In recent years some progress has been made towards the distinct goals of complete regeneration of a damaged liver in situ and the creation of new livers on demand for transplantation. Here, researchers demonstrate the ability to generate a patient-matched source of liver cells for repair purposes:
In previous studies on liver-cell reprogramming, scientists had difficulty getting stem cell-derived liver cells to survive once being transplanted into existing liver tissue. Writing in the latest issue of the journal Nature, researchers reveal a new cellular reprogramming method that transforms human skin cells into liver cells that are virtually indistinguishable from the cells that make up native liver tissue.
"Earlier studies tried to reprogram skin cells back into a pluripotent, stem cell-like state in order to then grow liver cells. However, generating these so-called induced pluripotent stem cells, or iPS cells, and then transforming them into liver cells wasn't always resulting in complete transformation. So we thought that, rather than taking these skin cells all the way back to a pluripotent, stem cell-like state, perhaps we could take them to an intermediate phase."
This research [involved] using a 'cocktail' of reprogramming genes and chemical compounds to transform human skin cells into cells that resembled the endoderm. Endoderm cells are cells that eventually mature into many of the body's major organs - including the liver. Next, the researchers discovered a set of genes and compounds that can transform these cells into functioning liver cells. And after just a few weeks, the team began to notice a transformation. Now that the team was encouraged by these initial results in a dish, they wanted to see what would happen in an actual liver. So, they transplanted these early-stage liver cells into the livers of mice. Over a period of nine months, the team monitored cell function and growth by measuring levels of liver-specific proteins and genes.
Two months post-transplantation, the team noticed a boost in human liver protein levels in the mice, an indication that the transplanted cells were becoming mature, functional liver cells. Nine months later, cell growth had shown no signs of slowing down. These results indicate that the researchers have found the factors required to successfully regenerate liver tissue.