Unlocking the potential of induced pluripotent stem cells for neonatal disease modeling and drug development
Ziyi Liu1, Bonny Lami1, Laertis Ikonomou2
1Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Center for Stem Cell and Organoid Medicine, CuSTOM, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, United States.
Insights
Human induced pluripotent stem cells (hiPSCs) offer a personalized approach for studying and treating neonatal heart and lung diseases. These cells can be differentiated into various cell types for disease modeling and drug screening, paving the way for novel regenerative therapies.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Neonatal Diseases
Background:
- Neonatal heart and lung diseases, including Congenital Heart Disease (CHD), are rare but can lead to severe long-term health issues.
- These conditions often stem from complex genetic and environmental factors, necessitating innovative treatment strategies.
Approach:
- Human induced pluripotent stem cells (hiPSCs) provide a unique platform for disease modeling, drug screening, and cell-based therapies for neonatal cardiovascular and pulmonary conditions.
- iPSCs can be differentiated into various cardiac and lung cell types (e.g., cardiomyocytes, Type II alveolar epithelial cells) to investigate disease mechanisms in vitro.
- This review explores the application of hiPSCs in understanding the pathology of CHD and congenital lung diseases.
Key Points:
- hiPSCs facilitate the study of molecular mechanisms and cellular phenotypes in conditions like structural heart defects, congenital valve disease, and surfactant deficiencies.
- The potential to generate mature cell types and advanced 3D models (organoids, tissue-engineered constructs) from iPSCs is crucial for future research.
- hiPSC-derived cells and models enable high-throughput drug screening for identifying novel therapeutic compounds.
Conclusions:
- hiPSCs hold significant promise for advancing the treatment of congenital heart and lung diseases in neonates.
- Future directions include enhancing cell maturation and utilizing sophisticated hiPSC-based systems for improved therapeutic development.
- The potential for hiPSC-derived therapies offers hope for improved outcomes in affected newborns.
Abstract:
Neonatal lung and heart diseases, albeit rare, can result in poor quality of life, often require long-term management and/or organ transplantation. For example, Congenital Heart Disease (CHD) is one of the most common type of congenital disabilities, affecting nearly 1% of the newborns, and has complex and multifactorial causes, including genetic predisposition and environmental influences. To develop new strategies for heart and lung regeneration in CHD and neonatal lung disease, human induced pluripotent stem cells (hiPSCs) provide a unique and personalized platform for future cell replacement therapy and high-throughput drug screening. Additionally, given the differentiation potential of iPSCs, cardiac cell types such as cardiomyocytes, endothelial cells, and fibroblasts and lung cell types such Type II alveolar epithelial cells can be derived in a dish to study the fundamental pathology during disease progression. In this review, we discuss the applications of hiPSCs in understanding the molecular mechanisms and cellular phenotypes of CHD (e.g., structural heart defect, congenital valve disease, and congenital channelopathies) and congenital lung diseases, such as surfactant deficiencies and Brain-Lung-Thyroid syndrome. We also provide future directions for generating mature cell types from iPSCs, and more complex hiPSC-based systems using three-dimensional (3D) organoids and tissue-engineering. With these potential advancements, the promise that hiPSCs will deliver new CHD and neonatal lung disease treatments may soon be fulfilled.
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