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Anti-inflammatory effects of canine adipose-derived mesenchymal stem cells in a rat model of severe acute pancreatitis
급성췌장염랫드모델에서 개의 지방유래 중간엽 줄기세포의 항염증효과

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dc.contributor.advisor윤화영-
dc.contributor.author김현욱-
dc.date.accessioned2017-07-13T16:46:30Z-
dc.date.available2017-07-13T16:46:30Z-
dc.date.issued2017-02-
dc.identifier.other000000142702-
dc.identifier.urihttps://hdl.handle.net/10371/120262-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 수의학과, 2017. 2. 윤화영.-
dc.description.abstract중증 급성 췌장염은 개들의 개들의 전신 합병증과 높은 사망률과 관련이 있다 . 간엽 줄기 세포 는 몇 가지 염증 모델에서 치료 가능성에 대한 연구가 있었다 . 본 연구에서는 3% sodium sodium taurocholate taurocholate taurocholate solution solution 을 췌관으로 역행 주사하여 유도 한 중증 급성 췌장염의 췌장염의 랫드 모델에서 개의 지방유래 중간엽 줄기세포(cATMSC) (cATMSC)(cATMSC) (cATMSC)(cATMSC)의 효과를 조사 하였다 . dioctadecyl-3,3,3-tetramethylindocarocyanine percholrate (1 x 10 7 cellscellscells cells / kg)로 표지 된 cATMSC를 랫트에 전신 투여하고 조직 병리학적, 정량적 실시간 PCR 및 면역 세포 화학적 분석을 위해 3 일 후 췌장 조직을 채취 하였다. 대조군에 비해 중증 급성 췌장염을 유발한 랫트의 췌장에서 cATMSCs가 더 많이 검출되었다. cATMSC 주입은 췌장 부종, 염증 세포 침윤 및 선세포 괴사를 감소 시켰고 전 염증성 사이토 카인 TNF-α, Interleukin(IL) -1β, -6, -12, -17 및 -23의 췌장 발현을 감소시켰다. 또한 Interferon-γ를 억제하는 반면, 중증 급성 췌장염 랫드에서 항 염증성 사이토 카인 IL-4 및 IL-10의 발현을 촉진했다. 더욱이, cATMSCs는 손상된 췌장에서 분화 3-positive T cell의 클러스터 수를 감소 시켰고, Forkhead box P3-positve T cell의 수를 증가시켰다. 이러한 결과는 cATMSC가 개에서의 중증 급성 췌장염 치료를위한 세포 기반 치료 전략으로 효과적 일 수 있음을 나타낸다.-
dc.description.abstractSevere acute pancreatitis (SAP) is associated with systemic complications and high mortality rate in dogs. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential in several inflammation models. The present study investigated the effects of canine adipose tissue-derived (cAT)MSCs in a rat model of SAP induced by retrograde injection of 3% sodium taurocholate solution into the pancreatic duct. cATMSCs labeled with dioctadecyl-3,3,3-tetramethylindo-carbocyanine perchlorate (1 × 10 7 cells/kg) were systemically administered to rats and pancreatic tissue was collected 3 days later for histopathological, quantitative real-time PCR, and immunocytochemical analyses. Greater numbers of infused cATMSCs were detected in the pancreas of SAP as compared to sham-operated rats. cATMSC infusion reduced pancreatic edema, inflammatory cell infiltration, and acinar cell necrosis, and decreased pancreatic expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, -6, -12, -17, and -23 and interferon-γ, while stimulating expression of the anti-inflammatory cytokines IL-4 and IL-10 in SAP rats. Moreover, cATMSCs decreased the number of cluster of differentiation 3-positive T cells and increased that of Forkhead box P3-positive T cells in the injured pancreas. These results indicate that cATMSCs can be effective as a cell-based therapeutic strategy for treatment of SAP in dogs.-
dc.description.tableofcontents1. Literature Review 1
1.1 Severe acute pancreatitis and their treatment 1
1.2 Mesenchymal stem cells (MSC) 2
1.3 The anti-inflammatory effect of MSCs 3
1.4 Therapeutic potential of MSCs in severe acute pancreatitis 9
2. Isolation of canine mesenchymal stem cell from adipose tissues 10
2.1. Introduction 10
2.2. Materials and methods 11
2.2.1 Adipose tissue isolation 11
2.2.2 Cell culture 11
2.2.3 Flow cytometery 11
2.2.4 Differentiation 13
2.3. Results 13
2.3.1 Characterization of cATMSCs 13
2.4.Discussion 14
3. Therapeutic effects of canine ATMSCs on SAP in the rat model 16
3.1. Introduction 16
3.2. Material and methods 17
3.2.1 Animal experimental and cell transplantation 17
3.2.2 Histological analysis 19
3.2.3 Measurement of serum amylase, lipase, and inflammatory cytokine level 19
3.2.4 RNA extraction and quantitative real-time PCR 20
3.2.5 Canine peripheral blood mononuclear cell (cPBMC) isolation 20
3.2.6 Rat splenocyte isolation 21
3.2.7 Mixed lymphocyte reaction (MLR) 21
3.2.8 Immunocytochemistry 22
3.2.9 Statistical analysis 22
3.3. Results 23
3.3.1 Histological analysis and assessment of pancreatic markers after cATMSCs infusion 23
3.3.2 Detection of systemically infused cATMSCs in rat pancreas 23
3.3.3 Effect of cATMSCs on inflammatory response 24
3.3.4 T cell regulation by cATMSCs 24
3.4. Discussion 25
4. General conclusion 33
5. References 34
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dc.formatapplication/pdf-
dc.format.extent1290092 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectSevere Acute Pancreatitis-
dc.subject.ddc636-
dc.titleAnti-inflammatory effects of canine adipose-derived mesenchymal stem cells in a rat model of severe acute pancreatitis-
dc.title.alternative급성췌장염랫드모델에서 개의 지방유래 중간엽 줄기세포의 항염증효과-
dc.typeThesis-
dc.contributor.AlternativeAuthorKIM HYUN WOOK-
dc.description.degreeDoctor-
dc.citation.pages44-
dc.contributor.affiliation수의과대학 수의학과-
dc.date.awarded2017-02-
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Theses (Ph.D. / Sc.D._수의학과)
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