Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats

Authors: Yu Wang, Fan Lian, Jiaping Li, Wenzhe Fan, Hanshi Xu, Xiuyan Yang, Liuqin Liang, Wei Chen, Jianyong Yang

Published in: Journal of Translational Medicine | Issue 1/2012

Login to get access

Abstract

Introduction

Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway.

Methods

ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4)-induced liver fibrosis rats. Computed tomography (CT) perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated.

Results

CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII) immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF) was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein.

Conclusions

ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.
Appendix
Available only for authorised users
Literature
1.
2.
Gines P, Cardenas A, Arroyo V: Management of cirrhosis and ascites. N Engl J Med. 2004, 350: 1646-1654.CrossRefPubMed
3.
4.
Fallowfield JA, Iredale JP: Targeted treatments for cirrhosis. Expert Opin Ther Targets. 2004, 8: 423-425.CrossRefPubMed
5.
Ortiz LA, Gambelli F, McBride C: Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A. 2003, 100 (14): 8407-8411.CrossRefPubMedPubMedCentral
6.
Sakaida I, Terai S, Yamamoto N: Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004, 40 (6): 1304-1311.CrossRefPubMed
7.
Deans RJ, Moseley AB: Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000, 28: 875-884.CrossRefPubMed
8.
Liang L, Ma T, Chen W: Therapeutic potential and related signal pathway of adipose-derived stem cell transplantation for rat liver injury. Hepatol Res. 2009, 39 (8): 822-832.CrossRefPubMed
9.
Schaffler A, Buchler C: Concise review: adipose tissue-derived stromal cells—basic and clinical implications for novel cell-based therapies. Stem Cells. 2007, 25 (4): 818-827.CrossRefPubMed
10.
Khan WS, Adesida AB, Tew SR: The epitope characterization and the osteogenic differentiation potential of human fat pad-derived stem cells is maintained with ageing in later life. Injury. 2009, 40 (2): 150-157.CrossRefPubMed
11.
Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M: Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy. 2006, 8: 166-177.CrossRefPubMed
12.
Safford KM, Hicok KC, Safford SD: Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun. 2002, 294: 371-379.CrossRefPubMed
13.
Mitchell JB, Mclntosh K, Zvonic S: Immnophenotype of Human Adipose-Derived Cells: Temporal Changes in Stromal-Associated and Stem Cell-Associated Markers. Stem Cells. 2006, 24: 376-385.CrossRefPubMed
14.
Aurich H, Sgodda M, Kaltwasser P: Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut. 2009, 58 (4): 570-581.CrossRefPubMed
15.
Liu F, Liu ZD, Wu N: Transplanted endothelial progenitor cells ameliorate carbon tetrachloride-induced liver cirrhosis in rats. Liver Transpl. 2009, 15 (9): 1092-1100.CrossRefPubMed
16.
Dong MX, Jia Y, Zhang YB: Emodin protects rat liver from CCl4-induced fibrogenesis via inhibition of hepatic stellate cells activation. World J Gastroenterol. 2009, 15 (38): 4753-4762.CrossRefPubMedPubMedCentral
17.
Varga F, Mehes G, Molnar Z: Reversibility of hepatic fibrosis induced by carbon tetrachloride in the rat. Acta Physiol Acad Sci Hung. 1996, 29: 69-74.
18.
Materne R, Van Beers BE, Smith AM: Non-invasive quantification of liver perfusion with dynamic computed tomography and a dual-input one-compartmental model. Clin Sci (Lond). 2000, 99: 517-525.CrossRef
19.
Van Beers BE, Leconte I, Materne R: Hepatic perfusion parameters in chronic liver disease: dynamic CT measurements correlated with disease severity. Am J Roentgenol. 2001, 176: 667-673.CrossRef
20.
Yang ZF, Ho DW, Chu AC: Linking inflammation in small-for-size allografts: the potential role of early macrophage activation. Am J Transplant. 2004, 4: 196-CrossRefPubMed
21.
Liu MY, Poellinger L, Walker CL: Up-regulation of hypoxia-inducible factor 2alpha in renal cell carcinoma associated with loss of Tsc-2 tumor suppressor gene. Cancer Res. 2003, 63: 2675-2680.PubMed
22.
Gandhi CR, Kuddus RH, Nemoto EM: Endotoxin treatment causes an up-regulation of the endothelin system in the liver: Amelioration of increased portal resistance by endothelin receptor antagonism. J Gastroenterol Hepatol. 2001, 16: 61-69.CrossRefPubMed
23.
Sun CK, Chang CL, Lin YC: Systemic administration of autologous adipose-derived mesenchymal stem cells alleviates hepatic ischemia-reperfusion injury in rats. Crit Care Med. 2012, 40 (4): 1279-1290.CrossRefPubMed
24.
Yukawa H, Noguchi H, Oishi K: Cell transplantation of adipose tissue-derived stem cells in combination with heparin attenuated acute liver failure in mice. Cell Transplant. 2009, 18 (5): 611-618.PubMed
25.
Abdel aziz MT, EI Asmar MF, Atta HM: Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling. J Exp Clin Cancer Res. 2011, 30: 49-CrossRefPubMedPubMedCentral
26.
Baertschiger RM, Bosco D, Morel P: Mesenchymal stem cells derived from human exocrine pancreas express transcription factors implicated in beta-cell development. Pancreas. 2008, 37 (1): 75-84.CrossRefPubMed
27.
Meyerrowe TE, De Ugarte DA, Hofling AA: In vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models. Stem Cells. 2007, 25 (1): 220-227.CrossRef
