Myofibroblasts of bone marrow origin have recently been found in a number of parenchymal organs such as the gut and kidney.
In this study, investigators from England and Italy analyzed the origin of myofibroblasts within fibrotic livers.
The team looked at 2 scenarios. The first included 7 male patients who had received liver transplants from female donors and subsequently developed liver fibrosis. The second included a female patient who received a bone marrow transplant from a male donor and developed hepatitis C-induced cirrhosis.
The investigators used in situ hybridization for the Y chromosome to track male cells of extrahepatic origin.
|In the bone marrow recipient, 12% of the myofibroblasts were of bone marrow origin.|
The team examined the phenotype of these cells using immunohistochemistry. They used a panel of antibodies against alpha-smooth muscle actin (alpha-SMA), vimentin, fibulin-2, and leukocyte common antigen (CD45).
They also performed confocal microscopy to confirm the location of the Y chromosome probe within the myofibroblast nuclei.
The investigators found that significant numbers of Y chromosome-positive cells in fibrotic areas were found to be positive for alpha-SMA, vimentin, and fibulin-2 and negative for CD45. Thus having a myofibroblast phenotype.
The team established that, in the liver transplant cases, 7% to 22% of alpha-SMA-positive myofibroblasts contained the Y chromosome.
In addition, the team found that in the bone marrow recipient, 12% of the myofibroblasts were Y chromosome positive, indicating a bone marrow origin.
Dr Stuart Forbes's team concluded, "There is a significant contribution to liver cirrhosis in humans from extrahepatically derived myofibroblasts in liver disease of diverse etiology".