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Exp Neurobiol 2017; 26(1): 55-65
Published online February 28, 2017
https://doi.org/10.5607/en.2017.26.1.55
© The Korean Society for Brain and Neural Sciences
Hyung Woo Park1,2,3, Yona Kim1,2,3, Jong Wook Chang5, Yoon Sun Yang4, Wonil Oh4, Jae Min Lee1, Hye Ran Park6, Dong Gyu Kim1,2,3 and Sun Ha Paek1,2,3*
1Department of Neurosurgery, Seoul National University College of Medicine, Seoul 03080, 2Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, 3Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, 4Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 13494, 5Stem Cell & Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, 6Department of Neurosurgery, Soonchunhyang University Hospital, Seoul 31151, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2072-3993, FAX: 82-2-744-8459
e-mail: paeksh@snu.ac.kr
Stem cell therapies are administered during the acute phase of stroke to preserve the penumbral tissues from ischemic injury. However, the effect of repeated cell therapy during the acute phase remains unclear. In this study, we investigated and compared the functional outcome of single (two days post-injury) and repeated (two and nine days post-injury) treatment with human umbilical cord derived mesenchymal stem cells (hUCB-MSCs) after middle cerebral artery occlusion (MCAO). The rotarod and limb placement tests were utilized to investigate functional outcomes, while infarct volume and tissue damage were measured by immunofluorescent staining for neovascularization, neurogenesis, apoptosis, and inflammation in the penumbral zones. We observed notable motor dysfunction and a significant decrease in infarcted brain volume, as well as increases in neurons and vessels in both single and repeated hUCB-MSC treatments compared to the control group. Interestingly, repeated administration of hUCB-MSCs was not found to elicit additional or synergistic improvements over monotherapy. This study suggests that a clearer understanding of the therapeutic window after stroke will facilitate the development of more efficient treatment protocols in the clinical application of stem cell therapy.
Keywords: Human umbilical cord blood mesenchymal stem cell, Ischemia, repeat therapy, Angiogenesis, Neurogenesis