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


CONCLUSIONS
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.
Lu
Hai-hua
HH
Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Teng
Gao-jun
GJ
Ju
Sheng-hong
SH
Sun
Jun-hui
JH
Li
Ai-mei
AM
Zhang
Ai-feng
AF
D000818:Animals; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008107:Liver Diseases / Q000503:physiopathology / Q000601:surgery*; D008111:Liver Function Tests; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011897:Random Allocation
D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride