GROWING HUMAN LIVER TISSUE FROM IPS CELLS

By David Prentice and Andrew Mullins

Editor’s note. iPS cells (induced pluripotent stem cells) are made by adding a few genes to a normal cell such as a skin cell, causing the normal cell to look and act like an embryonic stem cell, yet without use of embryos, eggs, or cloning technology. They are not “adult stem cells,” but rather an ethically derived version of embryonic stem cells.

Prof. Colin McGuckin (front) and Dr Nico Forraz

Prof. Colin McGuckin (front) and Dr Nico Forraz

Japanese scientists have succeeded in growing chunks of functional human liver tissue in mice. The research, published in the journal Nature, constructed the human liver tissue using a combination of three cell types: induced pluripotent stem cells (iPS cells), human umbilical cord blood stem cells, and bone marrow mesenchymal stem cells.

The liver cells in the newly-constructed tissue were made from iPS cells, while the other cell types were used to form support tissue including cells for blood vessels. In the laboratory, the different cells organized themselves into pieces of tissue, termed “liver buds.” When transplanted into mice, the “liver buds” showed some specific liver function, and also hooked into the circulatory system, allowing the liver tissue to survive and continue growing. The functional human liver tissue was also able to rescue mice from liver failure.

It’s still early in the study and development of iPS cell-derived tissues and organs. Since iPS cells behave like embryonic stem cells and have created tumors in animals, the mice will be observed for some time to come. Still, it’s a significant step forward for potential use of iPS tissues in laboratory studies, and a novel way to produce organ rudiments.

Back in 2006, Prof. Colin McGuckin’s lab showed that they could grow pieces of liver tissue in the laboratory, starting with human umbilical cord blood stem cells. The adult stem cells found in umbilical cord blood, as well as the solid umbilical cord, appear to be very flexible in their potential to grow various tissues.

In 2010, Wake Forest scientists showed that they could construct miniature human livers in the laboratory using adult precursor cells. That research technique differs from the new report for iPS cell-derived liver.

The Wake Forest group started by stripping the cells off of normal liver tissue, forming “decellularized scaffolds” to which cells normally attach in an organ and which give an organ structure. The decellularized scaffold consist of extracellular matrix, including the proteins and other biomolecules on which cells hang in an organ and which can affect cell differentiation within that tissue. That matrix was then seeded with human liver precursor cells and human endothelial cells (which line and help create blood vessels.) The remade liver construct was grown in a bioreactor in the lab, and after a week demonstrated human liver tissue growth and function.

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Another route to liver regeneration involves injecting adult stem cells into damaged liver tissue, stimulating re-growth of liver tissue. The technique has been used in limited clinical trials but has shown some success for adult stem cell regeneration of liver in patients.

Both techniques were recently reviewed by the Wake Forest group, as well as in-depth description of the decellularization method for liver construction.

So despite all the hype about embryonic stem cells creating new tissues and treating disease, it is instead still non-embryonic stem cells (that is, adult stem cells and iPS cells) that continue to lead the way in the lab, as well as in the clinic.

Editor’s note. This first appeared in a slightly different form at frcblog.com.