Fig 2: Dose-dependent therapeutic effects of LNP/sisFRP2 in a mouse model of US.a A representative TEM image of LNP/sisFRP2 (n = 6 samples). b A workflow depicts the treatment protocols. In these experiments, female mice were euthanized at day 30 post-uterine scarring and subsequent interventions. Control, mice subjected to a low abdominal incision without uterine incision; Model, mice with US induced by uterine scar surgery and receiving topical saline treatment; LNP/sisFRP2, US mice treated with LNP/sisFRP2 at 0.125, 0.25, and 0.5 mg/kg of sisFRP2. c Immunohistochemical analysis of sFRP2 in uterine tissues from different groups (n = 6 mice). d–g mRNA levels of sFRP2 (d) fibrinogen (e) Col1A1 (f) and Col3A1 (g) in uterine tissues from different groups. h H&E-stained uterine tissue sections for different groups (n = 6 mice). The black arrows indicate uterine glands. Box plots in d–g illustrate data distributions (n = 6 mice), with the central lines representing the mean, box boundaries indicating standard deviation, and whiskers showing the minimum and maximum values. The p values were calculated by one-way ANOVA with post hoc LSD tests. Source data are provided as a Source Data file.

Fig 3: Effects of sFRP2 overexpression in the mouse uterine tissue on scar formation-related biomarkers, histological structures of the uterus, and scar transformation of isolated mUFIBs.a A flowchart shows the induction of sFRP2 overexpression (sFRP2OE) in the uterine tissue of mice, with control animals receiving negative control lentivectors. b–g WB detection (b, c), qPCR quantification (d), and immunohistochemistry analysis (e–g, n = 6 mice) of sFRP2, VEGFA, and α-SMA in the mouse uterine tissues after 7 days of sFPR2OE intervention. The red arrows in f indicate neovascularization. h, i Histological sections of mouse uterine tissues stained with Masson’s trichrome or H&E (n = 6 mice). j WB analysis of fibrinogen, Col1A1, and Col3A1 levels in uterine tissues of sFRP2OE mice and control mice. k A diagram details the isolation of mUFIBs from both control and sFRP2OE mice. l Microscopic images and quantification of migrated mUFIBs from control and sFRP2OE groups. m Digital images (left) and quantitative analysis (right) assess the contractility of mUFIBs, with white circles marking the collagen boundary after 24 h of incubation. Box plots in c, d, l, m illustrate data distributions (n = 6 mice), with the central lines representing the mean, box boundaries indicating standard deviation, and whiskers showing the minimum and maximum values. The p values were calculated by two-tailed unpaired t-tests. Source data are provided as a Source Data file.

Fig 4: Expression of sFRP2 and biomarkers associated with the scar formation in various cells isolated from the normal and scarred uteruses.a A diagram depicting isolation of hUSMCs, hUFIBs, and hUECs from human uterine tissues. b, c Representative WB bands (b) and quantitative analysis (c) of sFRP2 in hUSMCs, hUFIBs, and hUECs sourced from both normal and US cohorts. d mRNA levels of sFRP2 in hUSMCs, hUFIBs, and hUECs. e WB analysis of protein expression profiles of sFRP2, VEGFA, and α-SMA in hUFIBs. f Quantified mRNA expression levels of sFRP2, VEGFA, and α-SMA in hUFIBs. g, h WB analysis (g) and qPCR quantification (h) of fibrinogen, Col1A1, and Col3A1 in hUFIBs. i, j Immunofluorescence analysis of the co-distribution of sFRP2 with α-SMA (i), Col3A1, or Col1A1 (j) in hUFIBs (n = 6 samples). k Microscopic images of migrated hUFIBs. l Digital photos show collagen gel contractility assay of hUFIBs, with white circles marking the collagen periphery after 24 h of culture. Data in bar graphs (c, d) are presented as means ± standard deviation (n = 6 samples). Box plots in f, h illustrate data distributions (n = 6 samples), with the central lines representing the mean, box boundaries indicating standard deviation, and whiskers showing the minimum and maximum values. The p values were calculated by two-tailed unpaired t-tests for two groups and one-way ANOVA with post hoc LSD tests for multiple groups. Source data are provided as a Source Data file.

Fig 5: RNA-seq analysis, quantification of scar formation-related biomarkers, and histological examination of uteruses from mice with uterine surgical scarring, as well as analysis of scar transformation of mUFIBs.a A schematic diagram showing the protocol for establishing uterine scars in mice (model), with control animals undergoing a low abdominal incision without uterine incision (control). b, c Heatmap (b) and volcano plots (c) illustrate RNA-seq data comparing mouse uterine tissues from the surgical scar group with the non-scar group (n = 3 mice). d GO analysis showcases the up-regulated GO terms in the model group versus the control group, with blue indicating scar-related pathways and green highlighting Ca2+-related pathways (n = 3 mice). e–i Analysis of sFRP2, VEGFA, and α-SMA in mouse uterine tissues by WB (e) qPCR (f) and immunohistochemistry (g–i, n = 6 mice). Red arrows indicate neovascularization. j, k Microscopic images of mouse uterine tissue sections stained with Masson’s trichrome (j, n = 6 mice) or H&E (k, n = 6 mice). l A workflow depicts the isolation of mUFIBs. m WB analysis of the expression levels of fibrinogen, Col1A1, and Col3A1 in mUFIBs. n, o Immunofluorescence analysis of the co-distribution of sFRP2 with α-SMA (n), Col3A1, and Col1A1 (o) in mUFIBs (n = 6 mice). p Microscopic images of migrated mUFIBs. q Digital photos show the contractility performance of mUFIBs in collagen gel contractility assay. White circles depict the collagen boundary after 24 h of incubation. Box plots in f display data distribution (n = 6 mice), with the central lines representing the mean, box boundaries indicating standard deviation, and whiskers showing the minimum and maximum values. The p values were calculated by two-tailed unpaired t-tests. Source data are provided as a Source Data file.