The Therapeutic Potential of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly in the Treatment of Rat Liver Fibrosis

被引：160

作者：

Tsai, Pei-Chun ^{[1
]}

Fu, Tz-Win ^{[5
]}

Chen, Yi-Ming Arthur ^{[2
]}

Ko, Tsui-Ling ^{[8
]}

Chen, Tien-Hua ^{[3
]}

Shih, Yang-Hsin ^{[6
]}

Hung, Shih-Chieh ^{[4
,7
]}

Fu, Yu-Show ^{[3
,9
]}

机构：

[1] Natl Yang Ming Univ, Sch Med, Inst Anat & Cell Biol, Taipei 112, Taiwan

[2] Natl Yang Ming Univ, Sch Med, Inst Microbiol & Immunol, Taipei 112, Taiwan

[3] Natl Yang Ming Univ, Sch Med, Dept Anat & Cell Biol, Taipei 112, Taiwan

[4] Natl Yang Ming Univ, Sch Med, Inst Clin Med, Taipei 112, Taiwan

[5] Taipai Vet Gen Hosp, Dept Lab Med, Taipei, Taiwan

[6] Taipai Vet Gen Hosp, Neurol Inst, Dept Neurosurg, Taipei, Taiwan

[7] Taipai Vet Gen Hosp, Stem Cell Lab, Taipei, Taiwan

[8] Taipei Med Univ, Sch Med, Dept Anat, Taipei, Taiwan

[9] Taipei City Hosp, Dept Educ & Res, Taipei, Taiwan

来源：

LIVER TRANSPLANTATION | 2009年 / 15卷 / 05期

关键词：

HEPATOCYTE-LIKE CELLS; HEPATIC STELLATE CELLS; BONE-MARROW-CELLS; NEURONS IN-VITRO; CORD BLOOD; STROMAL CELLS; TGF-BETA; MICE; TRANSPLANTATION; REGENERATION;

D O I：

10.1002/lt.21715

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs) from Wharton's jelly on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats were treated with CCl4 for 4 weeks, and this was followed by a direct injection of HUMSCs into their livers. After 4 more weeks of CCl4 treatment (8 weeks in all), rats with HUMSC transplants [CCl4 (8W)+HUMSC liver] exhibited a significant reduction in liver fibrosis, as evidenced by Sirius red staining and a collagen content assay, in comparison with rats treated with CCl4 for 8 weeks without HUMSC transplants [CCl4 (8W)]. Moreover, rats in the CCl4 (8W)+HUMSC (liver) group had significantly lower levels of serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, alpha-smooth muscle actin, and transforming growth factor-beta 1 in the liver, whereas the expression of hepatic mesenchymal epithelial transition factor-phosphorylated type (Met-P) and hepatocyte growth factor was up-regulated, in comparison with the CCl4, (8W) group. Notably, engrafted HUMSCs scattered mostly in the hepatic connective tissue but did not differentiate into hepatocytes expressing human albumin or alpha-fetoprotein. Instead, these engrafted, undifferentiated HUMSCs secreted a variety of bioactive cytokines that may restore liver function and promote regeneration. Human cytokine assay revealed that the amounts of human cutaneous T cell-attracting chemokine, leukemia inhibitory factor, and prolactin were substantially greater in the livers of the CCl4 (8W)+HUMSC (liver) group, with considerably reduced hepatic inflammation manifested by a micro positron emission tomography scan. Our findings suggest that xenogeneic transplantation of HUMSCs is a novel approach for treating liver fibrosis and may be a promising therapeutic intervention in the future. Liver Transpl 15: 484-495, 2009. (C) 2009 AASLD.

引用

页码：484 / 495

页数：12

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