[Committed differentiation of transplanted bone derived mesenchymal stem cells and their potential to amend damaged liver functions: in vivo experiment with mice]

Zhonghua Yi Xue Za Zhi. 2007 Jan 23;87(4):223-7.
[Article in Chinese]

Abstract

Objective: To observe whether bone mesenchymal stem cells (MSCs) have the potential to transdifferentiate into functional hepatocyte-like cells in the special "niche" as well as the therapeutic feasibility to repair damaged liver in mice.

Methods: 20 nude mice were randomly divided into four groups (n = 5 in each group): Group A: 1.0 ml/kg of carbon tetrachloride (CCl(4)) (dissolved in olive oil by ratio of 1:1) was injected into the peritoneum of mice twice a week for 5 weeks. GFP-positive MSCs (1 x 10(6) cells) were injected into the caudal tail vein 1 week after the first dose of CCl(4); Group B: treated with CCl(4) as in A, but received the same volume of saline; Group C: normal nude mice with GFP-positive MSCs Transplanted in the same way as in A. Group D: normal controls. 4 weeks after the cell transplantation, all animal subjects were killed. Liver function tests (LFT), histology of HE and Masson staining as well as double immunofluorescent staining for GFP and albumin were studied in all groups.

Results: The hepatic fibrosis in group A & B confirmed the success of model for liver damage and there was no marked difference in the percent of the area occupied by collagen between two groups (10.5 +/- 1.5 vs 12.7 +/- 1.6, t = -2.238, P > 0.05). GFP-positive MSCs were mainly observed around portal area or interspace of lobules in group A. Some of GFP-positive cells also express albumin (35% +/- 7%). While in group B, C or D, there is no such findings. The level of serum albumin in group A was higher than that in group B (24.4 g/L +/- 3.3 g/L vs 18.6 g/L +/- 2.9 g/L, P < 0.05) while the level of ALT was also different between two groups (121 U/L +/- 21 U/L vs 192 U/L +/- 29 U/L, P < 0.05).

Conclusion: The stimulus of persistent liver damage might enhances the migration of MSCs to the liver, in which some of the MSCs have the potential to transdifferentiate into hepatocyte-like cells. Transplantation of MSCs might amend the damaged tissue of host liver to a certain extent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride
  • Cell Differentiation*
  • Cell Transdifferentiation
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Liver Diseases / physiopathology
  • Liver Diseases / surgery*
  • Liver Function Tests
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Random Allocation

Substances

  • Green Fluorescent Proteins
  • Carbon Tetrachloride