An Immunohistochemical Study of c-kit⁺CD34⁺cells in Severe Liver Damage

Abstract

The role of hepatic stem cells in liver regeneration following severe liver damage was studied by immunohistochemistry. Hepatobiopsy specimens were obtained from 16 patients with a serious liver disorder and c-kit ⁺CD34⁺ cells were counted following immunostaining with antibodies against c-kit and CD34. The liver was spatially divided into affected and non-affected areas ; the affected area was further segmented into central and border areas. The temporal and spatial appearance of the c-kit ⁺ CD34⁺ cells in the liver was assessed, as well as the relationship of these cells with CK 19-positive bile ducts. The c-kit⁺CD34⁺cells appeared soon after onset of the liver disorder, and independently of the underlying disease in all patients. Regardless of time after onset of the liver disorder, the number of c-kit⁺CD34⁺cells was high in the affected areas. The appearance rate tended to be high in the central affected areas in the early stages of damage, and high in the border affected areas at the later stages of the disorder. The absolute number of c-kit⁺CD34⁺ cells appeared to be smaller in the affected areas and with respect to the number of regenerated bile ducts. We suggest that following serious liver disorder, c-kit⁺CD34⁺cells are supplied early from the extrahepatic tissues for liver regeneration. These cells move to the regeneration site together with hepatic stem cells, and over time, play a role as hepatic tissue stem cells. It is probable that c-kit ⁺ CD34 ⁺ cells have the capacity to not only directly transdifferentiate into hepatocytes and biliary cells, but also to induce the growth and differentiation of hepatocytes.