A human umbilical cord stem cell rescue therapy in a murine model of toxic liver injury.
BACKGROUND
Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver.


OBJECTIVE
In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice.


METHODS
We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment.


RESULTS
Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process.


CONCLUSIONS
We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.
Department of Internal Medicine, Catholic University of Rome, Rome, Italy.
C
C
Di Campli
A C
AC
Piscaglia
L
L
Pierelli
S
S
Rutella
G
G
Bonanno
M R
MR
Alison
A
A
Mariotti
F M
FM
Vecchio
M
M
Nestola
G
G
Monego
F
F
Michetti
S
S
Mancuso
P
P
Pola
G
G
Leone
G
G
Gasbarrini
A
A
Gasbarrini
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7; D007633:Keratins / Q000032:analysis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020005:Propanols / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
C507497:KRT7 protein, human; D053552:Keratin-7; C507496:Krt7 protein, mouse; D020005:Propanols; D012333:RNA, Messenger; C006463:allyl alcohol; D007633:Keratins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases