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Open AccessArticle

Thrombin Preconditioning Enhances Therapeutic Efficacy of Human Wharton’s Jelly–Derived Mesenchymal Stem Cells in Severe Neonatal Hypoxic Ischemic Encephalopathy

1
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
2
Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Korea
3
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea
*
Author to whom correspondence should be addressed.
These authors equally contributed to the manuscript.
Int. J. Mol. Sci. 2019, 20(10), 2477; https://doi.org/10.3390/ijms20102477
Received: 21 April 2019 / Revised: 10 May 2019 / Accepted: 17 May 2019 / Published: 20 May 2019
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration)
We investigated whether thrombin preconditioning of human Wharton’s jelly–derived mesenchymal stem cells (MSCs) improves paracrine potency and thus the therapeutic efficacy of naïve MSCs against severe hypoxic ischemic encephalopathy (HIE). Thrombin preconditioning significantly enhances the neuroprotective anti-oxidative, anti-apoptotic, and anti-cytotoxic effects of naïve MSCs against oxygen–glucose deprivation (OGD) of cortical neurons in vitro. Severe HIE was induced in vivo using unilateral carotid artery ligation and hypoxia for 2 h and confirmed using brain magnetic resonance imaging (MRI) involving >40% of ipsilateral hemisphere at postnatal day (P) 7 in newborn rats. Delayed intraventricular transplantation of 1 × 105 thrombin preconditioned but not naïve MSCs at 24 h after hypothermia significantly enhanced observed anti-inflammatory, anti-astroglial, and anti-apoptotic effects and the ensuing brain infarction; behavioral tests, such as cylinder rearing and negative geotaxis tests, were conducted at P42. In summary, thrombin preconditioning of human Wharton’s jelly-derived MSCs significantly boosted the neuroprotective effects of naïve MSCs against OGD in vitro by enhancing their anti-oxidative, anti-apoptotic, and anti-cytotoxic effects, and significantly attenuated the severe HIE-induced brain infarction and improved behavioral function tests in vivo by maximizing their paracrine anti-inflammatory, anti-astroglial, and anti-apoptotic effects. View Full-Text
Keywords: mesenchymal stem cell transplantation; hypoxic-ischemic encephalopathy; translational medical research; infant; newborn; diseases mesenchymal stem cell transplantation; hypoxic-ischemic encephalopathy; translational medical research; infant; newborn; diseases
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Kim, Y.E.; Sung, S.I.; Chang, Y.S.; Ahn, S.Y.; Sung, D.K.; Park, W.S. Thrombin Preconditioning Enhances Therapeutic Efficacy of Human Wharton’s Jelly–Derived Mesenchymal Stem Cells in Severe Neonatal Hypoxic Ischemic Encephalopathy. Int. J. Mol. Sci. 2019, 20, 2477.

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