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Published on: October 19, 2013
Fresh Noncultured Endothelial Progenitor Cells Improve Neonatal Lung Hyperoxia-Induced Alveolar Injury
Alexandra B Firsova1, A Daniel Bird1, Degu Abebe1
1Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Insights
Fresh bone marrow endothelial progenitor cells (EPCs) fully restored lung development in neonatal mice exposed to high oxygen. Cultured EPCs showed partial recovery but also aberrant growths, suggesting fresh EPCs are safer for hyperoxia-induced lung injury.
Area of Science:
- Regenerative Medicine
- Neonatal Lung Development
- Cell Therapy
Background:
- High oxygen exposure in preterm infants disrupts lung alveolar and vascular development.
- Endothelial progenitor cells (EPCs) show promise in animal models for repairing such damage.
Purpose of the Study:
- To investigate the effects of fresh and cultured bone marrow (BM)-derived EPCs on hyperoxia-induced lung injury in neonatal mice.
- To compare the efficacy and safety of fresh versus cultured EPCs in a neonatal lung injury model.
Main Methods:
- Neonatal mice were exposed to 90% oxygen to induce lung injury.
- Intraperitoneal injections of fresh or cultured BM-derived EPCs were administered.
- Lung alveolarization and vascular development were assessed at 28 and 56 days post-injection.
Main Results:
- Fresh EPCs led to full recovery of alveolar disruption by 56 days.
- Short-term cultured EPCs provided partial recovery, while long-term cultured EPCs induced aberrant tissue growths.
- Fresh and long-term cultured EPCs did not impact blood vessel development; short-term cultured EPCs transiently increased blood vessel number.
Conclusions:
- Fresh BM EPCs demonstrate a superior and safer corrective profile for hyperoxia-induced lung injury compared to cultured EPCs.
- Cultured EPCs may cause detrimental side effects, including aberrant tissue growths, requiring further investigation.
- Fresh EPCs may negatively impact alveolarization in normoxic conditions.
Abstract:
Treatment of preterm human infants with high oxygen can result in disrupted lung alveolar and vascular development. Local or systemic administration of endothelial progenitor cells (EPCs) is reported to remedy such disruption in animal models. In this study, the effects of both fresh (enriched for KDR) and cultured bone marrow (BM)-derived cell populations with EPC characteristics were examined following hyperoxia in neonatal mouse lungs. Intraperitoneal injection of fresh EPCs into five-day-old mice treated with 90% oxygen resulted in full recovery of hyperoxia-induced alveolar disruption by 56 days of age. Partial recovery in septal number following hyperoxia was observed following injection of short-term cultured EPCs, yet aberrant tissue growths appeared following injection of long-term cultured cells. Fresh and long-term cultured cells had no impact on blood vessel development. Short-term cultured cells increased blood vessel number in normoxic and hyperoxic mice by 28 days but had no impact on day 56. Injection of fresh EPCs into normoxic mice significantly reduced alveolarization compared with phosphate buffered saline-injected normoxic controls. These results indicate that fresh BM EPCs have a higher and safer corrective profile in a hyperoxia-induced lung injury model compared with cultured BM EPCs but may be detrimental to the normoxic lung. The appearance of aberrant tissue growths and other side effects following injection of cultured EPCs warrants further investigation. Stem Cells Translational Medicine 2017;6:2094-2105.
