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Engineered immunosuppressive dendritic cells protect against cardiac remodelling

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Why This Matters

This research highlights the potential of engineered immunosuppressive dendritic cells (iCDCs) to protect against adverse cardiac remodeling after myocardial infarction. By modulating immune responses and reducing fibrosis, these cells could pave the way for innovative therapies to improve heart function and patient outcomes. The findings underscore the importance of immune-based strategies in cardiovascular treatment development.

Key Takeaways

a, Western blot analysis of FAP protein expression in cardiac tissue at days 1, 3, 7, 14, and 28 post-MI. b, Quantitative RT-PCR analysis of Fap mRNA level in heart and major organs at baseline and indicated time points post-MI, normalized to sham-operated hearts. c, Western blot analysis of FAP protein expression in hearts at day 1, 3, 7, 14, and 28 post-I/R. n = 6 mice per group in a–c. d, Immunofluorescence staining demonstrating co-localization of FAP (green) with vimentin+ fibroblasts (red) in peri-infarct regions at days 3 and 7 post-I/R. Nuclei, DAPI (blue). Scale bars, 50 μm. e, f, Representative M-mode echocardiograms and quantification of EF%, FS%, LVIDd and LVIDs at days 1 and 28 after I/R in mice treated with iCDCs on day 1 (D1), day 3 (D3) or day 7 (D7). n = 8 mice in iCDC (D1) and iCDC (D3), n = 9 mice in other three groups. g, Sirius Red staining and fibrosis quantification at day 28 post-I/R. n = 6 mice per group. Scale bar, 2 mm. h–j, Dose-response analysis comparing low-dose (1.5 × 106) and high-dose (3.0 × 106) iCDC therapy after I/R. Representative echocardiograms, functional quantification and fibrosis analysis are shown. Sham, n = 7 mice; I/R, n = 11 mice; iCDC Low, n = 10 mice; iCDC High, n = 11 mice; fibrosis, n = 6 mice per group. Scale bar, 2 mm. k, l, Flow cytometry and ELISA validation of engineered DC phenotypes and IL-10/CTLA4-Ig secretion in culture (n = 3 biological replicates). m–o, Ex vivo fluorescence imaging of DiR-labelled DCs with quantification (n = 3 mice per group). p, Flow cytometry validation of FAP scFv expression in cultured WTDC, VecDC, CPIDC, and iCDC. q, r, Representative M-mode echocardiograms and quantification of LVIDd and LVIDs at day 3 and day 28 post-MI. n = 10 mice in Sham group, and n = 15 mice in other four groups. s, Kaplan-Meier survival curves for MI mice treated with VecDC or iCDC. n = 29 mice in MI group, and n = 25 mice in VecDC and iCDC groups. t, u, Representative M-mode echocardiograms and quantification of LVIDd and LVIDs at 3 days, 4 weeks, 8 weeks, and 12 weeks post-I/R. Sham, n = 8 mice; I/R, n = 11 mice; VecDC, n = 10 mice; iCDC, n = 10 mice. v, w, Immunofluorescence (n = 6 mice per group) and transcriptomic analyses showing enhanced angiogenesis in iCDC-treated hearts. Data are shown as mean ± s.e.m. (b, f, i, l, n, q) or mean ± s.d. (a, c, g, j, t, u). All statistical tests are two-sided; one-way ANOVA with Tukey’s multiple-comparisons test (a, c, g, j, l, u), two-way ANOVA with Tukey’s multiple-comparisons test (b, f, i, q, t), and Kaplan–Meier survival analysis (r). Source data for immunoblots are provided in Supplementary Fig. 1.

Source data