Mesenchymal Stem Cells Therapy in Progressive Rat Model of Parkinson's Disease

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). In present study, we investigated the effect of human mesenchymal stem cells (hMSCs) therapy in vitro and progressive SD rat model of PD using MG-132, proteasome inhibitor. Immunocytochemical analyses in primary mesencephalic culture revealed that hMSC treatment increased dopaminergic neuronal survival compared to dopaminergic neuronal death in MG-132 treatment. Additionally, hMSCs treatment showed that there was a significant reduction of increased caspase 3 activity following MG-132 treatment. In Rats received systemic injection of MG-132, quantification of the extent of neuronal loss assessed by stereological analysis revealed that TH+ positive cell loss was 23% ± 7.2% ( p <0.05, n=5 per group) at 8 weeks, 70 ± 9.5 at 10 weeks (p <0.01, n=5 per group), and 92 ± 7.2 at 13 weeks (p <0.01, n=5 per group). hMSCs treatment dramatically reduced a decline in the number of TH-immunoreactive cells in the SN of MG-132-treated rats, showing approximately 50% increase of survival in TH-immunoreactive cells in the SN compared to only MG-132-treated group (p<0.05). Additionally, hMSC treatment in MG-132-treated rats revealed that increased OX-42 immunoreactivity induced by MG-132 was markedly decreased. Histological analysis showed that the number of NuMA-positive cells was 1.7% of total injected hMSCs and the number of cell double-stained with NuMA and TH was 35.7 % of NuMA-positive cells. In addition, these cells seem to have a functional characteristic of neurons, demonstrating triple-stained with NuMA, TH, and synaptophysin. Behavioral analysis revealed that hMSC treatment in MG-132-treated rats had a tendency of increase in mean stay time on the rod at a 25 rpm (p<0.1). In conclusion, we have shown that hMSC treatment have a protective effect of dopaminergic neuronal cell death induced by MG-132 in vitro and in vivo. Complex mechanisms mediated by trophic effect of hMSCs and differentiation of hMSCs into functional TH-positive neurons may work in the neuroprotective process of hMSCs. In addition, neuroprotective strategies of hMSCs in this study may be clinically applicable.

Author dc:creator

• 박, 현정

Contributors dc:contributor

• 이, 필휴
• 대학원 의학과
• 200524178

• 파킨슨 씨 병
• MG-132
• 단백질 분해 억제제
• human mesenchymal stem cells
• substantia nigra

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000002291
000000002291

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1316