{"id":{"repo_id":"ajou","oai_identifier":"oai:repository.ajou.ac.kr:201003/1382"},"canonical_url":"https://search.dev.ndltd.org/etd/ajou/oai:repository.ajou.ac.kr:201003/1382","repository":{"repo_id":"ajou","name":"Ajou University","base_url":"http://repository.ajou.ac.kr/oai/request"},"display":{"title":"Neuroprotective Effect of Human Mesenchymal Stem Cell on Dopaminergic Neurons by Anti-inflammatory Action","abstract":"Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). Numerous studies have provided evidence suggesting that neuroinflammation plays a critical role in the pathogenesis of PD. The present study was to evaluate effect of human bone marrow-derived mesenchymal stem cell (hMSCs) on modulation of neuroinflammation. We used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether hMSCs have a protective effect on the dopaminergic system through anti-inflammatory mechanism. hMSCs treatment significantly decreased LPS-induced microglial activation and production of pro-inflammatory cytokines compared to LPS-only treatment group. In co-culture cells of microglia and mesencephalic dopaminergic neurons, hMSCs treatment resulted in a significant reduction of dopaminergic neuronal loss induced by LPS stimulation. In animal study, hMSCs treatment significantly increased survival of TH-ip cells at 7 and 14 days following hMSCS injection, approximately two times more than the LPS-only treatment, which was clearly accompanied by a decrease in activation of microglia. Additionally, cytokine assay in the SN showed that hMSCs treatment significantly down regulated the LPS-induced increase in the expression of TNF-α and iNOS mRNA following LPS stimulation. TNF-α and iNOS release were also significantly decreased in the hMSCs group when compared to the LPS-only treatment group at 4 hr and 3 day following hMSCS injection. The present study demonstrated that MSCs have a neuroprotective effect on dopaminergic neurons via an anti-inflammatory mechanism mediated by the modulation of microglial activation. Along with various trophic effect and transdifferentiational potency, anti-inflammatory mechanism of MSCs could have major therapeutic implication in the treatment of PD.","abstract_html":"Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). Numerous studies have provided evidence suggesting that neuroinflammation plays a critical role in the pathogenesis of PD. The present study was to evaluate effect of human bone marrow-derived mesenchymal stem cell (hMSCs) on modulation of neuroinflammation. We used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether hMSCs have a protective effect on the dopaminergic system through anti-inflammatory mechanism. hMSCs treatment significantly decreased LPS-induced microglial activation and production of pro-inflammatory cytokines compared to LPS-only treatment group. In co-culture cells of microglia and mesencephalic dopaminergic neurons, hMSCs treatment resulted in a significant reduction of dopaminergic neuronal loss induced by LPS stimulation. In animal study, hMSCs treatment significantly increased survival of TH-ip cells at 7 and 14 days following hMSCS injection, approximately two times more than the LPS-only treatment, which was clearly accompanied by a decrease in activation of microglia. Additionally, cytokine assay in the SN showed that hMSCs treatment significantly down regulated the LPS-induced increase in the expression of TNF-α and iNOS mRNA following LPS stimulation. TNF-α and iNOS release were also significantly decreased in the hMSCs group when compared to the LPS-only treatment group at 4 hr and 3 day following hMSCS injection. The