Cell Therapy for Duchenne Muscular Dystrophy: Promises, Challenges, and Controversies

Major Points and Findings:

This narrative review was written by two laboratory researchers at the Jagiellonian University in Kraków, who declare no financial interests. It was not conducted as a systematic review and contains no new patient data on Duchenne muscular dystrophy (DMD). We include it because it is the most critical recent assessment of the field. The authors are sceptical of mesenchymal stromal cells (MSCs), including the umbilical cord cells that clinics such as ours use, and families weighing up treatment should be able to read that argument in full.

The authors’ position is that cell therapy for DMD is not an established treatment. Approaches with a sound biological rationale (satellite cells, mesoangioblasts, muscle cells made from pluripotent stem cells) have so far failed on delivery and engraftment, and several approaches already offered to patients lack, in their view, a sound rationale altogether.

Aim:

To summarise recent progress in cell therapies for DMD, identify the barriers, and critically examine approaches the authors consider questionable.

Methods:

The paper is a narrative review of about 200 references. No search strategy, inclusion criteria or quality grading are described, so the selection and weighting of evidence reflect the authors’ judgement. It covers how DMD damages the muscle’s own stem cells, current drug and genetic treatments, each family of cell therapy, cell therapy for the heart, and other muscular dystrophies.

Results:

The authors describe five barriers. They start from the premise that only cells able to become skeletal muscle can give meaningful benefit. Any such therapy must:

• produce enough undifferentiated muscle progenitor cells to repopulate a very large mass of tissue
• avoid rejection if donor cells are used, which normally means immunosuppression
• restore dystrophin first if the patient’s own cells are used
• avoid an immune reaction against dystrophin itself
• engraft long-term across many muscles, which in practice requires delivery through the bloodstream

Myoblasts and satellite cells: Early myoblast transfer trials were negative overall. Even with more than 100 million cells and multiple injections, the cells failed to engraft because of immune rejection, poor migration from the injection site and their already differentiated state. Given intravenously, such cells are trapped in the lungs. In a macaque study of intra-arterial delivery only about 3.2% of injected cells were found in muscle. The authors conclude that giving myoblasts through the bloodstream is not justified by the evidence.

Mesoangioblasts are vessel-associated cells that looked promising in dystrophic mice and dogs. In the one clinical trial, five DMD patients received four intra-arterial infusions of HLA-matched cells from healthy siblings at 2-month intervals, with tacrolimus immunosuppression. Muscle biopsies two months after the last infusion showed only low levels of donor DNA in 4 of 5 patients and dystrophin in one.

Muscle cells made from pluripotent stem cells are, in the authors’ view, the most credible route because the cells can be precisely defined. A table lists 17 animal experiments showing engraftment and, in some, functional improvement. There are caveats. Results usually depended on first injuring the muscle with cardiotoxin or irradiation, which could not be done in patients. Unsorted cells formed teratomas in one study, and systemic delivery remains inefficient.

Mesenchymal “stem” cells: The authors argue that:

• MSCs from bone marrow can form fat, cartilage and bone, but claims that they form skeletal or heart muscle have been challenged and often put down to flaws in the experiments.
• In a rigorous transplantation study from Bianco’s group, CD146-positive stromal cells from human muscle formed myoblasts, while equivalent cells from bone marrow, periosteum and cord blood did not.
• Reports of benefit from adipose-derived MSCs in mdx mice and dystrophic dogs have not been repeated by others.
• On Wharton’s jelly cells, citing another review, they state that published outcomes point to these cells being ineffective in DMD.
• They object that such cells are sold commercially for many conditions without regulation or proof.

The MSC section of the review does not discuss the alternative argument, that these cells might help through anti-inflammatory and anti-scarring signals without becoming muscle. Nor does it analyse individual clinical MSC studies in DMD. Its verdict rests on the requirement that a useful cell must form muscle.

Chimeric cells (DT-DEC01): The authors consider this approach even less justified than MSCs. They say the animal work used models that cannot reject cells, never showed the cells entering the circulation from bone, and ignores the evidence that myoblasts do not leave blood vessels to enter muscle. The published patient reports are open and non-randomised, so in their view the results cannot count as evidence of a treatment effect. They cite a public warning from the patient organisation World Duchenne and argue that raising false hope can do more harm than offering no treatment.

The heart and cardiosphere-derived cells: The authors summarise HOPE-Duchenne (25 patients, intracoronary delivery) and HOPE-2, and raise three concerns. These are the hypersensitivity reactions that forced a change to mandatory pre-treatment, the exosome mechanism, which they regard as unproven, and the FDA’s refusal to approve the product in July 2025.

In other muscular dystrophies, work in limb-girdle dystrophies and FSHD is almost entirely preclinical. One phase I/IIa trial (bASKet, NCT05588401) is testing gene-corrected autologous satellite cells in six limb-girdle patients. The exception is oculopharyngeal muscular dystrophy. In 12 patients given injections of their own healthy myoblasts into the throat muscles, there were no adverse effects over 2 years and swallowing improved in 10.

Conclusions:

The authors conclude that, unlike bone marrow transplantation, where diseased cells are cleared out first, cells given in DMD enter a hostile environment of chronic inflammation, scarring and ongoing muscle death, and the volume of tissue to be treated is enormous. They suggest that combining cell therapy with anti-inflammatory and anti-scarring treatment is a rational next step.

The review lists no limitations of its own. The main ones are the lack of a systematic method and a brief treatment of MSCs that leans on other reviews.

Background Information:

Two points in the review need updating or correcting.

• The review was published in October 2025, before HOPE-3 reported. That 106-patient placebo-controlled trial of deramiocel met its primary endpoint for arm function in July 2026, although its key heart endpoint did not reach significance. The review’s concern about hypersensitivity was borne out (41.5% of treated participants against 15.4% on placebo).
• The review’s account of HOPE-2 does not match the original Lancet paper. It says six of the twelve placebo patients were excluded for screening failures. In the Lancet paper, six boys failed screening before randomisation and 12 were then randomised to placebo. The review calls the hypersensitivity reactions in three patients serious adverse events, whereas HOPE-2 reported one severe reaction among the three.

A cell therapy for DMD should be judged on controlled evidence that it changes the course of the disease, and no MSC product has yet shown that in DMD. Families can reasonably ask any provider what the cells are expected to do, since there is no good evidence that MSCs become muscle or supply dystrophin.