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TELi: A New Treatment Strategy for Liver Disease?

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Review of ““Functional Human and Murine Tissue-Engineered Liver Is Generated From Adult Stem/Progenitor Cells” from Stem Cells Translational Medicine by Stuart P. Atkinson

While end-stage liver failure currently necessitates whole liver transplantation, metabolic liver disorders can be treated via the transplantation of smaller liver segments. However, large or small, healthy livers still remain scarce.

In an attempt to solve this problem, researchers from the team of Tracy Grikscheit (Children’s Hospital Los Angeles, USA) have applied their knowledge regarding the generation of tissue-engineered intestines (TEIs) from adult stem cell populations to the liver, to produce functional tissue-engineered liver (TELi). Now, in a new Stem Cells Translational Medicine article, the authors describe their recent findings into what could represent an effective new treatment strategy for liver disease [1].

The study began in a mouse model, where the authors removed small amounts of liver to extract what they termed as liver organoid units (LOUs) composed of multiple liver cell types including adult stem and progenitor cells. Implantation of LOUs as part of a biodegradable scaffold under the abdominal skin of mouse donors allowed the formation of TELi which, while being organizationally dissimilar to native liver, contained key liver cell types and expressed desired marker proteins. The authors experienced similar success implanting human LOUs generated from liver tissue discarded during surgical procedures into mouse donors, generating functional liver tissues which secreted human albumin.

So far so good! Seemingly functional human and mouse TELi, but can they be employed to treat metabolic diseases? To assess this, the authors implanted LOUs into mice with a lethal form of arginase deficiency and discovered that implanted mice survived longer, cells within the TELi proliferated, and the growing TELi contributed towards hepatic function!

The authors note that their TELi approach features several advantages above and beyond other liver replacement strategies including improved accessibility allowing stricter monitoring, minimized cell loss, and durable function, and so may represent effective new treatment strategy for liver disease. 

The question now is which organ will the Grikscheit lab choose next?! Stay tuned to the Stem Cells Portal and Stem Cells Translational Medicine to find out!

References

  1. Mavila N, Trecartin A, Spurrier R, et al. Functional Human and Murine Tissue-Engineered Liver Is Generated from Adult Stem/Progenitor Cells. STEM CELLS Translational Medicine 2017;6:238-248.