Therapeutic Potential of Endothelial Progenitor Cells in Pulmonary Diseases
Olena A Kolesnichenko1, Jeffrey A Whitsett2,3, Tanya V Kalin2,3
1Center for Lung Regenerative Medicine, and.
Insights
Endothelial progenitor cells (EPCs) offer hope for treating pediatric lung diseases like bronchopulmonary dysplasia (BPD) and alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) by promoting vascularization. Research into EPC markers and in vitro generation shows promise for regenerative therapies.
Area of Science:
- Pediatric Pulmonology
- Vascular Biology
- Regenerative Medicine
Background:
- Pediatric lung diseases, including bronchopulmonary dysplasia (BPD) and alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), are characterized by impaired alveolar development and pulmonary vascular remodeling.
- Current treatments for preterm infants have limitations, and severe vascular complications remain a significant challenge, particularly in ACDMPV where poor vascularization leads to high mortality.
- Endothelial progenitor cells (EPCs), discovered in 1997, represent a promising avenue for promoting postnatal vasculogenesis and addressing vascular deficiencies in these conditions.
Purpose of the Study:
- To review the biology of endothelial progenitor cells (EPCs), including hematopoietic, nonhematopoietic, and tissue-resident populations.
- To identify key cell surface markers, gene expression patterns, and transcriptional regulators associated with EPCs.
- To explore the translational potential of EPCs for developing cell-based therapies for pediatric lung diseases like BPD and ACDMPV.
Main Methods:
- Review of existing literature on EPC biology and function.
- Analysis of cell surface markers, gene expression profiles, and transcriptional regulators of various EPC populations.
- Examination of the potential for in vitro generation of pulmonary EPCs from induced pluripotent stem cells.
Main Results:
- Identification of diverse EPC populations with distinct origins (hematopoietic, nonhematopoietic, tissue-resident).
- Understanding of specific markers and genetic regulators crucial for EPC properties.
- Demonstration of the potential for generating functional EPCs in vitro from patient-derived stem cells.
Conclusions:
- EPCs hold significant promise for regenerative medicine in pediatric lung disorders.
- Targeting EPCs and their properties could lead to novel cell-based therapies for BPD and ACDMPV.
- In vitro generation of pulmonary EPCs offers a potential strategy to restore vascular growth and function in affected lungs.
Abstract:
Compromised alveolar development and pulmonary vascular remodeling are hallmarks of pediatric lung diseases such as bronchopulmonary dysplasia (BPD) and alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). Although advances in surfactant therapy, corticosteroids, and antiinflammatory drugs have improved clinical management of preterm infants, those who suffer with severe vascular complications still lack viable treatment options. Paucity of the alveolar capillary network in ACDMPV causes respiratory distress and leads to mortality in a vast majority of infants with ACDMPV. The discovery of endothelial progenitor cells (EPCs) in 1997 brought forth the paradigm of postnatal vasculogenesis and hope for promoting vascularization in fragile patient populations, such as those with BPD and ACDMPV. The identification of diverse EPC populations, both hematopoietic and nonhematopoietic in origin, provided a need to identify progenitor cell-selective markers that are linked to progenitor properties needed to develop cell-based therapies. Focusing on the future potential of EPCs for regenerative medicine, this review will discuss various aspects of EPC biology, beginning with the identification of hematopoietic, nonhematopoietic, and tissue-resident EPC populations. We will review knowledge related to cell surface markers, signature gene expression, and key transcriptional regulators and will explore the translational potential of EPCs for cell-based therapy for BPD and ACDMPV. The ability to produce pulmonary EPCs from patient-derived induced pluripotent stem cells in vitro holds promise for restoring vascular growth and function in the lungs of patients with pediatric pulmonary disorders.
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