New method for high-volume production of engineered gut and liver tissue

Researchers from Cincinnati Children’s Center for Stem Cell and Organoid Medicine and Yokohama City University have devised a two-step method for producing tissue that could reduce tumorigenesis risk.

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Feb 12, 2018
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In new research published in Stem Cell Reports, international researchers have developed a new method that could enable the manufacture of large volumes of transplantable tissue that is free from the risk of tumor growth. Scientists from the Cincinnati Children’s Center for Stem Cell and Organoid Medicine (OH, USA) and Yokohama City University (Japan) utilized a multi-step process to grow organoids from induced pluripotent stem cell (iPSC)-derived posterior gut endodermal progenitor cells (PGECs).

“Compared to gastrointestinal organoids and liver-generated directly from induced pluripotent stem cells, generation from PGECs resulted in robust and genetically stable formation of different tissue GI types, without causing benign tumors called teratomas,” commented first author Ran-Ran Zhang, (Cincinnati Children’s).

“Our data also show liver organoids grown from PGECs and transplanted into immunodeficient mice with liver disease grew, functioned well and prevented liver failure.”

The iPSCs were transformed into CDX2-positive PGECs using the genes FGF, TGF and WNT, with further manipulations used to encourage development of the PGECs into human hindgut and liver organoids. Unlike previous studies, the organoids were developed in this work without any animal bioproducts. In addition, the PGECs multiplied their numbers by 1012 after 20 re-plates. Therefore, it’s feasible that this technique could create enough tissue, and suitable tissue, for eventual transplantation.

The team will continue to refine the method, with a focus on liver organoids. Lead author Takanori Takebe also commented that they are preparing for a clinical trial involved the human transplantation of a bioengineered liver.

Sources: Zhang R-R, Koido M, Tadokoro T, Ouchi R, Matsuno T, Ueno Y et al.  Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids. doi: 10.1016/j.stemcr.2018.01.006 (2018)(ePub ahead of print); https://www.cincinnatichildrens.org/news/release/2018/bioengineered-organs

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