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Background and Objectives@#Mesenchymal stem cells (MSCs) elicit therapeutic effects against liver fibrosis in animal models. Human liver stem cells (HLSCs) are cells isolated from human liver tissue that have mesenchymal morphology and express MSC markers. HLSCs also possess intrahepatic stem cell properties. We introduce a rat model of liver fibrosis and trans-portal transplantation of HLSC to demonstrate alleviation of liver fibrosis. @*Methods@#and Results: Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl 4 ). Sprague Dawley rats underwent simultaneous partial hepatectomy of the left hepatic lobe and HLSC transplantation via the portal vein. Gross appearance of the liver observed following CCl 4 injection showed cholestasis and surface nodularity. Sirius red staining revealed deposition of collagen fibers in the extracellular matrix (ECM). Following HLSC transplantation, human albumin secreting cells were detected by immunohistochemistry in liver specimens. Quantitative measurements of fibrosis area stained by Sirius red were compared between baseline and post-HLSC transplant (1×10 7 cells) following 10 weeks of CCl 4treatment liver specimens. Fibrosis area (p＜0.05), serum markers of liver inflammation and fibrosis (AST, ALT levels and APRI, p＜0.05) significantly decreased from baseline after HLSC transplantation. RNA expression in liver tissues revealed significant decrease in tissue inhibitor of matrix metalloproteinase 1 (TIMP1), TIMP2 expression and increase in hepatocyte growth factor expression following HLSC transplantation (p＜0.05). @*Conclusions@#HLSC transplantation effectively reduced the area of liver fibrosis with increased expression of factors promoting ECM degradation. These findings suggest the potential therapeutic role of HLSCs in various liver diseases presenting with liver fibrosis.
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Corrections for Table. 1 in page 125 are needed. We apologize for any inconvenience that this may have caused.
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PURPOSE: The clinical efficacy of allergen-immunotherapy is known to be dose dependent. However, optimal maintenance dosage has not yet been determined for sublingual immunotherapy (SLIT). Furthermore, since companies adopt their own units for expression of allergenicity, the allergen concentrations of individual reagents cannot be compared easily. We sought to measure and compare the allergenicities of 3 commercially available house dust mite (HDM) SLIT regents and a subcutaneous immunotherapy reagent. METHODS: We measured the HDM allergenic potency of the maintenance dosages of three SLIT reagents: Staloral(R) (300 index of reactivity [IR] /mL, recommended maintenance dosage [MD]: 120 IR), SLITone(R) (1,000 standard therapeutic unit [STU]/mL, recommended MD: 200 STU), Wolwopharma(R) (100 microg/mL, recommended MD: 20 microg), and subcutaneous immunotherapy regents of Hollister-Stier (10,000 allergy unit [AU] /mL). The allergenic potency was assessed by measuring the total protein concentrations, mite group 1 and 2 allergens using 2-site ELISA, and an inhibition test against IgE specific to Dermatophagoides farinae and Dermatophagoides pteronyssinus. RESULTS: The protein content of the Wolwopharma(R) reagent was 1.5-261.4 times higher than that of the other 2 SLIT reagents. The concentration of group 1 major allergens in Staloral(R) (132.03 microg/mL) was 33- to 44.5-fold higher than in SLITone(R) (4.00 microg/mL) and Wolwopharma(R) (2.97 microg/mL). The concentration of group 2 major allergen was also 8.9- to 10.5-fold higher in Staloral(R) (15.7 microg/mL) than in SLITone(R) (1.8 microg/mL) or Wolwopharma(R) (1.5 microg/mL). An ELISA inhibition study against HDM-specific IgE showed that the allergen potency of Staloral(R) reagent is 8.5-fold and 21-fold higher than that of SLITone(R) or Wolwopharma(R), respectively. The differences between the maintenance dosages are further exaggerated by the differences in the recommended volumes of SLIT reagents. CONCLUSIONS: The allergen potencies of commercially available HDM SLIT reagents are markedly different. Consensus regarding the optimal allergen concentration for SLIT reagents used to treat HDM respiratory allergies is needed.