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Kim, Seong Gi
뇌과학 이미징 연구단
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Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats

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Title
Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats
Author(s)
Jung, So Yeon; Kim, Young Eun; Park, Won Soon; Ahn, So Yoon; Sung, Dong Kyung; Sung, Se In; Joo, Kyeung Min; Seong Gi Kim; Chang, Yun Sil
Publication Date
2022-04
Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, no.8
Publisher
MDPI
Abstract
Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced efficacy is necessary. This study investigated whether thrombin preconditioning improves the therapeutic efficacy of human Wharton's jelly-derived MSC transplantation for severe neonatal IVH, using a rat model. Severe neonatal IVH was induced by injecting 150 mu L blood into each lateral ventricle on postnatal day (P) 4 in Sprague-Dawley rats. After 2 days (P6), naive MSCs or thrombin-preconditioned MSCs (1 x 10(5)/10 mu L) were transplanted intraventricularly. After behavioral tests, brain tissues and cerebrospinal fluid of P35 rats were obtained for histological and biochemical analyses, respectively. Thrombin-preconditioned MSC transplantation significantly reduced IVH-induced ventricular dilatation on in vivo magnetic resonance imaging, which was coincident with attenuations of reactive gliosis, cell death, and the number of activated microglia and levels of inflammatory cytokines after IVH induction, compared to naive MSC transplantation. In the behavioral tests, the sensorimotor and memory functions significantly improved after transplantation of thrombin-preconditioned MSCs, compared to naive MSCs. Overall, thrombin preconditioning significantly improves the therapeutic potential and more effectively attenuates brain injury, including progressive ventricular dilatation, gliosis, cell death, inflammation, and neurobehavioral functional impairment, in newborn rats with induced severe IVH than does naive MSC transplantation.
URI
https://pr.ibs.re.kr/handle/8788114/11418
DOI
10.3390/ijms23084447
ISSN
1661-6596
Appears in Collections:
Center for Neuroscience Imaging Research (뇌과학 이미징 연구단) > 1. Journal Papers (저널논문)
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