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PLoS One. 2018 Oct 24;13(10):e0206311. doi: 10.1371/journal.pone.0206311. eCollection 2018.

Intratracheal transplantation of mesenchymal stem cells attenuates hyperoxia-induced lung injury by down-regulating, but not direct inhibiting formyl peptide receptor 1 in the newborn mice.

Kim YE1,2, Park WS2,3,4, Ahn SY2,3, Sung DK2,4, Chang YS1,2,3,4.

Author information

1
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea.
2
Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, Korea.
3
Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
4
Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

Formyl peptide receptor 1 (FPR1) has been shown to be a key regulator of inflammation. However, its role in bronchopulmonary dysplasia (BPD) has not been delineated yet. We investigated whether FPR1 plays a pivotal role in regulating lung inflammation and injuries, and whether intratracheally transplanted mesenchymal stem cells (MSCs) attenuate hyperoxic lung inflammation and injuries by down-regulating FPR1. Newborn wild type (WT) or FPR1 knockout (FPR1-/-) C57/BL6 mice were randomly exposed to 80% oxygen or room air for 14 days. At postnatal day (P) 5, 2×10(5) MSCs were intratracheally transplanted. At P14, mice were sacrificed for histopathological and morphometric analyses. Hyperoxia significantly increased lung neutrophils, macrophages, and TUNEL-positive cells, while impairing alveolarization and angiogenesis, along with a significant increase in FPR1 mRNA levels in WT mice. The hyperoxia-induced lung inflammation and lung injuries were significantly attenuated, with the reduced mRNA level of FPR1, in WT mice with MSC transplantation and in FPR1-/- mice, irrespective of MSCs transplantation. However, only MSC transplantation, but not the FPR1 knockout, significantly attenuated the hyperoxia-induced increase in TUNEL-positive cells. Our findings indicate that FPR1 play a critical role in regulating lung inflammation and injuries in BPD, and MSCs attenuate hyperoxic lung inflammation and injuries, but not apoptosis, with down regulating, but not direct inhibiting FPR1.

PMID:
30356317
PMCID:
PMC6200259
DOI:
10.1371/journal.pone.0206311
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

We have the following interests: Human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs) were supplied by MEDIPOST Co, Ltd; the sponsor had no involvement in study design, the collection, analysis, or interpretation of data; writing of the report; or the decision to submit the manuscript for publication. Samsung Medical Center and MEDIPOST Co, Ltd have piled patents for “Method of treating lung diseases using cells separated or proliferated from umbilical cord blood” under names of Yun Sil Chang, Won Soon Park and Yoon Sun Yang (not affiliated with this article) (Korean Patent No.10-0837167, US Patent No.US 9,498,497 B2, Canadian Patent No. 2,640,728, Singapore Patent No. 144446, Japanese Patent No.5112336). Also, Samsung Medical Center and Busan University issued “Role of formyl peptide receptor 1 in hyperoxic lung injury after intratracheal transplantation of hUCB-MSCs in newborn mice” under names of Yun Sil Chang, Won Soon Park, So Yoon Ahn, Dong Kyung Sung, Young Eun Kim and Jae Ho Kim (KR10-2018-0051692). In addition, Samsung Medical Center have filed “Composition for treating intraventricular hemorrhage in preterm infants comprising mesenchymal stem cells” under names of Yun Sil Chang and Won Soon Park (Korean Patent No. 10-1405620, US Patent No. 9,539,285,) and filed and issued “Composition for treating inflammatory brain disease, which includes stem cell as active ingredient under names of Yun Sil Chang and Won Soon Park (Korean Patent No 10-1654970, EU14754748.3 and US 14/768,734). Young Eun Kim and Yun Sil Chang are employed by Samsung Advanced Institute for Health Sciences and Technology (SAIHST). Won Soon Park, Ahn So Yoon, Dong Kyung Sung and Yun Sil Chang are employed by Samsung Medical Center. Won Soon Park, Dong Kyung Sung and Yun Sil Chang are employed by Samsung Biomedical Research Institute. Won Soon Park received other commercial funds not related to this article from MEDIPOST Co. Ltd. (PHO0140131, HO0133531, PHO0181901). There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

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