Bone marrow cell transplant does not prevent or reverse murine liver cirrhosis.
We tested the effect of bone marrow cell (BMC) transplantation in either preventing or reversing cirrhosis on an experimental model of chronic liver disease. Female Wistar rats were fed a liquid alcohol diet and received intraperitoneal injections of carbon tetrachloride (CCl4) over 15 weeks. Ten animals (cell-treated group) received five injections of BMCs during the cirrhosis induction protocol (on the 4th, 6th, 8th, 10th, and 12th weeks) and four animals received the cells after liver injury was established through tail vein. Nine animals (nontreated group) were submitted to the previously described protocols; however, they received vehicle injections. Analyses were performed to verify whether the infusion of cells was effective in preventing the development of cirrhosis in our model of induction, and if the cells could reverse cirrhosis once it was established. Hepatic architecture and fibrotic septa were analyzed in liver slices stained with hematoxilin & eosin and Sirius red, respectively. Fibrosis quantification was measured by Sirius red histomorphometry. Indirect immunofluorescence was performed to detect the amount of tissue transglutaminase 2. Blood analyses were performed to assess liver injury and function by the assessment of alanine aminotransferase and albumin. Ultrasound was performed to analyze the portal vein caliber and presence of ascitis. Cirrhosis features (regenerative nodules and fibrous septa) were observed in histopathology after 15 weeks of continuous hepatic injury in nontreated and cell-treated groups. Collagen content, immunofluorescence analysis, and biochemical and ultrasound parameters were similar in nontreated and cell-treated groups; however, both groups showed significant differences compared to a normal control group. Cell infusions with bone marrow-derived cells seem to be ineffective in improving morphofunctional parameters of the liver when applied to chronic cases either during or after establishment of the hepatic lesion.
Quintanilha
L F
LF
Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, 21941-902, Brazil.
Mannheimer
E G
EG
Carvalho
A B
AB
Paredes
B D
BD
Dias
J V
JV
Almeida
A S
AS
Gutfilen
B
B
Barbosa da Fonseca
L M
LM
Resende
C M C
CM
Rezende
G F M
GF
Campos de Carvalho
A C
AC
Goldenberg
R C S
RC
D000418:Albumins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds; D016026:Bone Marrow Transplantation / Q000379:methods*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002492:Central Nervous System Depressants / Q000633:toxicity; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004396:Coloring Agents; D004195:Disease Models, Animal; D004798:Enzymes / Q000032:analysis / Q000378:metabolism; D004801:Eosine Yellowish-(YS); D000431:Ethanol / Q000633:toxicity; D005260:Female; D006416:Hematoxylin; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000601:surgery; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011169:Portal Vein / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014463:Ultrasonography
D000418:Albumins; D001391:Azo Compounds; D002492:Central Nervous System Depressants; D004396:Coloring Agents; D004798:Enzymes; C000717609:Tgm2 protein, rat; D000431:Ethanol; C062246:Direct Red 81; D003094:Collagen; D002251:Carbon Tetrachloride; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin