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Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats.

ABSTRACT: Rapid regeneration of the remnant liver is critical for preventing liver failure and promoting recovery after extensive liver resection. Numerous studies have demonstrated the involvement of bone marrow-derived stem cells in liver regeneration and the potential benefits of bone marrow stem cell therapy. To avoid the preparation of stem cells, we proposed in this study to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (A), an antagonist of CXCR4 and low-dose FK506 (F). Here we show that AF combination therapy significantly increased lineage negative (Lin-) CD34+?and Lin-CD133+?stem cells in peripheral blood and enhanced recruitment of CD133+?cells into the remnant liver in a rat model of 85% partial hepatectomy. Recruiting CD133+?stem cells in the remnant liver was associated with increased proliferation of hepatic oval cells and paralleled the increased SDF-1, CXCR4 and HGF expression. Importantly, AF combination therapy increased the number of Ki67 positive hepatocytes and BrdU incorporation in the remnant liver and improved serum levels of albumin. Our results demonstrate that pharmacological mobilization of endogenous bone marrow stem cells with AF combination therapy can enhance endogenous stem cell mobilization to promote liver regeneration and improve liver function after extensive hepatectomy.

SUBMITTER: Zhai R

PROVIDER: S-EPMC5827664 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats.

Zhai Rujun R Wang Yongchun Y Qi Le L Williams George Melville GM Gao Bin B Song Guang G Burdick James F JF Sun Zhaoli Z

Scientific reports 20180226 1

Rapid regeneration of the remnant liver is critical for preventing liver failure and promoting recovery after extensive liver resection. Numerous studies have demonstrated the involvement of bone marrow-derived stem cells in liver regeneration and the potential benefits of bone marrow stem cell therapy. To avoid the preparation of stem cells, we proposed in this study to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (A), an antagonist of CXCR4 and low ...[more]

PMID: 29483616

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Project description:AIM:Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing inflammation, collagen deposition, and remodeling. These results provide a clue to treatment of liver fibrosis. The aim of this study was to investigate the effect of infusion of bone marrow (BM)-derived MSCs on the experimental liver fibrosis in rats. METHODS:MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats induced with carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN). There were two random groups on the 42nd d of CCl4:CCl4/MSCs, to infuse a dose of MSCs alone; CCl4/saline, to infuse the same volume of saline as control. There were another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10; DMN20/MSCs, to infuse the same dose of MSCs on d 20. The morphological and behavioral changes of rats were monitored everyday. After 4-6 wk of MSCs administration, all rats were killed and fibrosis index were assessed by histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of liver were tested by immunohistochemistry and quantified by IBAS 2.5 software. Male rats sex determination region on the Y chromosome (sry) gene were explored by PCR. RESULTS:Compared to controls, infusion of MSCs reduced the mortality rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model (20-40% vs 90%). The amount of collagen deposition and alpha-SMA staining was about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The similar results were observed in fibrosis index. And the effect of the inhibition of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was positive in the liver of rats with MSCs treatment by PCR. CONCLUSION:MSCs treatment can protect against experimental liver fibrosis in CCl4-induced or DMN-induced rats and the mechanisms of the anti-fibrosis by MSCs will be studied further.

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Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats.

Publications

Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats.

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