Young Eun Kim1, Won Soon Park1,2,3, Dong Kyung Sung2,3, So Yoon Ahn2,3, Se In Sung2, Hye Soo Yoo2, Yun Sil Chang1,2,3. 1. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea. 2. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 3. Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.
Abstract
BACKGROUND: Bronchopulmonary dysplasia is an independent risk factor for adverse neurodevelopmental outcomes in premature infants. We investigated whether attenuation of hyperoxic lung injury with intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells (MSCs) could simultaneously mitigate brain damage in neonatal rats. METHODS: Newborn Sprague-Dawley rats were exposed to hyperoxia or normoxia conditions for 14 d. MSCs (5 × 10(5) cells) were transplanted intratracheally at postnatal day (P) 5. At P14, lungs and brains were harvested for histological and biochemical analyses. RESULTS: Hyperoxic lung injuries, such as impaired alveolarization evident from increased mean linear intercept (MLI) and elevated inflammatory cytokine levels were significantly alleviated with MSC transplantation. Hyperoxia decreased brain weight, increased brain cell death, and induced hypomyelination. MSC transplantation significantly ameliorated hyperoxia-induced increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the dentate gyrus and reduced myelin basic protein. In correlation analyses, brain weight and myelin basic protein (MBP) were significantly inversely correlated with lung MLI and inflammatory cytokines, while TUNEL-positive brain cell number showed a significant positive correlation with lung MLI. CONCLUSION: Despite no significant improvement in short-term neurofunctional outcome, intratracheal transplantation of MSCs simultaneously attenuated hyperoxic lung and brain injuries in neonatal rats, with the extent of such attenuation being closely linked in the two tissues.
BACKGROUND:Bronchopulmonary dysplasia is an independent risk factor for adverse neurodevelopmental outcomes in premature infants. We investigated whether attenuation of hyperoxic lung injury with intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells (MSCs) could simultaneously mitigate brain damage in neonatal rats. METHODS: Newborn Sprague-Dawley rats were exposed to hyperoxia or normoxia conditions for 14 d. MSCs (5 × 10(5) cells) were transplanted intratracheally at postnatal day (P) 5. At P14, lungs and brains were harvested for histological and biochemical analyses. RESULTS:Hyperoxic lung injuries, such as impaired alveolarization evident from increased mean linear intercept (MLI) and elevated inflammatory cytokine levels were significantly alleviated with MSC transplantation. Hyperoxia decreased brain weight, increased brain cell death, and induced hypomyelination. MSC transplantation significantly ameliorated hyperoxia-induced increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the dentate gyrus and reduced myelin basic protein. In correlation analyses, brain weight and myelin basic protein (MBP) were significantly inversely correlated with lung MLI and inflammatory cytokines, while TUNEL-positive brain cell number showed a significant positive correlation with lung MLI. CONCLUSION: Despite no significant improvement in short-term neurofunctional outcome, intratracheal transplantation of MSCs simultaneously attenuated hyperoxic lung and brain injuries in neonatal rats, with the extent of such attenuation being closely linked in the two tissues.
Authors: Mustafa Anjari; Serena J Counsell; Latha Srinivasan; Joanna M Allsop; Joseph V Hajnal; Mary A Rutherford; A David Edwards Journal: Pediatrics Date: 2009-07 Impact factor: 7.124
Authors: Yun Sil Chang; So Yoon Ahn; Hong Bae Jeon; Dong Kyung Sung; Eun Sun Kim; Se In Sung; Hye Soo Yoo; Soo Jin Choi; Won Il Oh; Won Soon Park Journal: Am J Respir Cell Mol Biol Date: 2014-09 Impact factor: 6.914
Authors: So Yoon Ahn; Yun Sil Chang; Dong Kyung Sung; Se In Sung; Hye Soo Yoo; Geun Ho Im; Soo Jin Choi; Won Soon Park Journal: PLoS One Date: 2015-07-24 Impact factor: 3.240
Authors: Yun Sil Chang; Soo Jin Choi; So Yoon Ahn; Dong Kyung Sung; Se In Sung; Hye Soo Yoo; Won Il Oh; Won Soon Park Journal: PLoS One Date: 2013-01-21 Impact factor: 3.240
Authors: Luis Arruza; Maria Ruth Pazos; Nagat Mohammed; Natalia Escribano; Hector Lafuente; Martín Santos; Francisco J Alvarez-Díaz; William Hind; Jose Martínez-Orgado Journal: Pediatr Res Date: 2017-05-03 Impact factor: 3.756
Authors: Sajit Augustine; Wei Cheng; Marc T Avey; Monica L Chan; Srinivasa Murthy Chitra Lingappa; Brian Hutton; Bernard Thébaud Journal: Stem Cells Transl Med Date: 2019-11-20 Impact factor: 6.940