Transplanting cells from healthy adult livers may work in treating a genetic liver-lung disorder that affects millions of people worldwide, a mice study revealed.
The genetic disorder, alpha-1 antitrypsin (AAT) deficiency, is the most common potentially lethal hereditary disease among Caucasians. AAT is a protein made by the liver that is essential for lung health. In AAT deficiency, the liver produces a misshapen form of AAT that cannot enter the bloodstream and instead gets stuck inside liver cells, causing two major problems - fibrosis (development of scar tissue) and liver failure.
Too little AAT reaches the lungs, where it's needed to rein in elastase, an enzyme produced by white blood cells. Elastase helps kill bacteria in the lungs, but uncontrolled elastase activity can damage lung tissue and lead to severe emphysema (chronic obstructive pulmonary disease).
In the study, Jayanta Roy-Chowdhury, professor of medicine and of genetics at Albert Einstein College of Medicine of Yeshiva University, and his colleagues tested cell therapy on transgenic mice whose liver cells (hepatocytes) had been engineered to produce mutant human AAT, resulting in liver fibrosis. When the mice were given infusions of hepatocytes harvested from the livers of healthy mice, the transplanted cells proliferated in the host liver, progressively replacing diseased hepatocytes.
Most importantly, the transplanted cells reversed the fibrosis that had developed, said Roy-Chowdhury
"These promising results in animals indicate that it may be worthwhile to investigate the usefulness of hepatocyte transplantation for AAT deficiency as well as a variety of other inherited liver-based disorders," said Roy-Chowdhury.
The study has been published in the Journal of Clinical Investigation.