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Destruction of bile ducts by 4,4′‐diaminodiphenylmethane does not block the small hepatocyte‐like progenitor cell response in retrorsine‐exposed rats
Author(s) -
Best D. Hunter,
Coleman William B.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a70-d
Subject(s) - progenitor cell , hepatocyte , liver regeneration , liver injury , population , liver cell , chemistry , progenitor , regeneration (biology) , cell , andrology , stem cell , endocrinology , pathology , biology , medicine , microbiology and biotechnology , biochemistry , in vitro , environmental health
Liver regeneration after partial hepatectomy (PH) in rats exposed to the mito‐inhibitory agent retrorsine is accomplished through proliferation/differentiation of small hepatocyte‐like progenitor cells (SHPC). The origin of SHPC is unknown. We have investigated the possibility that SHPC are derived from oval cells (OC), a known liver progenitor cell that resides in the bile ducts of the liver, by combining the retrorsine/PH (RP) liver injury/regeneration model with 4,4′‐diaminodiphenylmethane (DAPM), a toxin that results in the targeted destruction of bile ducts in rodent liver. F344 rats were treated with retrorsine (30 mg/kg i.p. each) at 6 and 8 weeks of age followed by PH 5 weeks later. 24 hours prior to PH, animals received a single dose of DAPM (50 mg/kg i.p.). Livers from DAPM/RP animals exhibit a regenerative response similar to RP animals. SHPC clusters emerge at 3d post‐PH and continue to expand through 21d post‐PH with normalization of the liver by 30d post‐PH. OC are never observed in DAPM treated rats and SHPCs are never observed in rats in the absence of retrorsine treatment. These results suggest strongly that OC are not the cell of origin of the SHPC, and that SHPC represent a distinct population of progenitor cells capable of responding to liver injury/deficit to restore normal liver mass and structure. Support: NIH CA78343 and T32 ES 017017.