. Report of successful reprogramming of epithelial cells from urine into iPSCs have laid the experimental foundation for the directed differentiation of iPSC derived from urinary cells into hepatocyte-like cells. In addition, direct reprogramming techniques that reprogram one somatic cell type into another desired cell type without going through a pluripotent state provide a new approach to generate functional and expandable human hepatocytes.
Fig.1 Experimental design for the generation of expandable hepatocyte-like cells from human urine-derived epithelial-like cells. (Tang, 2019)
Our Strategies
Over the years, Creative Bioarray has made great progress in inducing the differentiation of pluripotent stem cells into hepatocytes and in directly reprogramming other cell lineages into hepatocytes. We offer a variety of cell reprogramming strategies for our clients to choose the best solution.
- Human urinary epithelial cells were reprogrammed into iPSCs by delivering pluripotent factors OCT3/4, KLF4, Sox2, and MYC using strategies without transgene integration. After characterizing stable iPSC lines, multi-step differentiation was performed to obtain hepatocytes.
- Transformation of human urinary epithelial cells into induced hepatocyte-like cells by overexpression of liver-specific transcription factors including HNF1α, FOXA3, and GATA4.
- Direct transformation of human urinary-derived epithelial-like cells into hiHeps by combining chemical cocktail CRVPTD (CHIR99021, RepSox, VPA, Parnate, TTNPB, and Dznep) with one transcription factor (Foxa3, Hnf1α or Hnf4α).
Applications
- Disease modeling
- Pharmacological testing
- Hepatocyte transplantation-based regenerative medicine
Advantages
- Non-invasive isolation
- Simple cell culture technique
- Efficient cell reprogramming platform
Over the years, Creative Bioarray has been committed to developing a first-class cell reprogramming platform to provide customers with a wide range of reprogramming services. We have been successful in helping our customers generate human hepatocyte-like cells from urine, and the obtained cells have been proved to express hepatocyte-specific genes with various mature hepatocyte functions. If you need our services, please contact us directly.
References
- Tang, W.; et al. Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor. Acta pharmacologica Sinica. 2019, 40(5): 620-629.
- Wu, H.; et al. Generation of hepatocyte-like cells from human urinary epithelial cells and the role of autophagy during direct reprogramming. Biochemical and Biophysical Research Communications. 2020, 527(3): 723-729.