Date: 01 Jul 2013
Critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from pluripotent stem cells. Despite many reports describing functional “cell” differentiation, no studies have succeeded in generating a three-dimensional vascularized “organ” such as liver so far.
Takanori Takebe and Hideki Taniguchi at Yokohama City University showed the generation of vascularized and functional human liver from human induced pluripotent stem cells (hiPSCs) by transplantation of in vitro grown liver buds (rudimentary liver). This study demonstrates a proof-of-concept that organ bud transplantation offers an alternative approach for treating organ failure by generating a 3D and vascularized organ.
This study was published in the journal Nature (6 pm London time Wednesday 3rd July ) .
Nature 499, 481–484 (25 July 2013) doi:10.1038/nature12271
This work was supported by grants to H. Taniguchi from Strategic Promotion of Innovative Research and Development (S-innovation, 09158881) from Japan Science and Technology Agency (JST). This work was also supported by grants to T. Takebe from Grant-in-Aid for Scientific Research on Innovative Areas (No. 24106510) and Grant-in-Aid for Young Scientists (A) (24689052) by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Background and results
Since the discovery of embryonic stem cells in1981, decades of laboratory studies have failed to generate a complex vascularized organ such as liver from pluripotent stem cells (PSCs), giving rise to the prevailing belief that in vitro recapitulation of the complex interactions among cells and tissues during organogenesis is considered to be essentially impractical. Here, we challenge this notion by focusing on the earliest process of organogenesis, i.e. cellular interactions during “organ bud” development.
Manipulation of iPSCs holds great promise for regenerative medicine. However, clinical trials of “cell transplantation”, that is a current main target of stem cell-based approach, have presented unsatisfactory results. Our study demonstrates a proof-of-concept that “organ bud transplantation” offers an alternative approach resulting in the generation of a 3D, vascularized organ. These results highlight the enormous therapeutic potential using in vitro grown organ bud transplantation for treating organ failure.
The liver is significantly active in metabolizing compounds and the major target for toxicity caused by drugs. Liver toxicity and alterations of hepatic physiology are frequently occurring reasons for preclinical failure during drug development. Prioritization of compounds based on human hepatotoxicity potential is currently a key unmet need in drug discovery. Current hepatocyte model systems include primary human hepatocytes harvested from cadavers, immortalized cell lines, hiPSC-derived hepatocyte-like cells and animal models. However, each of these model systems presents limitations in functionality, reproducibility, and/or availability. Our results represent the potential for predicting humanized profile of drug metabolism mimicking in vivo human physiology. Fully functioning hepatocytes differentiated from hiPSCs in liver bud will aid to assess the drug safety and efficacy for preclinical drug discovery, hepatotoxicity testing, and disease research.
For inquiries regarding this press release
Hideki Taniguchi, Takanori Takebe
Yokohama City University Department of Regenerative Medicine
Phone: +81-45-787-2621; FAX: +81-45-787-8963
E-mail : firstname.lastname@example.org (Taniguchi)