Comparison of transplantation modality of human mesenchymal stem cells expressing neurogenin1 in rat middle cerebral artery occlusion model: intra-arterial vs. intra-cerebral

Many clinical and animal studies of mesenchymal stem cells (MSCs) transplantation in ischemic stroke and several neurodegenerative diseases have shown the beneficial effects on functional recovery and inhibition of disease progression. In our previous study, intra-cerebral transplantation of neurogenin1-expressing MSCs (MSCs/Ngn1) in the animal stroke model dramatically improved neurologic deficits compared with the parental MSCs. However, intra-cerebral transplantation is an invasive method and inappropriate modality for human stroke treatment. The aim of this study is to find out the feasibility of intra-arterial transplantation modality compared to intra-cerebral transplantation. Ischemic stroke was induced in male rats by transient occluding the middle cerebral artery for 2 hours. At post-ischemic day 3, MSCs/Ngn1 cells were transplanted via intra-cranial (IC) or intra-arterial (IA) modality. Through 4 weeks, animals were analyzed for changes in the impaired motor functions, the distribution pattern of transplanted cells labeled with superparamagnetic iron oxide (SPIO) labeling, and the serial changes of infarct volume in brain magnetic resonance image (MRI). MRI analysis with the SPIO-labeled cells indicated more even distribution in the animals with IA-MSCs/Ngn1 than the one with IC-MSCs/Ngn1. The animals with IA-MSCs/Ngn1 showed significantly higher recovery in rotarod (p=0.003) and adhesive removal tests (p=0.046) than the animals with IC-MSCs/Ngn1. Although the IC-MSCs/Ngn1 group showed the tendency of reduction of infarct volume compared with IA-NS (normal saline) (p=0.061) and IC-NS (p=0.223) respectively, the IA-MSCs/Ngn1 group showed a significant reduction of the infarct volume compared to the IA-NS (p=0.044) and the tendency of reduction compared to IC-NS (p=0.174). The results indicated that MSCs/Ngn1 exert superior therapeutic effect on behavioral recovery and suppressing ischemic infarcts in the acute ischemic stroke. The results also suggested that intra-arterial transplantation method is not only a safe but also a more effective treatment modality for the treatment of an acute ischemic injury compared to intra-cerebral transplantation.

Author dc:creator

• 신, 동훈

Contributors dc:contributor

• 대학원 의학과
• 104541

• brain ischemia
• mesenchymal stem cells
• modality
• 허혈성 뇌졸중
• 중간엽 줄기 세포
• 투여방법

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000013474
000000013474

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/8628