血管紧张素Ⅱ受体在胰腺纤维化大鼠胰腺组织中的表达及其意义

目的动态观察血管紧张素II受体在胰腺纤维化大鼠胰腺组织中的表达并探讨其可能意义。方法采用胰管内注射2%三硝基苯磺酸(TNBS)诱导大鼠胰腺纤维化模型。制模后第3、21、28、35、42、49天分别处死大鼠,每组6只大鼠。对照组仅行剖腹术而未注射TNBS。应用VanGieson(V-G)染色观察胰腺组织纤维化程度。免疫组化和RT-PCR检测胰腺组织AT1蛋白、血管紧张素II受体mRNA和TNF-αmRNA表达。结果模型组大鼠胰腺组织细胞外基质合成较对照组明显增加。胰腺组织TNF-αmRNA表达逐渐增加并于第五周达峰值。AT1、AT2mRNA表达随时间不同呈不同程度的增加,分别于第28天、第35天达到峰值(382%和314%)。与AT1B受体mRNA相比,AT1受体亚型AT1AmRNA表达水平升高更为明显。免疫组化结果提示,模型组大鼠胰腺组织AT1蛋白表达增加并主要分布于纤维化区域。结论血管紧张素II可能通过AT1、AT2介导的途径参与了TNBS诱导的大鼠胰腺组织纤维化形成过程。     

外源性硫化氢抑制TLR2和TLR4表达并减轻大鼠肾脏缺血再灌注损伤

目的观察外源性硫化氢(H₂S)供体硫氢化钠(NaHS)能否抑制Toll样受体2(TLR2)和Toll样受体4(TLR4)表达、减轻大鼠肾脏缺血再灌注损伤(IRI)。 方法24只6~8周龄雄性SD大鼠随机分为3组：假手术(Sham)组、肾脏缺血再灌注(I/R)组、NaHS+I/R组。采用右肾切除联合左肾动脉夹闭45 min后再灌注24 h的方法诱导肾IRI。夹闭左肾动脉前，NaHS+I/R组给予NaHS(300 nmol/min)连续输注10 min，Sham组和I/R组则给予等体积生理盐水。分别留取各组腹主动脉血及肾组织标本。Western印迹法检测肾组织TLR2、TLR4蛋白的表达；免疫组织化学法检测肾组织白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的表达；比色法检测血尿素氮(BUN)、血肌酐(Scr)。HE染色观察肾脏组织学改变；TUNEL法检测肾组织细胞凋亡。 结果与Sham组比较，I/R组的TLR2、TLR4、IL-6、TNF-α表达均增加(P<0.05)，BUN、Scr亦明显升高(P<0.05)，肾小管上皮损伤评分较高(P<0.05)，肾组织凋亡细胞增加(P<0.05)。与I/R组比较，NaHS+I/R组的TLR2、TLR4、IL-6、TNF-α表达均减少(P<0.05)，BUN、Scr亦明显下降(P<0.05)，肾小管上皮损伤评分较低(P<0.05)，肾组织凋亡细胞减少(P<0.05)。 结论外源性H₂S可以抑制TLR2、TLR4途径，减少炎症因子释放及细胞凋亡，减轻大鼠肾脏IRI。     

Toll样受体2/4在糖尿病大鼠肾缺血再灌注损伤时的表达及肾康注射液的保护作用

目的探讨糖尿病(DM)大鼠肾缺血再灌注损伤(IRI)的可能机制及肾康注射液(SKI)的保护作用。 方法采用高糖高脂饮食诱导6周联合小剂量链脲佐菌素的方法建立DM大鼠模型,将造模成功的SD大鼠随机分为糖尿病肾缺血再灌注组(DMIR)、糖尿病肾缺血再灌注SKI治疗组(DMIR＋SKI)、糖尿病假手术组(DMS)和正常对照组(NCS)。DMIR＋SKI组大鼠应用SKI[6.0 g/(kg·d)]干预8周,其它组用等量生理盐水。应用右肾切除联合左肾动脉夹闭45 min后再灌注24 h的方法诱导肾IRI。最后,抽血、留取肾组织。ELISA法检测大鼠血清高迁移率族蛋白(HMGB1)水平;免疫组化方法检测肾组织HMGB1、Toll样受体(TLR)2和TLR4的表达;免疫印迹法和实时定量PCR法检测肾组织TLR2、TLR4、髓样分化因子88 (MyD88),核因子-κBp56 (NF-κBp56)的表达。 结果DMIR组大鼠血清HMGB1水平,肾小管HMGB1、TLR2和TLR4的表达以及肾组织TLR2、TLR4、MyD88和NF-κBp56的蛋白及mRNA水平均明显高于DMS组(P<0.01);经过SKI干预治疗8周,DMIR＋SKI组大鼠的上述指标均明显低于DMIR组(P<0.01)。 结论SKI可通过抑制TLR2/4炎症反应通路,减轻DM大鼠肾IRI炎症反应而起到肾脏保护作用。     

