Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats
Recent evidence suggests mesenchymal stem cells (MSCs) can downmodulate bleomycin-induced lung injury, and umbilical cord blood (UCB) is a promising source for human MSCs. This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate hyperoxia-i...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2009-08-01
|
Series: | Cell Transplantation |
Online Access: | https://doi.org/10.3727/096368909X471189 |
id |
doaj-db080475310648ca83ba71fd8589f8b3 |
---|---|
record_format |
Article |
spelling |
doaj-db080475310648ca83ba71fd8589f8b32020-11-25T03:22:47ZengSAGE PublishingCell Transplantation0963-68971555-38922009-08-011810.3727/096368909X471189Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal RatsYun Sil Chang0Wonil Oh1Soo Jin Choi2Dong Kyung Sung3Soo Yoon Kim4Eun Yang Choi5Saem Kang6Hye Jin Jin7Yoon Sun Yang8Won Soon Park M.D., Ph.D.9Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seoul, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seoul, KoreaSamsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaSamsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaSamsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaSamsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seoul, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seoul, KoreaSamsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaRecent evidence suggests mesenchymal stem cells (MSCs) can downmodulate bleomycin-induced lung injury, and umbilical cord blood (UCB) is a promising source for human MSCs. This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate hyperoxia-induced lung injury in immunocompetent newborn rats. Wild-type Sprague-Dawley rats were randomly exposed to 95% oxygen or air from birth. In the transplantation groups, a single dose of PKH26-labeled human UCB-derived MSCs was administered either intratracheally (2 × 10 6 cells) or intraperitoneally (5 × 10 5 cells) at postnatal day (P) 5. At P14, the harvested lungs were examined for morphometric analyses of alveolarization and TUNEL staining, as well as the myeoloperoxidase activity, the level of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and transforming growth factor (TGF)-β mRNA, α-smooth muscle actin (SMA) protein, and collagen levels. Differentiation of MSCs to the respiratory epithelium was also evaluated both in vitro before transplantation and in vivo after transplantation. Despite one fourth dosage of MSCs, significantly more PKH26-labeled donor cells were recovered with intratracheal administration than with intraperitoneal administration both during normoxia and hyperoxia. The hyperoxia-induced increase in the number of TUNEL-positive cells, myeloperoixdase activity, and the level of IL-6 mRNA were significantly attenuated with both intratracheal and intraperitoneal MSCs transplantation. However, the hyperoxia-induced impaired alveolarization and increased the level of TNF-α and TGF-β mRNA, α-SMA protein, and collagen were significantly attenuated only with intratracheal MSCs transplantation. MSCs differentiated into respiratory epithelium in vitro and a few PKH26-positive donor cells were colocalized with pro surfactant protein C in the damaged lungs. In conclusion, intratracheal transplantation of human UCB-derived MSCs is more effective than intraperitoneal transplantation in attenuating the hyperoxia-induced lung injury in neonatal rats.https://doi.org/10.3727/096368909X471189 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yun Sil Chang Wonil Oh Soo Jin Choi Dong Kyung Sung Soo Yoon Kim Eun Yang Choi Saem Kang Hye Jin Jin Yoon Sun Yang Won Soon Park M.D., Ph.D. |
spellingShingle |
Yun Sil Chang Wonil Oh Soo Jin Choi Dong Kyung Sung Soo Yoon Kim Eun Yang Choi Saem Kang Hye Jin Jin Yoon Sun Yang Won Soon Park M.D., Ph.D. Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats Cell Transplantation |
author_facet |
Yun Sil Chang Wonil Oh Soo Jin Choi Dong Kyung Sung Soo Yoon Kim Eun Yang Choi Saem Kang Hye Jin Jin Yoon Sun Yang Won Soon Park M.D., Ph.D. |
author_sort |
Yun Sil Chang |
title |
Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats |
title_short |
Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats |
title_full |
Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats |
title_fullStr |
Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats |
title_full_unstemmed |
Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats |
title_sort |
human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2009-08-01 |
description |
Recent evidence suggests mesenchymal stem cells (MSCs) can downmodulate bleomycin-induced lung injury, and umbilical cord blood (UCB) is a promising source for human MSCs. This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate hyperoxia-induced lung injury in immunocompetent newborn rats. Wild-type Sprague-Dawley rats were randomly exposed to 95% oxygen or air from birth. In the transplantation groups, a single dose of PKH26-labeled human UCB-derived MSCs was administered either intratracheally (2 × 10 6 cells) or intraperitoneally (5 × 10 5 cells) at postnatal day (P) 5. At P14, the harvested lungs were examined for morphometric analyses of alveolarization and TUNEL staining, as well as the myeoloperoxidase activity, the level of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and transforming growth factor (TGF)-β mRNA, α-smooth muscle actin (SMA) protein, and collagen levels. Differentiation of MSCs to the respiratory epithelium was also evaluated both in vitro before transplantation and in vivo after transplantation. Despite one fourth dosage of MSCs, significantly more PKH26-labeled donor cells were recovered with intratracheal administration than with intraperitoneal administration both during normoxia and hyperoxia. The hyperoxia-induced increase in the number of TUNEL-positive cells, myeloperoixdase activity, and the level of IL-6 mRNA were significantly attenuated with both intratracheal and intraperitoneal MSCs transplantation. However, the hyperoxia-induced impaired alveolarization and increased the level of TNF-α and TGF-β mRNA, α-SMA protein, and collagen were significantly attenuated only with intratracheal MSCs transplantation. MSCs differentiated into respiratory epithelium in vitro and a few PKH26-positive donor cells were colocalized with pro surfactant protein C in the damaged lungs. In conclusion, intratracheal transplantation of human UCB-derived MSCs is more effective than intraperitoneal transplantation in attenuating the hyperoxia-induced lung injury in neonatal rats. |
url |
https://doi.org/10.3727/096368909X471189 |
work_keys_str_mv |
AT yunsilchang humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT woniloh humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT soojinchoi humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT dongkyungsung humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT sooyoonkim humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT eunyangchoi humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT saemkang humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT hyejinjin humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT yoonsunyang humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats AT wonsoonparkmdphd humanumbilicalcordbloodderivedmesenchymalstemcellsattenuatehyperoxiainducedlunginjuryinneonatalrats |
_version_ |
1724609639846248448 |