Hematopoietic stem cell mobilization after rat partial orthotopic liver transplantation.

BACKGROUND

On the basis of the recently recognized potential of hematopoietic stem cells (HSC) to give rise to hepatocytes, we investigated the possibility that HSC could be mobilized and home to the injured liver promoting tissue repair after 50% partial orthotopic liver transplantation (PLTx) in the rat.

METHODS

Using sex-mismatched (female to male) syngeneic SD rats, we performed 50% PLTx or whole orthotopic liver transplantation (WLTx) versus 50% partial hepatectomy (PHx) and sham operation (O). Elements with stem cell markers were detected in peripheral blood (PB) and in the liver. Liver injury and regeneration were estimated. The sex-determining region for Y chromosome gene (SRY) was used to define cell origin by in situ hybridization in liver sections.

RESULTS

Comparison of WLTx and PHx groups showed a lower survival rate (50%), in the PLTx group were (P<.05). Further, the liver injury was more serious and the levels of serum biochemical parameters were higher. Compared with PHx groups, on days 3 and 5 postoperatively, the mitosis index and the expression of PCNA were lower among the PLTx groups. Compared with WLTx and sham operation groups, beta2m-/Thy-1.1+, CD34+ cells in PB in PLTx groups and PHx were increased on day 1 postoperatively and decreased on the following days. Compared with PHx groups, beta2m-/Thy-1.1+, CD34+ cells were higher in PLTx. The CD34-, c-kit-, and Thy-1.1-positive cells detected in portal tract areas peaked during 3 to 5 days postoperatively in PLTx. Few SRY+ cells were detected in PLTx liver grafts.

CONCLUSIONS

beta2m-/Thy-1.1+ and CD34+ stem cells mobilized after PLTx and PHx may be related to the reduced-size liver. Few HSC are involved in liver regeneration in PLTx.