Syngenic Bone Marrow Cells Restore Hepatic Function in Carbon Tetrachloride-Induced Mouse Liver Injury

Abstract

Progenitor cells in bone marrow have been explored for the treatment of liver injury. Stem cell homing to the injured tissue is regulated through stromal cell derived factor-1 (SDF-1) and its receptor CXCR4. We hypothesized that syngenic bone marrow cells (BMCs) would restore hepatic function in the injured liver through the regulation by SDF-1/CXCR4 system. After injecting carbon tetrachloride (CCl(4)), the mice were injected with syngenic BMCs or normal saline. Morphological and functional analysis of the liver was performed. Flow cytometry for the stem cell markers and CXCR4 was done with the liver, BM, and spleen cells from each group. Carboxyfluorescein diacetate succinimidyl ester was used to trace the homing of transplanted BMCs. The SDF-1 expression of the liver was assessed by immunohistochemistry. Hepatosplenomegaly and necrosis of the CCl(4)-injected mouse liver were improved after BMCs transplantation The hepatic enzymes were increased after injury and then decreased after BMCs transplantation. The expression of stem cell markers and CXCR4 was exclusively increased in the damaged liver compared to the BM and spleen, and even more elevated after BMCs transplantation. SDF-1 expression in the liver was observed after CCl(4) injection and it was elevated after BMCs transplantation. The intrinsic and extrinsic BMCs migrate specifically to the injured liver rather than BM or spleen, and the transplanted BMCs contribute to the repair of the damaged liver. SDF-1/CXCR-4 interaction plays a role in stem cell homing toward the damaged organ, and transplanted BMCs are involved in the up-regulated SDF-1 expression seen in the injured liver.