Fig. 3.23 http://ebooksmedicine.net • Tissue regeneration can occur in parenchymal organs whose cells are capable of proliferation, but with the exception of the liver, this is usually a limited process. Pancreas, adrenal, thyroid, and lung have some regenerative capacity. The surgical removal of a kidney elicits in the remaining kidney a compensatory response that consists of both hypertrophy and hyperplasia of proximal duct cells. The mechanisms underlying this response are not understood, but they likely involve local production of growth factors and interactions of cells with the ECM. The extraordinary capacity of the liver to regenerate has made it a valuable model for studying this process, as described below.
Restoration of normal tissue architecture can occur only if the residual tissue is structurally intact, for example after partial surgical resection of the liver. By contrast, if the entire tissue is damaged by infection or inflammation, regeneration is incomplete and is accompanied by scarring. For example, extensive destruction of the liver with collapse of the reticulin framework, as occurs in a liver abscess, leads to scar formation even though the remaining liver cells have the capacity to regenerate.
The human liver has a remarkable capacity to regenerate, as demonstrated by its growth after partial hepatectomy, which may be performed for tumor resection or for living-donor hepatic transplantation. The mythologic image of liver regeneration is the regrowth of the liver of Prometheus, which was eaten every day by an eagle sent by Zeus as punishment for stealing the secret of fire, and regrew every night. The reality, although less dramatic, is still quite impressive.
Regeneration of the liver occurs by two major mechanisms: proliferation of remaining hepatocytes and repopulation from progenitor cells. Which mechanism plays the dominant role depends on the nature of the injury.
Proliferation of hepatocytes following partial hepatectomy. In humans, resection of up to 90% of the liver can be corrected by proliferation of the residual hepatocytes. This process is driven by cytokines such as IL-6 produced by Kupffer cells, and by growth factors such as hepatocyte growth factor (HGF) produced by many cell types.
Liver regeneration from progenitor cells. In situations in which the proliferative capacity of hepatocytes is impaired, such as after chronic liver injury or inflammation, progenitor cells in the liver contribute to repopulation. In rodents, these progenitor cells have been called oval cells because of the shape of their nuclei. Some of these progenitor cells reside in specialized niches called canals of Hering, where bile canaliculi connect with larger bile ducts. The signals that drive proliferation of progenitor cells and their differentiation into mature hepatocytes are topics of active investigation.
Different tissues consist of continuously dividing cells (epithelia, hematopoietic tissues), normally quiescent cells that are capable of proliferation (most parenchymal organs), and non-dividing cells (neurons, skeletal and cardiac muscle).The regenerative capacity of a tissue depends on the proliferative potential of its constituent cells.
Cell proliferation is controlled by the cell cycle, and is stimulated by growth factors and interactions of cells with the extracellular matrix.
Regeneration of the liver is a classic example of repair by regeneration. It is triggered by cytokines and growth factors produced in response to loss of liver mass and inflammation. In different situations, regeneration may occur by proliferation of surviving hepatocytes or repopulation from progenitor cells.