28.
Ren H, Zhao Q, Cheng T: No contribution of umbilical cord mesenchymal stromal cells to capillarization and venularization of hepatic sinusoids accompanied by hepatic differentiation in carbon tetrachloride-induced mouse liver fibrosis. Cytotherapy. 2010, 12 (3): 371-383.CrossRefPubMed
29.
Lee KD, Kuo TK, Whang-Peng J: In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology. 2004, 40 (6): 1275-1284.CrossRefPubMed
30.
Oyagi S, Hirose M, Kojima M: Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats. J Hepatol. 2006, 44 (4): 742-748.CrossRefPubMed
31.
Aquino JB, Bolontrade MF, García MG: Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma. Gene Ther. 2010, 17 (6): 692-708.CrossRefPubMed
32.
Ishikawa T, Terai S, Urata Y: Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice. Cell Tissue Res. 2007, 327 (3): 463-470.CrossRefPubMed
33.
Kamada Y, Yoshida Y, Saji Y: Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice. Am J Physiol Gastrointest Liver Physiol. 2009, 296 (2): G157-G167.CrossRefPubMed
34.
Rabani V, Shahsavani M, Gharavi M: Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression. Cell Biol Int. 2010, 34 (6): 601-605.CrossRefPubMed
35.
Miles KA, Hayball MP, Dixon AK: Functional images of hepatic perfusion obtained with dynamic CT. Radiology. 1993, 88: 405-411.CrossRef
36.
Pulavendran S, Vignesh J, Rose C: Differential anti-inflammatory and anti-fibrotic activity of transplanted mesenchymal vs. hematopoietic stem cells in carbon tetrachloride-induced liver injury in mice. Int Immunopharmacol. 2010, 10 (4): 513-519.CrossRefPubMed
37.
Moioli EK, Paul A: Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. PLoS One. 2008, 31 (12): e3922-CrossRef
38.
Kestendjieva S, Kyukchiev D, Tsvetkova G: Characterization of mesenchymal stem cells isolated from the human umbilical cord. Cell Biol Int. 2008, 32: 724-732.CrossRefPubMed
39.
Yue WM, Liu W, Bi YW: Mesenchymal stem cells differentiate into an endothelial phenotype, reduce neointimal formation, and enhance endothelial function in a rat vein grafting model. Stem Cells Dev. 2008, 17: 785-794.CrossRefPubMed
40.
Tang J, Xie Q, Pan G: Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg. 2006, 30: 353-361.CrossRefPubMed
41.
Rosmorduc O, Wendum D, Corpechot C: Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis. Am J Pathol. 1999, 155: 1065-1073.CrossRefPubMedPubMedCentral
42.
Cui S, Hano H, Sakata A: Enhanced CD34 expression of sinusoid-like vascular endothelial cells in hepatocellular carcinoma. Pathol Int. 1996, 46: 751-756.CrossRefPubMed
43.
Ishikawa K, Mochida S, Mashiba S: Expressions of vascular endothelial growth factor in nonparenchymal as well as parenchymal cells in rat liver after necrosis. Biochem Biophys Res Commun. 1999, 254: 587-593.CrossRefPubMed
44.
Arthur MJ, Mann DA, Iredale JP: Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis. J Gastroenterol Hepatol. 1998, 13 (suppl): S33-S38.PubMed
45.
Ankoma-Sey V, Wang Y, Dai Z: Hypoxic stimulation of vascular endothelial growth factor expression in activated rat hepatic stellate cells. Hepatology. 2000, 31: 141-148.CrossRefPubMed
46.
Raleigh JA, Calkins-Adams DP, Rinker LH: Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker. Cancer Res. 1998, 58: 3765-3768.PubMed
47.
Shi BM, Wang XY, Mu QL: Expression of vascular endothelial growth factor in cirrhotic tissues and their relations to proto-oncogene c-fos, c-myc. Hepatobiliary Pancreat Dis Int. 2002, 1 (3): 388-391.PubMed
48.
Kim SJ, Park KC, Lee JU: Therapeutic potential of adipose tissue-derived stem cells for liver failure according to the transplantation routes. J Korean Surg Soc. 2011, 81 (3): 176-186.CrossRefPubMedPubMedCentral
49.
Bos C, Delmas Y, Desmouliere : In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology. 2004, 233: 781-789.CrossRefPubMed
50.
Yu Y, Lu L, Qian X: Antifibrotic effect of hepatocyte growth factor expressing mesenchymal stem cells in a smal-for-size liver transplant rats. Stem Cells Dev. 2010, 19 (6): 93-03-14-CrossRef
51.
Chang YJ, Liu JW, Lin PC: Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis. Life Sci. 2009, 85 (13–14): 517-525.CrossRefPubMed
Metadata
Title
Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats
Authors
Yu Wang
Fan Lian
Jiaping Li
Wenzhe Fan
Hanshi Xu
Xiuyan Yang
Liuqin Liang
Wei Chen
Jianyong Yang
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-133

Other articles of this Issue 1/2012

Journal of Translational Medicine 1/2012 Go to the issue

Research

Chemokine CXCL12 activates dual CXCR4 and CXCR7-mediated signaling pathways in pancreatic cancer cells

Research

The application of observational data in translational medicine: analyzing tobacco-use behaviors of adolescents

Research

Specifically targeting ERK1 or ERK2 kills Melanoma cells

Review

Nerve growth factor: from the early discoveries to the potential clinical use

Research

Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats

Research

Copper-transporting P-type adenosine triphosphatase (ATP7A) is associated with platinum-resistance in non-small cell lung cancer (NSCLC)
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits