3D bioprinted myocardium patches for rare Barth syndrome - TAZ mutation correction in cardioblasts

Sep 29, 2026

Letter to the editor discussing an ultra-rare genetic disorder, Barth syndrome, driven by inactivating TAZ gene (tafazzin) mutations that disrupt cardiolipin remodeling and impair mitochondrial bioenergetics, leading to dilated cardiomyopathy, neutropenia, and growth retardation. It outlines a regenerative approach using 3D bioprinted myocardium patches made from patient-derived iPSC cardioblasts, with CRISPR/Cas9 editing to restore TAZ expression. Reported preclinical and early safety findings include high biomarker correction and improved cardiac function, while challenges in cost, manufacturing, regulation, and long-term safety require further studies and international collaboration.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Background: Barth syndrome and TAZ-driven cardiolipin dysfunction

Regenerative strategy: 3D bioprinted myocardium patches with gene editing

Evidence of potential efficacy and safety

Barriers to clinical adoption

Conclusion and future directions

Letter to the Editor 3D bioprinted myocardium patches for rare Barth syndrome: TAZ mutation correction in cardioblasts Aiman Tahir, MBBSa , Eashaal Imtiaz, MBBSb , Raghabendra Kumar Mahato, MBBSc ,* To the Editor, Barth syndrome (BS) is an ultra-rare X-linked genetic disorder primarily characterized by mutations in the TAZ gene (Tafazzin) . It results in severe cardioskeletal myopathy, recurrent neutropenia, and growth retardation. The syndrome is fundamentally caused by inactivating TAZ mutations, which are crucial for remodeling mitochondrial lipid, cardiolipin. Defective cardiolipin metabolism leads to mitochondrial dysfunction, impaired cellular bioenergetics, and progressive dilated cardiomyopathy, along with skeletal muscle weakness and neutropenia[1] . The global prevalence of BS is approximated to be about 1 in 300,000– 400,000 live births, presenting a high fatality rate in early childhood. Genetic testing for TAZ mutations, echocardiography, and mitochondrial function assays are the predominant diagnostic approaches[2] . The field of regenerative medicine offers a promising intervention: 3D bioprinted myocardium patches. This treatment manages BS by correcting the causative TAZ mutation inpatient-derived cardioblasts. It involves deposition of bio-ink containing patient-derived induced pluripotent stem cell (iPSC) cardioblasts onto a biomimetic scaffold. The technique involves precise layering of TAZ-corrected cardioblasts within a biocompatible scaffold to promote tissue remodeling and electrical conductivity. The emphasis is on correcting the TAZ gene using CRISPR/Cas9 gene editing to restore effective TAZ gene expression in cardioblasts. The efficacy of this treatment relies on effective cell engraftment, improved cardiac function, and prolonged survival. Initial studies have shown encouraging success and improvements in myocardial contractility. While bioprinted patches are chiefly being investigated for the treatment of BS, similar patches are under development for managing acute aDepartment of Medicine, Azad Jammu and Kashmir Medical College, Muzaffarabad, Pakistan, bDepartment of Medicine, Ayub Medical College, Abbottabad, Pakistan and cDepartment of Medicine, Gandaki Medical College Teaching Hospital and Research Center, Pokhara, Nepal Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department of Medicine, Gandaki Medical College Teaching Hospital and Research Center Pokhara 33700, Nepal. Tel.: +977 9745829807. E-mail: [102raghabendrakumarmahato@gmail.com](102raghabendrakumarmahato@gmail.com)[ ](102raghabendrakumarmahato@gmail.com)(R.K. Mahato). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This isan open access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Annals of Medicine & Surgery (2026) 88:1096–1097 Received 9 November 2025; Accepted 18 November 2025 Published online 25 November 2025 [http://dx.doi.org/10.1097/MS9.0000000000004456](http://dx.doi.org/10.1097/MS9.0000000000004456) myocardial infarction, refractory heart failure, and congenital defects[3] . Combined clinical literature supports the synergistic application of gene therapy and bioengineered myocardial scaffolds. Studies modeling BS with iPSC-derived cardioblasts have demonstrated that TAZ-corrective gene editing enhances mitochondrial integrity and restores cardiolipin structure (MLCL/CL ratio) mid-way through experimental workflows[4] . Once organized into a 3D bioprinted myocardial patch, the constructs demonstrated a striking 91 ± 3% correction of the pathogenic monolysocardiolipin to cardiolipin (MLCL/CL) biomarker ratio, leading to

FAQs

What causes Barth syndrome and why is TAZ important?

Barth syndrome results from inactivating mutations in the TAZ (tafazzin) gene, which are crucial for remodeling mitochondrial lipid cardiolipin. Defective cardiolipin metabolism contributes to mitochondrial dysfunction and progressive dilated cardiomyopathy, alongside skeletal muscle weakness and neutropenia.

How do 3D bioprinted myocardium patches aim to treat rare Barth syndrome?

The approach deposits patient-derived iPSC cardioblasts into a biomimetic scaffold using precise 3D layering. CRISPR/Cas9 gene editing is used to correct the TAZ mutation so cardioblasts can restore effective TAZ gene expression, promoting tissue remodeling and electrical conductivity.

What limitations could slow clinical adoption of this therapy?

The letter highlights high costs and required technical expertise, the need for longitudinal safety studies, gaps in scalable good manufacturing practice and regulatory standardization, and limited clinical awareness for integrating such therapies into routine practice.

Sep 29, 2026

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