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Cell Therapy Trials in Congenital Heart Disease
1From the Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital, Japan. hidemasa@okayama-u.ac.jp.
Insights
Congenital heart disease (CHD) treatments have advanced, but long-term complications persist. Research into mammalian heart regeneration, particularly in early childhood, suggests potential for novel stem cell therapies to treat heart failure in CHD patients.
Area of Science:
- Cardiology
- Regenerative Medicine
- Pediatric Heart Disease
Background:
- Medical advancements have increased survival for children with congenital heart disease (CHD), leading to a rise in long-term complications.
- Heart failure, particularly in single-ventricle lesions like hypoplastic left heart syndrome, remains a significant challenge in CHD.
- Pathophysiological differences exist between pediatric and adult heart disease progression.
Purpose of the Study:
- To explore the potential of regenerative therapies for treating heart failure in patients with congenital heart disease.
- To investigate the mechanisms of cardiac self-repair and their applicability to human heart regeneration.
- To identify novel therapeutic strategies beyond transplantation and mechanical support for advanced cardiac failure in CHD.
Main Methods:
- Review of existing literature on medical and catheter interventions for CHD.
- Examination of studies on cardiac regeneration in lower vertebrates (newt, zebrafish) and mammals (mice).
- Analysis of stem cell therapy case reports and clinical trials in patients with CHD and adult heart disease.
Main Results:
- Mammalian heart regeneration, though declining with age, is most prominent in early childhood.
- Partial ventricular resection in mice confirmed intrinsic cardiac self-repair mechanisms.
- Clinical translation of stem cell therapies for adult heart disease remains inconclusive, but trials in CHD patients show promise.
Conclusions:
- Stem cell therapy holds potential for ameliorating ventricular dysfunction in congenital heart disease patients, especially given the regenerative capacity in early life.
- Understanding the distinct mechanisms of ventricular dysfunction in children versus adults is crucial for developing effective regenerative therapies.
- Future regenerative technologies offer exciting prospects for managing congenital heart disease.
Abstract:
Dramatic evolution in medical and catheter interventions and complex surgeries to treat children with congenital heart disease (CHD) has led to a growing number of patients with a multitude of long-term complications associated with morbidity and mortality. Heart failure in patients with hypoplastic left heart syndrome predicated by functional single ventricle lesions is associated with an increase in CHD prevalence and remains a significant challenge. Pathophysiological mechanisms contributing to the progression of CHD, including single ventricle lesions and dilated cardiomyopathy, and adult heart disease may inevitably differ. Although therapeutic options for advanced cardiac failure are restricted to heart transplantation or mechanical circulatory support, there is a strong impetus to develop novel therapeutic strategies. As lower vertebrates, such as the newt and zebrafish, have a remarkable ability to replace lost cardiac tissue, this intrinsic self-repair machinery at the early postnatal stage in mice was confirmed by partial ventricular resection. Although the underlying mechanistic insights might differ among the species, mammalian heart regeneration occurs even in humans, with the highest degree occurring in early childhood and gradually declining with age in adulthood, suggesting the advantage of stem cell therapy to ameliorate ventricular dysfunction in patients with CHD. Although effective clinical translation by a variety of stem cells in adult heart disease remains inconclusive with respect to the improvement of cardiac function, case reports and clinical trials based on stem cell therapies in patients with CHD may be invaluable for the next stage of therapeutic development. Dissecting the differential mechanisms underlying progressive ventricular dysfunction in children and adults may lead us to identify a novel regenerative therapy. Future regenerative technologies to treat patients with CHD are exciting prospects for heart regeneration in general practice.