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SDF-1/CXCR4 Axis Promotes MSCs to Repair Liver Injury Partially through Trans-Differentiation and Fusion with Hepatocytes.

Hao NB, Li CZ, Lü MH, Tang B, Wang SM, Wu YY, Liang GP, Yang SM - Stem Cells Int (2015)

Bottom Line: Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin.Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity.However, the percentage of transdifferentiation was significantly higher than fusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

ABSTRACT
MSCs have become a popular target for developing end-stage liver therapies. In this study, two models of bone marrow chimeric mice were used to construct the liver failure models. Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin. Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity. However, the percentage of transdifferentiation was significantly higher than fusion. So it was considered that MSCs which transdifferentiated into hepatocyte-likes cells played important roles for repairing the injuring liver function.

No MeSH data available.


Related in: MedlinePlus

The CXCL12-CXCR4 axis plays an important role in the chemotaxis of MSCs. (a-b) ELISA was used to detect SDF-1 and CXCR4 protein levels in the damaged liver tissue at different times after injury. The data are the mean ± SEM from three independent experiments (*P < 0.05 compared with day 0). (c-d) 1 × 106 MSCs were preincubated with 17-AAG (SDF-1 inhibitor, 20 ng/mL) or PBS for 30 min and injected into the tail veins of bone marrow-destroyed female C57BL/6 mice. Then, liver damage was induced in the mice, and tissue sections were collected 21 days after injury. (c) IF was used to detect ALB-positive cells, and FISH was used to identify the Y chromosome-positive cells. Bar: 75 μm. Arrow was directed to the double positive cells. (d) Both ALB- and FISH-positive cells were counted. All the experiments were repeated three times, at least 3 samples were included in each group.
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fig4: The CXCL12-CXCR4 axis plays an important role in the chemotaxis of MSCs. (a-b) ELISA was used to detect SDF-1 and CXCR4 protein levels in the damaged liver tissue at different times after injury. The data are the mean ± SEM from three independent experiments (*P < 0.05 compared with day 0). (c-d) 1 × 106 MSCs were preincubated with 17-AAG (SDF-1 inhibitor, 20 ng/mL) or PBS for 30 min and injected into the tail veins of bone marrow-destroyed female C57BL/6 mice. Then, liver damage was induced in the mice, and tissue sections were collected 21 days after injury. (c) IF was used to detect ALB-positive cells, and FISH was used to identify the Y chromosome-positive cells. Bar: 75 μm. Arrow was directed to the double positive cells. (d) Both ALB- and FISH-positive cells were counted. All the experiments were repeated three times, at least 3 samples were included in each group.

Mentions: Recent studies have reported that the chemokine SDF-1 and its receptor CXCR4 play a pivotal role in the migration, chemotaxis, homing, and transdifferentiation of MSCs [20]. Therefore, we determined the concentration of SDF-1 and CXCR4 on days 0, 2, 3, 4, 7, 14, 21, and 28 by ELLISA. As shown in Figure 4(a), the concentration of SDF-1 gradually increased and reached its peak on day 21. Consistent with SDF-1, the expression of CXCR4 was also significantly elevated on day 21 (Figure 4(b)).


SDF-1/CXCR4 Axis Promotes MSCs to Repair Liver Injury Partially through Trans-Differentiation and Fusion with Hepatocytes.

Hao NB, Li CZ, Lü MH, Tang B, Wang SM, Wu YY, Liang GP, Yang SM - Stem Cells Int (2015)

The CXCL12-CXCR4 axis plays an important role in the chemotaxis of MSCs. (a-b) ELISA was used to detect SDF-1 and CXCR4 protein levels in the damaged liver tissue at different times after injury. The data are the mean ± SEM from three independent experiments (*P < 0.05 compared with day 0). (c-d) 1 × 106 MSCs were preincubated with 17-AAG (SDF-1 inhibitor, 20 ng/mL) or PBS for 30 min and injected into the tail veins of bone marrow-destroyed female C57BL/6 mice. Then, liver damage was induced in the mice, and tissue sections were collected 21 days after injury. (c) IF was used to detect ALB-positive cells, and FISH was used to identify the Y chromosome-positive cells. Bar: 75 μm. Arrow was directed to the double positive cells. (d) Both ALB- and FISH-positive cells were counted. All the experiments were repeated three times, at least 3 samples were included in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: The CXCL12-CXCR4 axis plays an important role in the chemotaxis of MSCs. (a-b) ELISA was used to detect SDF-1 and CXCR4 protein levels in the damaged liver tissue at different times after injury. The data are the mean ± SEM from three independent experiments (*P < 0.05 compared with day 0). (c-d) 1 × 106 MSCs were preincubated with 17-AAG (SDF-1 inhibitor, 20 ng/mL) or PBS for 30 min and injected into the tail veins of bone marrow-destroyed female C57BL/6 mice. Then, liver damage was induced in the mice, and tissue sections were collected 21 days after injury. (c) IF was used to detect ALB-positive cells, and FISH was used to identify the Y chromosome-positive cells. Bar: 75 μm. Arrow was directed to the double positive cells. (d) Both ALB- and FISH-positive cells were counted. All the experiments were repeated three times, at least 3 samples were included in each group.
Mentions: Recent studies have reported that the chemokine SDF-1 and its receptor CXCR4 play a pivotal role in the migration, chemotaxis, homing, and transdifferentiation of MSCs [20]. Therefore, we determined the concentration of SDF-1 and CXCR4 on days 0, 2, 3, 4, 7, 14, 21, and 28 by ELLISA. As shown in Figure 4(a), the concentration of SDF-1 gradually increased and reached its peak on day 21. Consistent with SDF-1, the expression of CXCR4 was also significantly elevated on day 21 (Figure 4(b)).

Bottom Line: Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin.Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity.However, the percentage of transdifferentiation was significantly higher than fusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

ABSTRACT
MSCs have become a popular target for developing end-stage liver therapies. In this study, two models of bone marrow chimeric mice were used to construct the liver failure models. Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin. Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity. However, the percentage of transdifferentiation was significantly higher than fusion. So it was considered that MSCs which transdifferentiated into hepatocyte-likes cells played important roles for repairing the injuring liver function.

No MeSH data available.


Related in: MedlinePlus