title: Effect evaluation of interleukin-1 receptor antagonist nanoparticles for mesenchymal stem cell transplantation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Tan
authors.forename: Jiang-Qiang
authors.initials: JQ
authors.lastname: Xiao
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Zheng-Liang
authors.initials: ZL
authors.lastname: Ma
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000473:pathology / Q000628:therapy*; D008111:Liver Function Tests; D045164:Mesenchymal Stem Cell Transplantation; D053758:Nanoparticles; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D013552:Swine
chemical_list: D016207:Cytokines; D017472:Receptors, Interleukin-1
keywords: Acute liver failure; Cell transplantation; Inflammatory environment; Interleukin-1 receptor antagonist; Mesenchymal stem cells