Localization and therapeutic effect of bone marrow hematopoietic cell transplantation in rat model of liver fibrosis / 临床肝胆病杂志

ABSTRACT

ObjectiveTo investigate the localization and therapeutic effect of allogeneic bone marrow hematopoietic stem cell (HSC) transplantation in the rat model of liver fibrosis induced by carbon tetrachloride (CCl4). MethodsBone marrow HSCs from allogeneic Sprague-Dawley (SD) rats were isolated and cultured in vitro and labeled with 5-bromo-2′-deoxyuridine (BrdU) before transplantation. Eighteen female SD rats were randomly and equally divided into groups A, B, and C. A female rat model of liver fibrosis was established using CCl4. The rats in group A were injected with HSC-containing suspension through the caudal vein in the fourth week after CCl4 injection, while the rats in groups B and C were injected with normal saline through the caudal vein. In the eighth week, blood samples were taken from all groups. Then all rats were sacrificed, and the liver, pancreatic, and stomach tissues were collected to examine the localization of HSC and evaluate the therapeutic effect of HSC on liver damage. The double-blind method was used to statistically analyze experimental results. Comparison of continuous data between these groups was made by analysis of variance, and pairwise comparison was made by SNK-q test; comparison of categorical data between these groups was made by Kruskal-Wallis H test, and pairwise comparison was made by Nemenyi test. ResultsGroup A showed significantly improved histopathology compared with group B, while groups A and C showed approximately the same histological findings. There were significant differences in classification of liver fibrosis between groups A, B, and C (χ2=13.14, P=0.001), and groups A and C had significantly lower grades of liver fibrosis than group B (both P＜0.05). In group A, BrdU-positive cells were detected in the liver tissues of all rats, but no positive cells were detected in the pancreatic and stomach tissues; no BrdU-positive cells were detected in groups B and C. Compared with group B, groups A and C had significantly lower alanine aminotransferase and aspartate aminotransferase levels but a significantly higher albumin level (all P＜0.05). ConclusionAllogeneic HSC can be localized in the rat model of liver fibrosis and reverse the liver damage.