Abstract

6bone marrow-derived MSCs were administered, either intravenously (i.v.) through the tail vene or locally in the capsule of one of the 2 remaining fibrotic liver lobes. After 8 days the mice were sacrificed and the completely regenerated livers removed. Results: Histochemical analyses, by routine histology and Sirius red staining of the collagen deposition, revealed that in the liver lobes of control animals (n = 7) no fibrotic septa or lobuli were present. In the hepatectomized liver parts (n = 89) of the CCL4-treated animals the fibrotic septa/lobuli formation was 66±3%. In the CCL4-treated control group (n = 13) fibrotic septa/lobuli in both regenerated lobes was 15±4% and 18±5%. Intravenous administration of MSCs (n = 8) had resulted in a significantly (P < 0.05) increased fibrotic septa/ lobuli formation, i.e., 28±6% and 33±6% of the regenerated lobes. Remarkably, local administration of MSCs in the capsule (n = 7) resulted in a significantly (P < 0.05) decreased fibrosis of the septa/ lobuli to 8±2% of that liver lobe. In the counterpart liver lobe, which received no local MSCs, the fibrosis formation was 22±8%, comparable to the CCL4 controls and somewhat lower (ns) than in the MSCs-i.v. group. Conclusions: Local administration of MSCs to liver lobes resulted in an almost normal regenerated liver, but not in the in situ liver counterpart, whereas intravenous administration of MSCs significantly increased fibrosis in the regenerated livers. These observations indicate that the route of MSC administration determines the effect on the fibrotic process in the liver.

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