present study demonstrated that MSCs have a neuroprotective effect on dopaminergic neurons via an anti-inflammatory mechanism mediated by the modulation of microglial activation. Along with various trophic effect and transdifferentiational potency, anti-inflammatory mechanism of MSCs could have major therapeutic implication in the treatment of PD.","abstract_has_math":false,"creators":["김, 유정"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["이, 필휴","대학원 의학과","200624165"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-31T05:03:12Z","date_published":"2011-01-31T05:03:12Z","updated_at":"2026-07-24T00:51:19Z","subjects":["Human mesenchymal stem cell","anti-inflammation","dopaminergic neurons","mMicroglia","Parkinson’s disease","성체 중간엽 줄기세포","항염증","도파민 신경세포","미세아교세포","파킨슨씨병"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005879","000000005879"],"render_values":[{"text":"http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005879","href":"http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005879","code":true},{"text":"000000005879","href":null,"code":true}]}]},"links":{"outbound_url":"http://repository.ajou.ac.kr/handle/201003/1382","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["이, 필휴","대학원 의학과","200624165","김, 유정"]},{"key":"dc:creator","label":"Author","values":["김, 유정"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-01-31T05:03:12Z","2008"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Theses"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Human mesenchymal stem cell","anti-inflammation","dopaminergic neurons","mMicroglia","Parkinson’s disease","성체 중간엽 줄기세포","항염증","도파민 신경세포","미세아교세포","파킨슨씨병"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://repository.ajou.ac.kr/handle/201003/1382","http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005879","000000005879"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). Numerous studies have provided evidence suggesting that neuroinflammation plays a critical role in the pathogenesis of PD. The present study was to evaluate effect of human bone marrow-derived mesenchymal stem cell (hMSCs) on modulation of neuroinflammation. We used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether hMSCs have a protective effect on the dopaminergic system through anti-inflammatory mechanism. hMSCs treatment significantly decreased LPS-induced microglial activation and production of pro-inflammatory cytokines compared to LPS-only treatment group. In co-culture cells of microglia and mesencephalic dopaminergic neurons, hMSCs treatment resulted in a significant reduction of dopaminergic neuronal loss induced by LPS stimulation. In animal study, hMSCs treatment significantly increased survival of TH-ip cells at 7 and 14 days following hMSCS injection, approximately two times more than the LPS-only treatment, which was clearly accompanied by a decrease in activation of microglia. Additionally, cytokine assay in the SN showed that hMSCs treatment significantly down regulated the LPS-induced increase in the expression of TNF-α and iNOS mRNA following LPS stimulation. TNF-α and iNOS release were also significantly decreased in the hMSCs group when compared to the LPS-only treatment group at 4 hr and 3 day following hMSCS injection. The present study demonstrated that MSCs have a neuroprotective effect on dopaminergic neurons via an anti-inflammatory mechanism mediated by the modulation of microglial activation. Along with various trophic effect and transdifferentiational potency, anti-inflammatory mechanism of MSCs could have major therapeutic implication in the treatment of PD.","파킨슨 씨 병은 흑색질 안에 도파민 신경세포의 감소가 원인이 되는 퇴행성 뇌질환이다. 