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World J Gastroenterol. 2013 Mar 28;19(12):1984-91. doi: 10.3748/wjg.v19.i12.1984.

Effect evaluation of interleukin-1 receptor antagonist nanoparticles for mesenchymal stem cell transplantation.

Author information

1
Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.

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 × 10(8) 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:

Acute liver failure; Cell transplantation; Inflammatory environment; Interleukin-1 receptor antagonist; Mesenchymal stem cells

PMID:
23569345
PMCID:
PMC3613115
DOI:
10.3748/wjg.v19.i12.1984
[Indexed for MEDLINE]
Free PMC Article
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