Effect evaluation of interleukin-1 receptor antagonist nanoparticles for mesenchymal stem cell transplantation.
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.
['Shi|Xiao-Lei|XL|', 'Zhu|Wei|W|', 'Tan|Jia-Jun|JJ|', 'Xiao|Jiang-Qiang|JQ|', 'Zhang|Lin|L|', 'Xu|Qian|Q|', 'Ma|Zheng-Liang|ZL|', 'Ding|Yi-Tao|YT|']
D000818:Animals D003131:Combined Modality Therapy D016207:Cytokines D008099:Liver D017114:Liver Failure, Acute D008111:Liver Function Tests D045164:Mesenchymal Stem Cell Transplantation D053758:Nanoparticles D017472:Receptors, Interleukin-1 D013552:Swine
Interleukin-1 receptor antagonist Mesenchymal stem cells Cell transplantation Acute liver failure Inflammatory environment