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A Bioprinted Liver Model Featuring Induced Pluripotent Stem Cells

Apr 18, 2016 1:00:33 PM / by Steffen Porwollik

Scientists develop a 3D liver tissue model that better resembles a working organ – by bioprinting layers of three cell types that include hepatic progenitors obtained from induced pluripotent stem cells.

The human liver is an astoundingly large organ with a very complex set of tasks. It weighs in at about 3lbs and filters the blood that comes from the digestive tract, detoxifies chemicals, metabolizes drugs and makes important proteins that help with blood clotting. Its health is of vital importance, quite literally. Sadly, liver disease is on the rise. There are more than 100 different kinds of liver maladies, including viral forms such as hepatitis A, B and C, bacterial diseases, diseases caused by autoimmune disorders, and cancer. Shockingly, fatty liver disease and its chronic conclusion, cirrhosis, both alcohol-related and non-alcohol-related, are found in up to 25% of Americans today.

Modern medical research is struggling to find good in vitro model systems on which to test experimental hypotheses and novel drugs against liver disease. One reason lies in the fact that human liver cells (hepatocytes) quickly lose their liver-specific functions when taken out of their normal environment. Induced pluripotent stem cells (iPSCs) have been investigated for some time as a promising cell source for liver tissue models, and they have been used to generate hepatocyte-like cells in research on liver-stage malaria. However, previous efforts have failed to sustain many liver-specific functions in liver cells created from these iPSCs. A 3D environment resembling the actual liver, including endothelial and mesothelial support cells, was considered to be needed, but too difficult to recreate.

Enter a San Diego team of scientists and their innovative bioprinting technique. The researchers took up the challenge and decided to try to bioprint a mix of three different cell types - induced pluripotent stem cells, adipose-derived stem cells, and umbilical vein endothelial cells - in small hexagonal printing patterns that resembled the in vivo architecture of the liver lobes. They recently reported the impressive results of their efforts. [1]

Utilizing the digital light processing-based 3D bioprinting technique they pioneered, the scientists churned out their microscale liver constructs in seconds. These constructs featured the three cell types layered in synthetic hydrogel matrices. The matrices were formulated to precisely mimic the viscosities that the different cell types would encounter in a living organ. The researchers also identified the developmental phase at which the induced pluripotent cells would most reliably retain liver cell characteristics after printing and found that cells in the hepatic progenitor stage, that is, about 12-14 days after initiation of differentiation, were ideal. After process optimization, 65% of the printed cells were still alive 10 days after printing, only 11% fewer than immediately after the printed structures had been made. Moreover, gene expression studies confirmed a higher production of liver-specific markers than in previous, simpler in vitro liver tissue models. Finally, the researchers measured a higher level of the enzymes produced by the liver to oxidize drugs, so-called CYPs, in their new tricellular model compared to the old ones.

While this progress does not mean that we have found the Holy Grail of printing a viable organ from induced pluripotent stem cells, the obtained results are very far from being chopped liver. They show one of many very promising utilities of iPSCs. We at HemaCare have a variety of stem cell products available for your research, including CD133+ progenitor cells from bone marrow that can differentiate into liver cells and mesenchymal stem cells. Please contact us at (877) 397-3087 if you want to discuss or have any questions about any of our cell- or tissue-based products and services.

Reference

[1] Ma X, Qu X, Zhu W, Li YS, Yuan S, Zhang H et al. Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc Natl Acad Sci USA. 2016 Feb 23;113(8):2206-11.

Topics: Cancer, iPSCs, Stem Cells, Basic Research

Steffen Porwollik

Written by Steffen Porwollik

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