How does human stem cell therapy influence gene expression after liver injury? Microarray evaluation on a rat model.
BACKGROUND
Tissue homeostasis is guaranteed by stem proliferating reserve, depending on dynamic changes in gene expression. A high plasticity is shown by the haematopoietic stem cells, potential source for liver regeneration.


OBJECTIVE
We aimed to evaluate the gene expression modifications induced by human haematopoietic stem cell therapy after liver injury in rats.


METHODS
Rats were sorted as follows: (A) human-haematopoietic stem cell injection after allyl alcohol liver damage; (B) only haematopoietic stem cell injection; (C) only allyl alcohol injection; and (D) sacrifice without any treatment.


METHODS
Livers, spleens and bone marrows were analysed with flow-cytometry. Livers were also studied by reverse-transcription PCR, histology, immunohistochemistry and microarray analysis; selected genes were confirmed by real-time PCR.


RESULTS
In subset A, haematopoietic stem cells were selectively recruited by liver, with respect to the group B, and they improved the liver regeneration process compared to group C. As regards microarrays, haematopoietic stem cell infusion upregulates 265 genes and downregulates 149 genes. Differentially regulated genes belong to a broad range of functional pathways, including proliferation, differentiation, adhesion/migration and transcripts related to oval-cell activation. Real-time PCR validated array results.


CONCLUSIONS
Our study confirmed the capacity of haematopoietic stem cells to contribute to liver regeneration. Moreover, microarray analysis led to the identification of genes whose regulation strongly correlates with a more efficient process of liver repair after haematopoietic stem cell injection.
Piscaglia
A C
AC
Department of Internal Medicine and Gastroenterology, Catholic University of Rome, Italy.
Zocco
M A
MA
Di Campli
C
C
Sparano
L
L
Rutella
S
S
Monego
G
G
Bonanno
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 / Q000209:etiology / Q000628:therapy*; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008115:Liver Regeneration; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar