| Title: |
Patient-Derived 3D Bioprinted Cardiac Organoid Constructs Reveal Key Pathological Features of Duchenne Muscular Dystrophy |
| Authors: |
Marini, Vittoria; Campaner Socias, Margalida; Dimopoulos, Andreas; Rinvenuto, Lorenza; Pozzo, Enrico; Stalkopf, Diana; Serafini, Angelo; Morri, Sara; Wang, Ashley; La Rovere, Rita; Chai, Yoke Chin; Bollini, Sveva; Bultynck, Geert; Roderick, H. Llewelyn; Papantoniou, Ioannis; Sampaolesi, Maurilio |
| Source: |
ISSN:2192-2640 ; ISSN:2192-2659 ; Advanced Healthcare Materials. |
| Publisher Information: |
Wiley |
| Publication Year: |
2026 |
| Subject Terms: |
Science & Technology; Technology; Engineering; Biomedical; Nanoscience & Nanotechnology; Materials Science; Biomaterials; Science & Technology - Other Topics; alginate; bioprinting; cardiac organoids; cardiomyopathies; Duchenne muscular dystrophy; gelatin; MICROTISSUES; 2020-EMR116: INTERREG Euregio Meuse-Rhine; 0304 Medicinal and Biomolecular Chemistry; 0903 Biomedical Engineering; 1004 Medical Biotechnology; 3206 Medical biotechnology; 4003 Biomedical engineering |
| Description: |
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration that significantly reduces the quality of life and lifespan of patients. Currently, cardiomyopathy represents the leading cause of death in later stages of the disease. While calcium dysregulation, fibrosis, and fat deposits are well-documented hallmarks of DMD cardiomyopathies, the exact pathogenic mechanisms remain unclear due to the lack of reliable models. In this study, we developed 3D cardiac organoids (COs) from DMD patient-derived induced pluripotent stem cells (DMD-hiPSCs), their isogenic control (DMD-Iso-hiPSCs), and a healthy hiPSC line (HC-hiPSCs). By day 15 of cardiac differentiation, DMD-COs exhibited key disease features, including increased cell death, elevated ROS levels, and calcium signaling defects, compared with controls. Leveraging bioprinting technology, COs were embedded in a 7% alginate-5% gelatin hydrogel to generate bioprinted constructs (HC-bCOs, DMD-Iso-bCOs, and DMD-bCOs). These constructs self-organized, displaying increased cell-cell communication, and reduced levels of the early cardiac transcription factor NKX2.5. By day 14 post-bioprinting, DMD-bCOs showed increased cell death and dysregulated expression of cardiac and fibrotic markers, mimicking DMD-associated cardiomyopathy. This study demonstrates the potential of both COs and bCOs as a tool for studying DMD cardiomyopathy and advancing drug screening and therapies. ; sponsorship: V.M. and M.C.S. are supported by The Research Foundation Flanders #1S98725N and FWO #1167225N, respectively). M.S. acknowledges funding from FWO (#G058924N), INTERREG - Euregio Meuse-Rhine (GYM, Generate Your Muscle 2020-EMR116), Small Research Infrastructure KU Leuven-BioAssemblyBot 400 (KA/20/088), ERA-NET ERA4Health CARDINNOV: AmnioSMART #G0GE223N, the Ricerca Finalizzata from the Italian Ministry of Health (RF-2019-12369703), and Medium Infrastructure KU Leuven (AKUL/19/34 to GB and MS). H.L.R. thanks KU Leuven Research Council (#C14/21/093) ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/20.500.12942/783026; https://doi.org/10.1002/adhm.202504004; https://pubmed.ncbi.nlm.nih.gov/41677066 |
| DOI: |
10.1002/adhm.202504004 |
| Availability: |
https://lirias.kuleuven.be/handle/20.500.12942/783026; https://hdl.handle.net/20.500.12942/783026; https://lirias.kuleuven.be/retrieve/e288d6bc-3a84-4104-818e-f1ff5aa3b746; https://doi.org/10.1002/adhm.202504004; https://pubmed.ncbi.nlm.nih.gov/41677066 |
| Rights: |
info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.E6F1C9BC |
| Database: |
BASE |