Characterisation of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver

Abstract

Background-Stem/progenitor cell niches in tissues regulate stem/progenitor cell differentiation and proliferation through local signalling.

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

“…during injury (18). Ductular proliferation and liver growth then occurs, principally following the loss of engrafted cells but with the additional accumulation of endogenous macrophages, again mirroring observations in an injury model (22).…”

“…During liver injury, macrophages are recruited from the bone marrow (BM) to engraft within the liver adjacent to DRs (18). Regeneration of any organ in response to injury is accompanied by macrophage infiltration, which is believed primarily to clear cellular debris.…”

Liver precursor cells increase hepatic fibrosis induced by chronic carbon tetrachloride intoxication in rats

“…The fact that TGFb was also detected in LPC from rats treated with AAF alone in the absence of aSMA-positive cells close to LPC, points out that LPC and TGFb alone are not sufficient to induce activation of HSC or of portal fibroblasts. In the group AAF, we observed an enhanced hepatic expression of collagen 4 and an accumulation of laminin (data not shown), two components of the basement membrane secreted by quiescent HSC in contact with LPC, 3,20 which may account for the faint picrosirius red labeling around portal areas. In summary, these data suggest that LPC alone are not fibrogenic when there is no hepatocellular damage, and they emphasize the need of CCl 4 -induced injury to promote HSC activation and subsequent fibrosis.…”

“…2,11,14,15,47,48 Activated HSC 18,49 and portal fibroblasts 45 are a major source of growth factors for LPC and recent data established that myofibroblasts are required for LPC response 11,19 and are a component of the LPC niche. 20 Conversely, it has not been clearly shown whether LPC could cause HSC or portal fibroblast activation. The aSMA staining, the most widely used technique that reveals myofibroblasts, could not distinguish in our study between both types of cells.…”

“…19 Therefore, HSC or portal fibroblast activation seems a prerequisite for LPC expansion, as already demonstrated in other stem cell niches. 20 Additionally, myofibroblast-LPC cross-talk could indirectly enhance fibrogenesis by recruiting cells of innate immune response, such as leukocytes required for wound healing. 21 Among the large variety of factors secreted by myofibroblasts, transforming growth factor-b (TGFb), the most potent fibrogenic cytokine, is also a well-established mediator of epithelial-mesenchymal transition (EMT), which contributes to fibrosis following injury in several organs including the liver.…”