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Molecular Imaging and Biology

, Volume 18, Issue 1, pp 43–51 | Cite as

Transplantation of MSCs Overexpressing HGF into a Rat Model of Liver Fibrosis

  • Lisha Lai
  • Junwei Chen
  • Xinhua Wei
  • Mingsheng Huang
  • Xiaojun Hu
  • Ruimeng Yang
  • Xinqing Jiang
  • Hong Shan
Research Article

Abstract

Purpose

The aim of this study is to evaluate the effect of overexpressing human hepatocyte growth factor (HGF) for mesenchymal stem cells (MSCs) in liver fibrosis regeneration and magnetic resonance (MR) tracking of MSCs in rat liver.

Procedures

MSCs were transfected with ad-HGF/ad-green fluorescent protein (GFP) and labeled with superparamagnetic iron oxide (SPIO). The characteristics of SPIO-HGF/MSCs were investigated. Prussian blue staining for iron assessment was conducted in vitro and in vivo. SPIO-HGF/MSCs (group A) or SPIO-GFP/MSCs (group B) were transplanted into a rat model of liver fibrosis, and MR imaging of the rat liver was performed. The signal to noise ratio (SNR) and R2* (1/T2*) value were measured. Prussian blue staining was performed to detect the in vivo distribution of MSCs, and liver Ki67 immunohistochemistry (IHC) staining was studied. The serum levels of HGF, alanine aminotransferase (ALT) and hyaluronic acid (HA) were determined.

Results

The positive rate of HGF transfection was 93.17 % and the HGF/MSCs were labeled with SPIO successfully (97.80 ± 1.06 %). Labeling of MSCs with SPIO did not alter cell proliferation in vitro. The signal intensity of liver T2* WI images decreased on day 1 after cell transplantation and recovered to pre-transplantation level on day 15 (group A) and day 13 (group B). The SNR of group A were significantly lower than that of group B (P = 0.006), and the R2* values of group A were significantly higher than those of group B (P < 0.001). The R2* value had a significantly negative correlation with SNR. There were more Prussian blue-positive cells in of group A were more than in group B in vivo. The positive rate of Ki67 was 16.11 ± 2.13 %, and the serum level of ALT/HA was decreased in group A.

Conclusion

HGF transfection improved MSCs localization in the liver and aided liver repair. The R2* value might be a feasible index in addition to SNR to track the SPIO-MSC transplantation in the liver.

Key words

Mesenchymal stem cells Hepatocyte growth factor Superparamagnetic iron oxide Magnetic resonance imaging Liver fibrosis 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (nos. U1032002, 81172193, and 81070349).

Conflict of Interest

The authors have declared that they have no conflict of interest.

Supplementary material

11307_2015_869_MOESM1_ESM.pdf (397 kb)
ESM 1 (PDF 397 kb)

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Copyright information

© World Molecular Imaging Society 2015

Authors and Affiliations

  • Lisha Lai
    • 1
    • 2
  • Junwei Chen
    • 2
  • Xinhua Wei
    • 1
  • Mingsheng Huang
    • 2
    • 3
  • Xiaojun Hu
    • 2
  • Ruimeng Yang
    • 1
  • Xinqing Jiang
    • 1
  • Hong Shan
    • 2
    • 3
  1. 1.Department of Radiology, Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhouChina
  2. 2.Department of RadiologyThe Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  3. 3.Interventional Radiology InstituteSun Yat-Sen UniversityGuangzhouChina

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