Transdifferentiation of Fat Cells Into Liver Cells and a Demonstration of Partial Liver Regeneration

This is the age of discovery for cellular control: cells are just complex machines, and with the right environment and chemical instructions the behavior and even type of a cell lineage can be radically changed. A lot of time and funding presently goes into discovering how to achieve these goals, as greater control over cells opens up many new vistas in medicine. At present, and in parallel to research into induced pluripotency as a path to generating any type of cell from easily obtained patient samples, such as skin or fat tissue, scientists are exploring the possibilities of transdifferentiation. At least some types of cell can be coerced into directly becoming other types of cell, without having to pass through an embryonic-like pluripotent stage, and researchers are becoming better at making this happen:

Scientists have developed a fast, efficient way to turn cells extracted from routine liposuction into liver cells. The scientists performed their experiments in mice, but the adipose stem cells they used came from human liposuction aspirates and became human, liver-like cells that flourished inside the mice's bodies.

Liver cells are not something an adipose stem cell normally wants to turn into. The [researchers] knew it was possible, though. Another way of converting liposuction-derived adipose stem cells to liver-like cells had been developed in 2006. But that method, which relies on chemical stimulation, requires 30 days or longer and is inefficient; it could not produce enough material for liver reconstitution. Working with induced pluripotent (iPS) cells takes even longer; they must first be generated from adult cells before they can be converted. Using a different technique [known] as spherical culture [researchers] were able to achieve the conversion within nine days with an efficiency of 37 percent, as opposed to the vastly lower yield obtained with the prior method (12 percent) or using iPS cells.

When they had enough cells, the investigators tested them by injecting them into immune-deficient laboratory mice that accept human grafts. Only the livers of these mice contained an extra gene that would convert the antiviral compound gancyclovir into a potent toxin. When these mice were treated with gancyclovir, their liver cells died off quickly. At this point the investigators injected 5 million [of the newly generated cells] into the mice's livers. Four weeks later, the investigators examined the mice's blood and found the presence of a protein (human serum albumin) that is only produced by human liver cells and was shown to be an accurate proxy for the number of new human liver cells in these experimental mice's livers. The mice's blood had substantial human serum albumin levels, which nearly tripled in the following four weeks. These blood levels correspond with the repopulation of roughly 10-20 percent of the mice's pre-destroyed livers by new human liver tissue.

Blood tests also revealed that the mice's new liver tissue was discharging its waste-filtration responsibility. Examination of the livers themselves showed that the transplanted cells had integrated into the liver, expressed surface markers unique to mature human hepatocytes and produced multi-cell structures required for human bile duct formation.



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