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Int. J. Mol. Sci. 2016, 17(9), 1550; doi:10.3390/ijms17091550

Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

1
Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
2
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
3
Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul 03722, Korea
4
Yonsei Stem Cell Research Center, Avison Biomedical Research Center, Seoul 03722, Korea
5
Graduate Program of Nano Science and Technology, Yonsei University, Seoul 03722, Korea
6
Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea
7
Department of Rehabilitation Medicine, Hallym University Burn Institute, Burn Center, Hangang Sacred Heart Hospital, Seoul 03722, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Maurizio Muraca
Received: 1 July 2016 / Revised: 25 August 2016 / Accepted: 5 September 2016 / Published: 14 September 2016
(This article belongs to the Special Issue Advances in Cell Transplantation)
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Abstract

Transplantation of mesenchymal stem cells (MSCs) has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE) in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS)-control (CON), PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes. View Full-Text
Keywords: hypoxic-ischemic brain injury; mesenchymal stem cells; enriched environment; angiogenesis; astrocytes hypoxic-ischemic brain injury; mesenchymal stem cells; enriched environment; angiogenesis; astrocytes
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MDPI and ACS Style

Cho, S.-R.; Suh, H.; Yu, J.H.; Kim, H.H.; Seo, J.H.; Seo, C.H. Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury. Int. J. Mol. Sci. 2016, 17, 1550.

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