Fig. 2: HGF + EGF mRNA-LNP treatments augment PHH engraftment by increasing the survival and proliferation of donor cells in p21/NSG-PiZ mice. | Nature Communications

Fig. 2: HGF + EGF mRNA-LNP treatments augment PHH engraftment by increasing the survival and proliferation of donor cells in p21/NSG-PiZ mice.

From: Transient growth factor expression via mRNA in lipid nanoparticles promotes hepatocyte cell therapy in mice

Fig. 2

a PHH transplantation experimental timeline and treatment groups. A single IV dose of AAV8-TBG-p21 was injected one week prior to cell transplantation, while mRNA-LNP were administered IV 5 h before transplantation and twice weekly for 2 weeks. Cryopreserved PHHs were thawed and transplanted into male NSG-PiZ mice via intrasplenic injection of 106 cells/mouse. Four groups were used: control Luc mRNA-LNP only, AAV8-TBG-p21 only, HGF + EGF mRNA-LNP only, and the combined group with both p21 and HGF + EGF injections. Recipient mice were given an EdU injection and sacrificed 2 weeks post transplantation, serum was collected weekly, and liver tissue harvested for analysis. b Representative images of hALB/Ku80/EdU immunofluorescence stain on liver sections 2 weeks post transplantation. c Quantification of the number of hALB+ Ku80+ PHH clusters per 10x image. d Quantification of the number of hALB+ Ku80+ PHHs per cluster. e Quantification of the number of hALB+ Ku80+ EdU+ proliferating PHHs per cluster. f Quantification of co-stained hALB+ Ku80+ area per 10x image. For all histology quantification c–f at least three images were averaged per mouse, each image from a different liver lobe. P values were calculated by unpaired two-sided student’s t test. g Human serum albumin levels measured via ELISA over the course of 2-week transplantation experiments. P values were calculated by ordinary one-way ANOVA. For all panels: n = 5 mice per group except in p21 only group where n = 4 mice as specified in figure key, each dot represents one mouse, error bars = SEM, scale = 100 µm, ns P > 0.05, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. Yellow—control, green—p21 only, teal—HGF + EGF only, blue—p21 & HGF + EGF treated group. Source data are provided as a Source Data file. a Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.

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