Article

Original Article

Exp Neurobiol 2015; 24(4): 358-365

Published online December 30, 2015

https://doi.org/10.5607/en.2015.24.4.358

© The Korean Society for Brain and Neural Sciences

The Effect of Donor-Dependent Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells following Focal Cerebral Ischemia in Rats

Hyung Woo Park1,2,3, Jong Wook Chang5, Yoon Sun Yang4, Wonil Oh4, Jae Ha Hwang1,2,3, Dong Gyu Kim1,2,3 and Sun Ha Paek1,2,3*

1Department of Neurosurgery, 2Cancer Research Institute, 3Ischemic/Hypoxic Disease Institute,
Seoul National University College of Medicine, Seoul 03082,
4Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 13494, 5Stem Cell & Regenerative Medicine Center,
Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, 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

Received: August 21, 2015; Revised: October 27, 2015; Accepted: October 29, 2015

Abstract

Stroke is an ischemic disease caused by clotted vessel-induced cell damage. It is characterized by high morbidity and mortality and is typically treated with a tissue plasminogen activator (tPA). However, this therapy is limited by temporal constraints. Recently, several studies have focused on cell therapy as an alternative treatment. Most researches have used fixed donor cell administration, and hence, the effect of donor-dependent cell administration is unknown. In this study, we administered 3 types of donor-derived human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in the ischemic boundary zone of the ischemic stroke rat model. We then performed functional and pathological characterization using rotarod, the limb placement test, and immunofluorescent staining. We observed a significant decrease in neuron number, and notable stroke-like motor dysfunction, as assessed by the rotarod test (~40% decrease in time) and the limb placement test (4.5 point increase) in control rats with ischemic stroke. The neurobehavioral performance of the rats with ischemic stroke that were treated with hUCB-MSCs was significantly better than that of rats in the vehicle-injected control group. Regardless of which donor cells were used, hUCB-MSC transplantation resulted in an accumulation of neuronal progenitor cells, and angiogenic and tissue repair factors in the ischemic boundary zone. The neurogenic and angiogenic profiles of the 3 types of hUCB-MSCs were very similar. Our results suggest that intraparenchymal administration of hUCB-MSCs results in significant therapeutic effects in the ischemic brain regardless of the type of donor.

Keywords: hUCB-MSCs, Ischemia, Angiogenesis, Neurogenesis, Donor-dependent cell therapy