Articles

Article

Original Article

Exp Neurobiol 2015; 24(2): 146-155

Published online June 30, 2015

https://doi.org/10.5607/en.2015.24.2.146

© The Korean Society for Brain and Neural Sciences

The Effect of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a Collagenase-Induced Intracerebral Hemorrhage Rat Model

Kwanwoo Kim1,2,3, Hyung Woo Park1,2,3, Hyo-Eun Moon1,2,3, Jin Wook Kim1,2,3, Seongtae Bae1,2,3, Jong Wook Chang4, Wonil Oh5, Yoon Sun Yang5 and Sun Ha Paek1,2,3*

1Department of Neurosurgery, 2Cancer Research Institute, 3Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-744, 4Stem Cells & Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 135-710 , 5Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, 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: February 9, 2015; Revised: May 4, 2015; Accepted: May 8, 2015

Abstract

Intracerebral hemorrhage (ICH) is one of the devastating types of stroke. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have potential benefits in recovery from brain damage following ICH. This study aimed to identify the beneficial effects of hUCB-MSCs and investigate whether they have anti-inflammatory effects on the ICH brain via neurotrophic factors or cytokines. hUCB-MSCs were transplanted into a collagenase-induced ICH rat model. At 2, 9, 16, and 30 days after ICH, rotarod and limb placement tests were performed to measure behavioral outcomes. ICH rats were sacrificed to evaluate the volume of lesion using H&E staining. Immunostaining was performed to investigate neurogenesis, angiogenesis, and anti-apoptosis at 4 weeks after transplantation. Inflammatory factors (TNF-α, COX-2, microglia, and neutrophils) were analyzed by immunofluorescence staining, RT-PCR, and Western blot at 3 days after transplantation. hUCB-MSCs were associated with neurological benefits and reduction in lesion volume. The hUCB-MSCs-treated group tended to reveal high levels of neurogenesis, angiogenesis, and anti-apoptosis (significant for angiogenesis). The expression levels of inflammatory factors tended to be reduced in the hUCB-MSCs-treated group compared with the controls. Our study suggests that hUCB-MSCs may improve neurological outcomes and modulate inflammation-associated immune cells and cytokines in ICH-induced inflammatory responses.

Keywords: intracerebral hemorrhage, hUCB-MSCs, neurogenesis, angiogenesis, apoptosis, inflammatory factor