Fig. 5

Oval cells regenerate large-scale hepatocytes in a noncompetitive environment. a DPPIV-chimeric lineage tracing system subjected to AAF/PH treatment followed by two doses of retrorsine 2 weeks apart at 1 and 3 weeks after cessation of AAF (AAF/PH/retrorsine). b A whole liver section of a DPPIV-chimeric liver at 1 week after AAF/PH/retrorsine treatment was stained for DPPIV and GGT. Oval cell proliferation infiltrated less extensively into the hepatic lobules. GGT(+)/DDPIV(−) foci of variable sizes were easily observed. These GGT(+)/DPPIV(−) foci were comprised of differentiating oval cells and newly formed hepatocytes [OV6(+)/C/EBPα(+), HNF4α(+)/EpCAM(+)] . c DPPIV-deficient rats received DPPIV(+) oval cells transplantation (OCT) combined with AAF/PH/retrorsine injury. After 4 weeks following AAF/PH/retrorsine injury, DPPIV(+) oval cells regenerated large-scale DPPIV(+) hepatocyte clusters. At higher magnification, DPPIV(+) oval cell–derived hepatocytes were histologically identical to the surrounding DPPIV(−) hepatocytes. Both DPPIV(+)/GGT(+) (circles) and DPPIV(−)/GGT(+) (arrow) clusters, indicating transplanted and host oval cell–derived hepatocytes respectively, were seen. Original magnification: b 100×/zoom magnification 200×; c 100×/zoom magnification 200×. Scale bars: b 300 μm; b b’1–b’4 100 μm; c 300 μm