이미 여러 연구에서 신경염증이 파킨슨 씨 병의 발병에 중요한 역할을 함이 증명되었다. 현 우리 실험에서는 성체 중간엽 세포가 신경염증을 완화하는 효과를 확인하였다. 우리는 lipopolysaccharide (LPS)로 실헌 동물 모델과 세포 모델을 만들어 염증을 유도한 후 성체 중간엽 줄기세포가 항염증 메커니즘을 통하여 도파민 신경세포를 보호하는 효과를 갖는지 확인하였다. 성체 중간엽 줄기세포를 처리하였을 때 LPS만 처리한 개체군과 비교하여 LPS에 의해 유도된 전구염증 사이토카인의 증가와 미세아교세포의 활성이 유의미하게 감소함을 알 수 있었다. 또한 미세아교세포와 중뇌 도파민 신경세포의 co-culture system에서 성체 중간엽 줄기세포를 처리한 경우 LPS로 인한 도파민 신경세포의 감소가 현저히 줄어듦을 확인하였다. 그리고 동물 실험을 통하여 성체 중간엽 줄기세포를 주입하였을 때 성체 중간엽 줄기세포를 주입한지 7, 14일이 지난 후 TH-immunopositive (TH-ip)를 표현하는 세포가 증가함을 확인하였으며 이는 LPS 개체군에 비하여 그 양이 대략 두 배 이상이었고 흑색질에서 미세아교세포의 활성의 감소도 수반하였다. 그리고 흑색질 안의 사이토카인 정량 실험 결과, 성체 중간엽 줄기세포를 주입한 개체군은 LPS에 의해 증가된 TNF-α와 iNOS mRNA의 발현을 조절억제 되었고, 성체 중간엽 줄기세포가 주입된지 4시간과 3일 후의 개체군에서 TNF-α와 iNOS의 발현 역시 LPS만 투여된 개체군에 비교하여 유의미하게 감소됨을 관찰하였다. 본 연구는 성체 중간엽 줄기세포가 항염증 메커니즘을 통하여 미세아교세포의 활성을 조절함으로 도파민 신경세포를 보호하는 것을 확인하였고, 이는 다양한 trophic effect와 transdifferentiation 가능성과 함께 성체 중간엽 줄기세포의 항염증 메커니즘이 파킨슨 씨 병의 치료에 주요하게 사용될 수 있음을 시사한다.","\"ABSTRACT = ⅰ TABLE OF CONTENTS = ⅱ LIST OF FIGURES = ⅳ Ⅰ. INTRODUCTION = 1 Ⅱ. MATERIALS AND METHODS = 3 A. MATERIALS = 3 B. METHODS = 4 1. Isolation of hMSCs and culture maintenance = 4 2. Co-culture of LPS treated enriched-microglia or neuron-glia culture with transwell hMSCs insert = 4 3. Microglia enriched cultures = 5 4. Co-cultures of microglia and mesencephalic neuron cultures = 5 5. Determination of NO release = 6 6. Animals study = 6 7. Reverse transcription PCR (RT-PCR) = 7 8. Quantification of TNF-α release = 8 9. Tissue preparation = 8 10. Immunocytochemistry and immunohistochemistry = 9 11. Stereological cell counts = 9 12. Statistical analysis = 10 Ⅲ. RESULTS = 11 1. hMSCs decreased LPS-induced microglial activation = 11 2. hMSCs treatment significantly decreased LPS-induced expression of inflammatory cytokine = 11 3. hMSCs treatment significantly reduced dopaminergic neuronal death induced by LPS stimulation in mesencephalic tissue and microglia co-cultured system = 12 4. hMSCs treatment significantly decreased dopaminergic neuronal loss and microglia activation induced by LPS stimulation in the SN = 12 5. hMSCs reduced the protein expression of TNF-α release induced by LPS stimulation = 13 Ⅳ. DISCUSSION = 23 REFERENCES = 27 국문요약 = 33\"","Master"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Neuroprotective Effect of Human Mesenchymal Stem Cell on Dopaminergic Neurons by Anti-inflammatory Action","성체 중간엽 줄기세포의 항염증 작용을 통한 도파민 신경세포의 보호 효과"]}]}],"canonical_facts":{"dc:contributor":["이, 필휴","대학원 의학과","200624165","김, 유정"],"dc:creator":["김, 유정"],"dc:date":["2011-01-31T05:03:12Z","2008"],"dc:description":["Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). Numerous studies have provided evidence suggesting that neuroinflammation plays a critical role in the pathogenesis of PD. The present study was to evaluate effect of human bone marrow-derived mesenchymal stem cell (hMSCs) on modulation of neuroinflammation. We used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether hMSCs have a protective effect on the dopaminergic system through anti-inflammatory mechanism. hMSCs treatment significantly decreased LPS-induced microglial activation and production of pro-inflammatory cytokines compared to LPS-only treatment group. In co-culture cells of microglia and mesencephalic dopaminergic neurons, hMSCs treatment resulted in a significant reduction of dopaminergic neuronal loss induced by LPS stimulation. In animal study, hMSCs treatment significantly increased survival of TH-ip cells at 7 and 14 days following hMSCS injection, approximately two times more than the LPS-only treatment, which was clearly accompanied