A new peer-reviewed publication from the DREAMS project is now available in Stem Cell Research, reporting the generation and characterisation of three induced pluripotent stem cell (iPSC) lines derived from patients with Duchenne muscular dystrophy (DMD).
The study provides new patient-derived cellular resources for investigating DMD-associated biology and evaluating potential therapeutic approaches. It also contributes to an important part of the DREAMS research strategy: developing well-characterised biological models from which researchers can generate the experimental data needed for subsequent stages of the project.
Three new patient-derived iPSC lines for DMD research
Duchenne muscular dystrophy is a rare X-linked disorder caused by mutations in the DMD gene, resulting in the absence of functional dystrophin.
Dystrophin is a key component of the protein complex connecting the intracellular cytoskeleton to the extracellular matrix in muscle cells. Its loss contributes to increased membrane fragility and the progressive degeneration of skeletal and cardiac muscle.
To investigate disease-associated biological processes under controlled laboratory conditions, researchers need relevant experimental models.
This is where induced pluripotent stem cells can play an important role.
iPSCs are generated by reprogramming specialised adult cells into a pluripotent state. They can then be expanded and, under appropriate conditions, differentiated towards different cell types.
For rare disease research, this provides a valuable experimental resource: patient-derived iPSCs retain the genetic background of the individual from whom the original cells were obtained and can provide a renewable source of cells for further research.
In the new study, researchers generated three iPSC lines, ISTEMi018-A, ISTEMi019-A and ISTEMi022-A, from peripheral blood mononuclear cells (PBMCs) collected from three male patients with DMD.
The PBMCs were reprogrammed using Sendai viral vectors carrying four reprogramming factors: OCT3/4, SOX2, KLF4 and c-MYC.
How were the new cell lines characterised?
Generating an iPSC line is only the beginning. Before these cells can support subsequent experimental research, it is important to verify that the reprogramming process has preserved their identity, genomic stability and key pluripotent stem cell characteristics.
The researchers therefore performed several levels of characterisation and quality control.
All three lines displayed typical pluripotent stem cell morphology and normal 46,XY karyotypes.
The researchers assessed their undifferentiated state using established pluripotency markers. Immunocytochemistry showed expression of OCT4 and NANOG, while flow cytometry demonstrated high expression of SSEA-4 and TRA-1-81.
They also verified the genetic identity of the generated iPSC lines against the corresponding donor blood cells. Short tandem repeat profiling was used for ISTEMi018-A and ISTEMi019-A, while SNP analysis was used for ISTEMi022-A.
The presence of patient-specific DMD mutations was also verified in the generated lines.
Researchers then assessed the cells’ ability to differentiate towards the three embryonic germ layers. Expression of lineage-specific markers confirmed differentiation potential towards mesoderm, endoderm, and ectoderm.
Finally, the three cell lines tested negative for mycoplasma contamination, and RT-PCR confirmed the absence of residual Sendai viral vectors used during reprogramming.
Together, these analyses establish the identity, pluripotency, genomic stability and differentiation potential of the three patient-derived iPSC lines.
How does this research contribute to DREAMS?
DMD is one of the five rare neuromuscular disorders investigated within DREAMS, together with dynamin 2-related centronuclear myopathy, Emery-Dreifuss muscular dystrophy, Pompe disease and Danon disease.
These diseases were selected because they share pathophysiological characteristics related to autophagy dysfunction. DREAMS is investigating whether studying biological commonalities across these disorders can help identify shared disease mechanisms and, ultimately, potential therapeutic strategies.
Patient-derived cellular models form an early part of this research pipeline.
Within DREAMS, iPSC models can subsequently be differentiated into skeletal muscle cells for disease-relevant studies. The project’s research plan includes investigating disease-associated phenotypes and autophagy-related dysfunctions, generating transcriptomic and proteomic data, and performing phenotypic drug screening.
The distinction between these different stages is important.
The new publication reports the generation and characterisation of three DMD iPSC lines. It does not report results from the project’s downstream drug screening or AI-supported analyses.
Instead, the study provides characterised cellular resources that can support subsequent experimental research.
Building the biological foundation for AI-supported research
DREAMS brings together experimental biology and artificial intelligence, but these components do not operate independently.
The project’s AI approaches are designed to use biological and screening data generated during the experimental stages of the research to investigate questions such as shared drug targets and potential additional disease indications.
That means there is an important sequence behind the DREAMS methodology:
Patient samples → iPSC generation → cellular characterisation → disease-relevant experimental models → biological and screening data → AI-supported analysis
Developing well-characterised cellular resources therefore contributes to the experimental foundation required for the later stages of the project.
This publication captures one part of that process for Duchenne muscular dystrophy.
A new resource for the wider DMD research community
The relevance of the three cell lines is not limited to their role within DREAMS.
As the authors explain, these patient-derived iPSC lines constitute a human cellular resource that can be used to study disease-related cellular phenotypes, explore pathogenic mechanisms and evaluate potential therapeutic approaches.
The three lines are registered in the Human Pluripotent Stem Cell Registry (hPSCreg) as ISTEMi018-A, ISTEMi019-A and ISTEMi022-A.
The publication does not report a new treatment for Duchenne muscular dystrophy. Instead, it provides something that comes much earlier in the research process: characterised patient-derived cellular resources that can enable further investigation.
For DREAMS, this biological foundation is particularly important. By progressively connecting cellular models with experimental data, phenotypic screening and AI-supported analysis, the project is investigating how different approaches can be combined to study rare neuromuscular disorders and potential therapeutic strategies.
Read the new DREAMS publication
Generation and characterization of three human induced pluripotent stem cell lines from patients with Duchenne muscular dystrophy
Hamel Mahiou, Benjamin Marande, Lina El Kassar, Matthieu Lejars, Hassan Hayat, Christelle Kabore, Laura Brulle-Soumare, Pierre Joanne, Onnik Agbulut, Nejette Lallouche, Karim Wahbi, Teresinha Evangelista, Myriam Mederic, Sandrine Baghdoyan, Céline Bruge, Xavier Nissan, Karine Giraud-Triboult and Quentin Miagoux.
Stem Cell Research, Volume 95 (2026), 104074.
DOI: 10.1016/j.scr.2026.104074
The publication is available Open Access under a CC BY licence.
The study was conducted as part of the DREAMS project.
Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor HaDEA can be held responsible for them.
