Fig. 4

Therapeutic effects of iHeps on acute liver failure. a Schematic diagram of iHep transplantation into the livers of NPG mice. NPG mice were injected with carbon tetrachloride (CCl ₄ ) to trigger fulminant hepatitis, which led to acute liver failure and death within 24 hours in all mice. Eight hours after CCl₄ treatment, ADSCs, iHeps, and rHeps (2 × 10⁶ cells/animal) were injected into the spleens of the mice. b Kaplan–Meier survival curve of NPG mice with acute liver failure that did not receive cells (sham operation) or received 2 × 10⁶ ADSCs, iHeps, and rHeps. Almost all mice died in groups transplanted with ADSCs or sham operation (one mouse in the sham operation group died at day 2), two of five recipient mice survived after transplantation with iHeps, and three of five mice receiving rHep transplantation survived. Kaplan–Meier survival curve depicted. c, d Serum levels of ALT (c) and AST (d) in CCL₄-treated mice before (day 0) and after (day 7) transplantation of iHeps or rHeps. e Rat ALB levels were determined by ELISA in the sera of surviving NPG mice. f, g Livers in CCl₄-treated mice before (day 0) and after iHep transplantation (day 7). Macroscopic images of freshly isolated livers (f) and hematoxylin and eosin staining of liver sections (g). Note CCl₄-induced hepatitis and hemorrhage in the liver at day 0 (f), arrows in (g). The liver already recovered from CCl₄-induced damage at day 7. h Expression of ALB and AAT in engrafted iHeps revealed by immunofluorescence. The ALB antibody is rat specific and the AAT antibody reacts with both rat and mouse. Data presented as mean ± standard deviation. Scale bar: 5 mm (f), 100 μm (g, h). AAT alpha-1-antitrypsin, ADSC adipose-derived stem cell, ALB albumin, ALT alanine transaminase, AST glutamic-oxaloacetic transaminase, iHep induced functional hepatocyte, PAS Periodic acid–Schiff, rHep primary rat hepatocyte