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To solve this problem, myocardium and nerve tissues were modelled by 3D engineered heart tissues (EHTs) and neural organoids (NOs), which were co\u2010cultured in a generalised medium with normal or elevated glucose\/fatty acid contents. Morphology, gene expression, cell death and functional assessments detected no apparent alterations of EHTs and NOs in co\u2010culture under normal conditions. By contrast, NOs significantly ameliorated glucolipotoxicity in EHTs. Transcriptomic and protein secretion assays identified the extracellular matrix protein versican as a key molecule that was transferred from NOs into EHTs in the high\u2010glucose\/fatty acid condition. Recombinant versican protein treatment was sufficient to reduce glucolipotoxicity in EHTs. Adeno\u2010associated virus\u2010delivered versican overexpression was sufficient to ameliorate cardiac dysfunction in a murine model of diabetic cardiomyopathy. These data provide the proof\u2010of\u2010concept evidence that inter\u2010tissue\/organ communications exist in the co\u2010culture of engineered tissues and organoids, which could be systemically studied to explore potential pathological mechanisms and therapeutic strategies for multi\u2010organ diseases in\u00a0vitro.<\/jats:p>","DOI":"10.1111\/cpr.70070","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T08:58:48Z","timestamp":1748941128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neural Organoids Protect Engineered Heart Tissues From Glucolipotoxicity by Transferring Versican in a Co\u2010Culture System"],"prefix":"10.1111","volume":"59","author":[{"given":"Baochen","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Cardiology Peking University People's Hospital  Beijing 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