Stem cell therapy for hypoplastic left heart syndrome: a systematic review of efficacy, safety, and future directions
Bibliographic record
Abstract
Abstract Background Hypoplastic Left Heart Syndrome (HLHS) is a severe congenital heart disease characterized by underdevelopment of the left heart structures, often requiring staged surgical palliation. Despite improvements in surgical management, HLHS is associated with high mortality and long-term morbidity. Stem cell-based therapies have emerged as a promising adjunct to improve cardiac function and outcomes in these patients. Objectives This systematic review evaluates the long-term safety and efficacy of stem cell therapy, particularly cardiosphere-derived cells (CDCs) and umbilical cord blood-derived mononuclear cells (UCB-MNCs), in the treatment of HLHS. Methods Following PRISMA guidelines, a comprehensive search was conducted across major databases. Seven studies met the inclusion criteria, comprising randomized controlled trials, observational cohorts, and in vitro analyses. Quality appraisal was performed using RoB2, Newcastle–Ottawa, and SYRCLE tools. Results Stem cell therapy was associated with improvements in right ventricular ejection fraction, somatic growth, heart failure status, and psychosocial quality of life. CDCs showed favorable outcomes in both early and long-term follow-up, with reductions in scar burden, ventricular volume, and adverse events. Importantly, no major adverse effects such as arrhythmias, systemic infections, or tumor formation were reported. The use of allogeneic cells could extend beyond HLHS to other forms of congenital heart disease with right ventricular dysfunction, including tetralogy of Fallot, pulmonary atresia, and other single-ventricle variants. In vitro studies confirmed the regenerative capacity of pediatric-derived stem cells, with the highest potential in the first year of life. Conclusion Stem cell therapy demonstrates safety, feasibility, and potential efficacy in improving cardiac outcomes in HLHS. Larger, multicenter trials such as the APOLLON trial are warranted to validate these findings and support integration into standard clinical care.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.024 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.008 |
| Bibliometrics | 0.005 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".