Brief Article
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World J Gastroenterol. Mar 28, 2013; 19(12): 1984-1991
Published online Mar 28, 2013. doi: 10.3748/wjg.v19.i12.1984
Effect evaluation of interleukin-1 receptor antagonist nanoparticles for mesenchymal stem cell transplantation
Xiao-Lei Shi, Wei Zhu, Jia-Jun Tan, Jiang-Qiang Xiao, Lin Zhang, Qian Xu, Zheng-Liang Ma, Yi-Tao Ding
Xiao-Lei Shi, Jia-Jun Tan, Jiang-Qiang Xiao, Yi-Tao Ding, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Xiao-Lei Shi, Yi-Tao Ding, Key Medical Center of Jiangsu Province for Hepatobiliary Diseases, Nanjing 210008, Jiangsu Province, China
Wei Zhu, Gulou Clinical Medical College of Combined TCM and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China
Wei Zhu, Zheng-Liang Ma, Department of Anesthesiology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Lin Zhang, Qian Xu, School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China
Author contributions: Shi XL and Zhu W contributed equally to this work; Shi XL, Zhu W, Ma ZL and Ding YT designed the research; Zhu W and Tan JJ wrote the paper; Xiao JQ, Zhang L and Xu Q performed the research; Tan JJ and Xu Q did data analysis.
Supported by National Natural Science Foundation of China, No. 30901431
Correspondence to: Yi-tao Ding, Professor, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing 210008, China. yitaoding@hotmail.com
Telephone: +86-25-83105502 Fax: +86-25-83107080
Received: September 21, 2012
Revised: January 20, 2013
Accepted: February 5, 2013
Published online: March 28, 2013
Abstract

AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF).

METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction; Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.

RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45- MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.

CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.

Keywords: Interleukin-1 receptor antagonist, Mesenchymal stem cells, Cell transplantation, Acute liver failure, Inflammatory environment