ArticleStem cell research & therapy2026
CAR-T cells targeting fibroblast activation protein eliminate pathological fibroblasts and preserve cardiac function in a Duchenne Muscular Dystrophy murine model.
Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundChimeric Antigen Receptor (CAR)-T cells therapy has revolutionized the treatment of hematological cancers and are currently redirected towards non-malignant diseases. If correction of the gene defect remains the cornerstone of the treatment of Duchenne Muscular Dystrophy (DMD), the disease-associated fibrosis can limit its efficacy. We thus assessed the effects of eliminating cardiac fibrosis of DMD by CAR-T cells targeting Fibroblast Activation Protein (FAP), a protein strongly expressed by activated fibroblasts.
methodsIn vitro CAR-T cells expressing both FAP and a green fluorescent probe (GFP) were first co-cultured with FAP + of FAP- target cells to check for FAP-expressing lymphocyte activation. Then, anti-FAP CAR-T cells were intravenously delivered in a dystrophic murine model (D2.mdx), following lymphodepletion, to investigate the kinetics, biodistribution, cardiac functional and anti-fibrotic effects of anti-FAP CAR-T cells compared with control lymphocytes engineered to only express GFP. The mechanism of action at a cellular level was assessed by single-cell RNA-sequencing of harvested hearts.
resultsIn vitro anti-FAP CAR-T cells were successfully activated when co-cultured with FAP + target cells. In a dystrophic murine model (D2.mdx), anti-FAP CAR-T cells, intravenously delivered following lymphodepletion, homed to the heart and skeletal muscles, where they decreased FAP and fibrosis-associated genes. Single-cell RNA-sequencing linked these changes to a decrease in a definite cluster of fibrogenic fibroblasts. Concomitantly, anti-FAP CAR-T cells improved cardiac function compared to control mice injected with GFP-transduced T lymphocytes or bovine serum albumin used as negative controls.
conclusionsThese results suggest that anti-FAP CAR-T cells could be efficient for mitigating fibrosis and thus complement gene therapy of DMD. More generally, their therapeutic benefits pave the way for potential applications extending to other fibrosis-associated diseases.
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