Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function
Takanori Kuroiwa, … , Jiro Fujimoto, Tsuyoshi Iwasaki
Takanori Kuroiwa, … , Jiro Fujimoto, Tsuyoshi Iwasaki
Published June 1, 2001
Citation Information: J Clin Invest. 2001;107(11):1365-1373. https://doi.org/10.1172/JCI11808.
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Article

Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function

Abstract

Acute graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation (BMT) and is characterized by hematopoietic dysfunction, immunosuppression, and tissue injury in the skin, liver, and intestinal mucosa. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, induces mitogenic and antiapoptotic activity in various epithelial cells and promotes hematopoiesis. Working in a murine model of acute GVHD, we performed repeated transfection of the human HGF cDNA into skeletal muscle and showed that this treatment inhibited apoptosis of intestinal epithelial cells and donor T-cell infiltration into the liver, thereby ameliorating the enteropathy and liver injury caused by acute GVHD. HGF also markedly suppressed IFN-γ and TNF-α expression in the intestine and liver and decreased the serum IL-12. Furthermore, extramedullary hematopoiesis by donor cells was increased, and the survival rate was improved. These results suggest that HGF may be useful for controlling acute GVHD after allogeneic BMT.

Authors

Takanori Kuroiwa, Eizo Kakishita, Teruaki Hamano, Yasuro Kataoka, Yoshifumi Seto, Nobuo Iwata, Yasufumi Kaneda, Kunio Matsumoto, Toshikazu Nakamura, Takahiro Ueki, Jiro Fujimoto, Tsuyoshi Iwasaki

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Augmentation of hematopoietic function by HGF in a syngeneic BMT model. ...
Augmentation of hematopoietic function by HGF in a syngeneic BMT model. Recipients were transplanted with 5 × 106 bone marrow cells from syngeneic (BDF1) donors after 9 Gy of TBI. HGF-HVJ liposomes (or PBS) were injected on days 0 and 7. Ten days after BMT, histological examination was performed (a), and the peripheral blood cell profile, as well as the number of spleen cells, bone marrow cells, and thymus cells (b), was determined. (a) Hematoxylin and eosin staining of the liver and spleen in syngeneic BMT mice with or without HGF gene transduction. Liver tissue from HGF-treated GVHD mice showed hematopoietic foci containing granulocyte precursor cells and erythroblasts (arrow). Spleen tissue from HGF-treated GVHD mice showed marked extramedullary hematopoiesis along with numerous megakaryocytes (arrow). ×200. (b) The peripheral blood cell profile and the number of spleen cells, bone marrow cells, and thymus cells are shown as the mean ± SD of four mice. AP < 0.05.