Human platelets promote liver regeneration with Kupffer cells in SCID mice.

BACKGROUND

Platelets contain several growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor. We examined the role of human platelets in liver regeneration with a focus on Kupffer cells (KCs).

MATERIALS AND METHODS

Severe combined immunodeficiency mice were subjected to 70% hepatectomy and phosphate-buffered saline administration (PBS); 70% hepatectomy and human platelet transfusion (hPLT); 70% hepatectomy, KC depletion, and PBS administration (KD + PBS); 70% hepatectomy, KC depletion, and human platelet transfusion (KD + hPLT); or a sham operation and human platelet transfusion (sham). The groups were evaluated for liver regeneration, accumulation and activation of human platelets in the liver, and/or co-localization of platelets and KCs.

RESULTS

The liver-to-body weight ratio was significantly higher 48 h post-transfusion in the hPLT group compared with the PBS, KD + PBS, and KD + hPLT groups. Human VEGF concentrations were higher in liver tissues from the hPLT group, whereas VEGF was not detected in the other groups. Hepatic levels of KC-derived cytokines were elevated in the hPLT group compared with the PBS group. Molecules in signaling cascades downstream of these cytokines were phosphorylated earlier and more robustly in the hPLT group than in the PBS group. Activated human platelets accumulated in livers in the hPLT group, whereas fewer platelets accumulated and many were not activated in the sham and KD + hPLT groups. In the hPLT group, most human platelets were attached to KCs.

CONCLUSIONS

Human platelet transfusion promoted liver regeneration in severe combined immunodeficiency mice. Together, human platelets and KCs resulted in growth factor release and enhanced liver regeneration.