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Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver.

ABSTRACT: Recent studies suggest that mesenchymal stem cells (MSCs) possess a greater differentiation potential than once thought and that they have the capacity to regenerate damaged tissues/organs. However, the evidence is insufficient, and the mechanism governing the recruitment and homing of MSCs to these injured sites is not well understood. We first examined the MSCs circulating in peripheral blood and then performed chemotaxis, wound healing and tubule-formation assays to investigate the migration capability of mouse bone marrow MSCs (mBM-MSCs) in response to liver-injury signals. In addition, BM-MSCs from donor enhanced green fluorescent protein transgenic male mice were transplanted into liver-injured co-isogenic female recipients, either by intra-bone marrow injection or through the caudal vein, to allow in vivo tracking analysis of the cell fate after transplantation. Donor-derived cells were analysed by in vivo imaging analysis, PCR, flow cytometry and frozen sections. Microarray and real-time PCR were used for chemokine/cytokine and receptor analyses. We successfully isolated circulating MSCs in peripheral blood of liver-injured mice and provided direct evidence that mBM-MSCs could be mobilized into the circulation and recruited into the liver after stimulation of liver injury. CCR9, CXCR4 and c-MET were essential for directing cellular migration towards the injured liver. The recruited mBM-MSCs may play different roles, including hepatic fate specification and down-regulation of the activity of hepatic stellate cells which inhibits over-accumulation of collagen and development of liver fibrosis. Our results provide new insights into liver repair involving endogenous BM-MSCs and add new information for consideration when developing clinical protocols involving the MSCs.

SUBMITTER: Chen Y

PROVIDER: S-EPMC3829016 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver.

Chen Ye Y Xiang Li-Xin LX Shao Jian-Zhong JZ Pan Ruo-Lang RL Wang Yu-Xi YX Dong Xue-Jun XJ Zhang Guo-Rong GR

Journal of cellular and molecular medicine 20090924 6B

Recent studies suggest that mesenchymal stem cells (MSCs) possess a greater differentiation potential than once thought and that they have the capacity to regenerate damaged tissues/organs. However, the evidence is insufficient, and the mechanism governing the recruitment and homing of MSCs to these injured sites is not well understood. We first examined the MSCs circulating in peripheral blood and then performed chemotaxis, wound healing and tubule-formation assays to investigate the migration ...[more]

PMID: 19780871

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Project description:AimRecent 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.MethodsMSCs 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.ResultsCompared 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.ConclusionMSCs 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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Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver.

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Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver.

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