Fig. 4

Histological changes in graft vessels 90 days after transplantation. a Transplant arteriosclerosis characterized by intimal hyperplasia was observed in all groups except the isograft. Hyperplastic neointima was composed of abundant spindle-shaped cells and extracellular matrix mixed with some degree of inflammation internal to the elastic membrane. Intravenous injection of pLV-HMGB1-transfected MSCs reduced neointimal thickness to the least degree in all allograft groups. However, no favorable effect was elicited by transfection of MSCs with pshRNA-RAGE1 or pshRNA-RAGE3. The neointimal thickness was normalized to the full thickness of vessel walls and expressed as a percentage. Eight rats were examined for each group to calculate the average neointimal thickness. b Macrophage infiltration in graft vessels was detected by immunohistochemistry for CD68. Quantitative analysis of CD68⁺ cells in the neointima (marked with yellow arrows) revealed that MSC infusion reduced the fraction of CD68⁺ cells in total neointimal cells. Transfection of pLV-HMGB1 dramatically improved these effects, which were not produced by transfection of either pshRNA-RAGE1 or pshRNA-RAGE3. Five random high-power fields were examined in the sections of graft vessels for each rat, and the neointimal cell number was counted to determine the percentage of CD68⁺ cells in the total cell population. The average percentage was calculated from eight rats for each group. Group comparisons were made using the Mann-Whitney test. **P < 0.05. H&E hematoxylin and eosin, HMGB1 high mobility group box 1, RAGE receptor for advanced glycation end-product