Z Gastroenterol 2009; 47 - P3_29
DOI: 10.1055/s-0029-1191886

Increased susceptibility to apoptosis as a result of aging leads to a dramatic increase in liver repopulation by transplanted fetal liver stem/progenitor cells

A Menthena 1, CI Koehler 1, JS Sandhu 1, DA Shafritz 1, M Oertel 1
  • 1Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, USA

Recently, we showed that normal adult rat liver can be replaced by transplanting fetal liver stem/progenitor cells (FLSPC). Liver repopulation occurs by cell competition between transplanted FLSPC and host hepatocytes during which the former replace the latter by inducing their apoptosis. In the present study, we compared the repopulation potential of FLSPC after their transplantation into rats of different ages (2, 6, 14 mo.).

Embryonic day 14 (ED14) fetal liver cells from DPPIV+ F344 rats were transplanted into mutant DPPIV– F344 rats and 6 mo. later, we observed 4.5% liver replacement by transplanted FLSPC in 2 mo. old rats, but repopulation levels increased to 11.5% in 6 mo. old rats (P=0.002) and 22.6% in 14 mo. old rats (P<0.001).

The mechanism for increased hepatic replacement by transplanted FLSPC in older animals was determined by measuring rates of proliferation and apoptosis in the liver of rats at different ages. There was decreased proliferative activity and apoptotic rate in hepatocytes of 6 or 14 mo. vs. 2 mo. old rats. We then measured proliferation and apoptotic rates of cells in transplanted DPPIV+ clusters vs. surrounding DPPIV– host liver in young rats (2 mo.) vs. older rats (14 mo.). The proliferative index of transplanted cells was 3–5 fold higher than in host hepatocytes in both young and older rats; however, apoptosis of host hepatocytes after transplanting FLSPC increased dramatically in older rats compared to younger rats (0.7% vs. 0.23%, P<0.001).

The level of long-term tissue reconstitution obtained in older rats after transplantation of FLSPC far exceeds that observed in younger rats in a normal hepatic environment, and this increased repopulation by FLSPC appears to result from increased susceptibility of host hepatocytes to apoptosis as a result of aging. Therefore, the potential use of cell transplantation in such individuals has significant clinical implications for the treatment of chronic liver diseases in the elderly.