by a decrease in activation of microglia. Additionally, cytokine assay in the SN showed that hMSCs treatment significantly down regulated the LPS-induced increase in the expression of TNF-α and iNOS mRNA following LPS stimulation. TNF-α and iNOS release were also significantly decreased in the hMSCs group when compared to the LPS-only treatment group at 4 hr and 3 day following hMSCS injection. The present study demonstrated that MSCs have a neuroprotective effect on dopaminergic neurons via an anti-inflammatory mechanism mediated by the modulation of microglial activation. Along with various trophic effect and transdifferentiational potency, anti-inflammatory mechanism of MSCs could have major therapeutic implication in the treatment of PD.","파킨슨 씨 병은 흑색질 안에 도파민 신경세포의 감소가 원인이 되는 퇴행성 뇌질환이다. 이미 여러 연구에서 신경염증이 파킨슨 씨 병의 발병에 중요한 역할을 함이 증명되었다. 현 우리 실험에서는 성체 중간엽 세포가 신경염증을 완화하는 효과를 확인하였다. 우리는 lipopolysaccharide (LPS)로 실헌 동물 모델과 세포 모델을 만들어 염증을 유도한 후 성체 중간엽 줄기세포가 항염증 메커니즘을 통하여 도파민 신경세포를 보호하는 효과를 갖는지 확인하였다. 성체 중간엽 줄기세포를 처리하였을 때 LPS만 처리한 개체군과 비교하여 LPS에 의해 유도된 전구염증 사이토카인의 증가와 미세아교세포의 활성이 유의미하게 감소함을 알 수 있었다. 또한 미세아교세포와 중뇌 도파민 신경세포의 co-culture system에서 성체 중간엽 줄기세포를 처리한 경우 LPS로 인한 도파민 신경세포의 감소가 현저히 줄어듦을 확인하였다. 그리고 동물 실험을 통하여 성체 중간엽 줄기세포를 주입하였을 때 성체 중간엽 줄기세포를 주입한지 7, 14일이 지난 후 TH-immunopositive (TH-ip)를 표현하는 세포가 증가함을 확인하였으며 이는 LPS 개체군에 비하여 그 양이 대략 두 배 이상이었고 흑색질에서 미세아교세포의 활성의 감소도 수반하였다. 그리고 흑색질 안의 사이토카인 정량 실험 결과, 성체 중간엽 줄기세포를 주입한 개체군은 LPS에 의해 증가된 TNF-α와 iNOS mRNA의 발현을 조절억제 되었고, 성체 중간엽 줄기세포가 주입된지 4시간과 3일 후의 개체군에서 TNF-α와 iNOS의 발현 역시 LPS만 투여된 개체군에 비교하여 유의미하게 감소됨을 관찰하였다. 본 연구는 성체 중간엽 줄기세포가 항염증 메커니즘을 통하여 미세아교세포의 활성을 조절함으로 도파민 신경세포를 보호하는 것을 확인하였고, 이는 다양한 trophic effect와 transdifferentiation 가능성과 함께 성체 중간엽 줄기세포의 항염증 메커니즘이 파킨슨 씨 병의 치료에 주요하게 사용될 수 있음을 시사한다.","\"ABSTRACT = ⅰ TABLE OF CONTENTS = ⅱ LIST OF FIGURES = ⅳ Ⅰ. INTRODUCTION = 1 Ⅱ. MATERIALS AND METHODS = 3 A. MATERIALS = 3 B. METHODS = 4 1. Isolation of hMSCs and culture maintenance = 4 2. Co-culture of LPS treated enriched-microglia or neuron-glia culture with transwell hMSCs insert = 4 3. Microglia enriched cultures = 5 4. Co-cultures of microglia and mesencephalic neuron cultures = 5 5. Determination of NO release = 6 6. Animals study = 6 7. Reverse transcription PCR (RT-PCR) = 7 8. Quantification of TNF-α release = 8 9. Tissue preparation = 8 10. Immunocytochemistry and immunohistochemistry = 9 11. Stereological cell counts = 9 12. Statistical analysis = 10 Ⅲ. RESULTS = 11 1. hMSCs decreased LPS-induced microglial activation = 11 2. hMSCs treatment significantly decreased LPS-induced expression of inflammatory cytokine = 11 3. hMSCs treatment significantly reduced dopaminergic neuronal death induced by LPS stimulation in mesencephalic tissue and microglia co-cultured system = 12 4. hMSCs treatment significantly decreased dopaminergic neuronal loss and microglia activation induced by LPS stimulation in the SN = 12 5. hMSCs reduced the protein expression of TNF-α release induced by LPS stimulation = 13 Ⅳ. DISCUSSION = 23 REFERENCES = 27 국문요약 = 33\"","Master"],"dc:format":["application/pdf"],"dc:identifier":["http://repository.ajou.ac.kr/handle/201003/1382","http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005879","000000005879"],"dc:language":["en"],"dc:subject":["Human mesenchymal stem cell","anti-inflammation","dopaminergic neurons","mMicroglia","Parkinson’s disease","성체 중간엽 줄기세포","항염증","도파민 신경세포","미세아교세포","파킨슨씨병"],"dc:title":["Neuroprotective Effect of Human Mesenchymal Stem Cell on Dopaminergic Neurons by Anti-inflammatory Action","성체 중간엽 줄기세포의 항염증 작용을 통한 도파민 신경세포의 보호 효과"],"dc:type":["Thesis","Theses"]},"updated_at":"2026-07-24T00:51:19Z"}