July 5, 2013
Co-Author: Andrew Mullins
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 were induced to form from the iPS cells, while the other cells were used to form support tissue including cells for blood vessels. In the laboratory, the 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, and the mice will be observed for some time to come to observe whether iPS cells, since they behave like embryonic stem cells, create tumors in the animals. 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, 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 use for 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.
Another route to liver regeneration involves injecting adult stem cells into damaged liver tissue, stimulating regrowth 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. Non-embryonic stem cells continue to lead the way in the lab, as well as in the clinic.