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Intratracheal transplantation of human umbilical cord blood derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats
Authors: Yun Sil Chang, Soo Jin Choi, Dong Kyung Sung, Soo Yoon Kim, Wonil Oh, Yoon Sun Yang, Won Soon Park
Source: Cell Transplantation
Publisher: Cognizant Communication Corporation
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Abstract:
Intratracheal transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuates the hyperoxia-induced neonatal lung injury. The aim of this pre-clinical translation study was to optimize the dose of human UCB-derived MSCs in attenuating hyperoxia-induced lung injury in newborn rats. Newborn Sprague-Dawley rats were randomly exposed to hyperoxia (95% oxygen) or normoxia after birth for 14 days. Three different doses of human UCB-derived MSCs, 5×10³ (HT¹), 5×10⁴ (HT²), and 5×10⁵ (HT³), were delivered intratracheally at postnatal day (P) 5. At P14, lungs were harvested for analyses including morphometry for alveolarization, terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining, myeoloperoxidase activity, mRNA level of tumor necross factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β, human glyceradehyde-3-phosphate dehydrogenase (GAPDH) and p47phox, and collagen levels. Increases in TUNEL positive cells were attenuated in all transplantation groups. However, hyperoxia-induced lung injuries, such as reduced alveolarization, as evidenced by increased mean linear intercept and mean alveolar volume, and increased collagen levels were significantly attenuatedin both HT² and HT³, but not in HT¹, with better attenuation in HT³ than in HT². Dose dependent human GAPDH expression, indicative of the presence of human RNA in lung tissue, was observed only in the transplantation groups, with higher expression in HT³ than in HT², and higher expression in HT² than in HT¹. Hyperoxia-induced inflammatory responses such as increased myeloperoxidase acitivity, mRNA levels of TNF- α, IL-1β, IL-6, and TGF-β of the lung tissue, and up-regulation of both cytosolic and membrane p4phox, indicative of oxidative stress, were significantly attenuated in both HT² and HT³ but not in HT¹. These results demonstrate that intratracheal transplantation of human UCB-derived MSCs with appropriate doses may attenuate hyperoxia-induced lung injury through active involvement of these cells in modulating host inflammatory responses and oxidative stress in neonatal rats.Document Type:
DOI: http://dx.doi.org/10.3727/096368911X565029
Appeared or available online: March 7, 2011
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