Improvement of mortality rate and decrease in histologic hepatic injury after human cord blood stem cell infusion in a murine model of hepatotoxicity.
OBJECTIVE
Because of their plasticity potential local and systemic application of cord blood stem cells may represent excellent candidates for cell-based therapeutic strategies in toxic liver injuries. It is already known that intraperitoneal administration of hematopoietic stem cells provides rapid liver homing in animal models of hepatic injury. We sought to assess the efficacy of a hematopoietic stem cell infusion to decrease the histologic damage and the mortality rate of animals previously damaged by allyl alcohol.


METHODS
NOD/SCID mice were divided into two groups. (1) animals treated by intraperitoneal administration of allyl alcohol and (2) animals treated with allyl alcohol and 24 hours later with an intraperitoneal infusion of human cord blood cells. Flow cytometry, histology, immunohistochemistry, and RT-PCR were performed to monitor human cell engraftment by evidences of human hepatic markers.


RESULTS
Human stem cells were able to transdifferentiate into hepatocytes, improve liver regeneration after damage, and reduce the mortality rate even when requiring qualitative and quantitative differences in the transdifferentiation processes. The mortality rate decreased from 70% to 20%, with a significant improvement in the histologic findings.


CONCLUSIONS
We demonstrated that the infusion of hematopoietic stem cells into the liver in the early stage of damage might initiate endogenous hepatic tissue regeneration that oppose the injury inflicted by toxicants.
Di Campli
C
C
Department of Medical Pathology, Catholic University of Rome, Rome, Italy.
Piscaglia
A C
AC
Rutella
S
S
Bonanno
G
G
Vecchio
F M
FM
Zocco
M A
MA
Monego
G
G
Michetti
F
F
Mancuso
S
S
Pola
P
P
Leone
G
G
Gasbarrini
G
G
Gasbarrini
A
A
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D008107:Liver Diseases / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020005:Propanols / Q000633:toxicity; D014183:Transplantation, Heterologous / Q000473:pathology*
D020005:Propanols; C006463:allyl alcohol