胰腺癌中血管形成因子和细胞粘附分子的表达研究

目的　探讨CD3 4 和血管内皮生长因子 (VEGF)、细胞间粘附分子 (ICAM 1)在胰腺癌(pancreaticadenocarcinoma ,PAC)组织、慢性胰腺炎组织 (chronicpancreatitis ,CP)中的表达及病理意义 ,明确血管形成在胰腺癌演化过程中所起的重要作用。方法　应用免疫组化Envission方法对 2 4例胰腺癌组织、2 4例慢性胰腺炎组织、7例正常胰腺组织 ,进行了CD3 4 、VEGF、ICAM 1的表达情况的检测。对CD3 4 阳性血管进行MVD计数 ,并结合胰腺癌的病理特征进行分析。结果　癌组织 (4 7 2±9 4 )和慢性胰腺炎组织 (4 0 8± 7 93)中微血管密度明显高于对照组 (9 85± 2 86 ) (P <0 0 1)。VEGF在正常胰腺组织中不表达 ,在胰腺癌组织中VEGF主要表达于肿瘤细胞和导管细胞的胞质中 ,在慢性胰腺炎组织中VEGF在叶间及叶内导管细胞均高表达。细胞间粘附分子ICAM 1在正常对照胰腺组织中未见表达 ,仅见于某些内皮细胞着色 ,在胰腺癌组织及慢性胰腺炎组织中 ,除内皮细胞高表达外 ,肿瘤细胞阳性表达亦较高 ,慢性胰腺炎中ICAM 1亦在叶间及小叶内导管细胞中高表达。结论　我们发现微血管形成及其调控因子、细胞粘附分子与慢性胰腺炎、胰腺癌的生物学行为密切相关 ,在胰腺癌的演变中亦起了不可低估的作用 ,抗血管形成治疗无论是对胰腺癌抑     

胰腺内外分泌部微血管内皮细胞不同生物学特性的研究

目的了解正常生理状态、急性水肿性胰腺炎（AEP）胰腺内外分泌部微血管内皮细胞生物学特性的异同。方法应用荧光免疫组织化学染色和共聚焦激光扫描显微镜技术,观察32只正常、AEP Wistar大鼠胰腺内外分泌部微血管内皮细胞VE-cadherin的表达及其变化。结果在胰腺外分泌部,正常鼠微血管内皮细胞的VE-cadherin位于内皮细胞连接处,AEP时微血管内皮细胞VE-cadherin的表达减少且分布异常,并贯穿于整个疾病过程中;而在内分泌部,正常大、中胰岛毛细血管球血管内皮无VE-cadherin阳性染色,小胰岛内有弥漫性染色,其AEP时的表现与生理状态下的比较无明显变化。结论实验结果显示了大、中胰岛及小胰岛血管内皮细胞生物学的特殊性,这种特殊性可能与其相应内环境以及功能的特殊性相关。     

1型血管紧张素Ⅱ受体拮抗剂抑制大鼠胰腺纤维化形成

目的探讨1型血管紧张素Ⅱ受体(AT1)拮抗剂洛沙坦对大鼠实验性胰腺纤维化形成的抑制作用。方法胰管内注射2％三硝基苯磺酸(TNBS)诱导大鼠胰腺纤维化模型。于制模后第2天，治疗组给予洛沙坦(10mg／kg体重)灌胃，每日1次，对照组给予等容积的无菌蒸馏水。于制模后3，7，14，21．28d分别处死两组大鼠(每时点各6只)，并留取血清和胰腺组织。通过HE染色和Van Gieson(V-G)染色观察胰腺组织病理学改变和细胞外基质胶原纤维分布。分别应用放射免疫法和酶动力法测定血清透明质酸(HA)和淀粉酶。胰腺组织AT1受体蛋白和mRNA表达分别采用免疫组化和逆转录-聚合酶链式反应(RT-PCR)方法。结果洛沙坦可抑制TNBS诱导的大鼠胰腺纤维化形成，降低胰腺组织炎症细胞浸润、腺泡细胞坏死及纤维化程度，并且能降低血清HA和淀粉酶水平、下调AT1受体基因和蛋白的表达。结论1型血管紧张素Ⅱ受体拮抗剂对TNBS诱导的大鼠胰腺纤维化形成具有抑制作用，表明肾素-血管紧张素系统(RAS)在慢性胰腺炎胰腺纤维化的发生发展过程中起重要的介导调节作用。     

Toll样受体4在非肥胖型糖尿病鼠胰腺组织的特异性分布表达及其意义

目的 检测Toll样受体4(TLR4)在非肥胖型糖尿病(NOD)鼠胰腺的表达及发病过程中的变化,并探讨其临床意义.方法 利用免疫荧光定位TLR4在胰腺中的表达,采用逆转录-聚合酶链反应( RT-PCR)及Western blot等方法分别从mRNA和蛋白水平探讨其在胰腺中的表达及发病过程中的变化.结果 几乎所有的胰岛β细胞表面均表达TLR4.随着1型糖尿病的进展,胰腺TLR4蛋白相对表达量由1.01 ±0.01上升到3.68±0.10,组间差异有统计学意义(P＜0.01);mRNA相对表达量由1.00±0.02上升到4.76±0.17,组间差异有统计学意义(P＜0.01).结论 随着1型糖尿病的进展,TLR4表达明显增加,其可能通过免疫机制参与了疾病的发生、发展过程.     

TRAIL受体在胰腺癌中的表达及意义

目的:研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)受体在胰腺癌中的表达及意义。方法:应用半定量RT-PCR,检测TRAILR mRNA在胰腺癌组织,正常胰腺组织及胰腺癌细胞系ASPC-1、Can-pan-2中的表达。结果:死亡受体DR4、DR5在所有胰腺癌组织、正常胰腺组织及胰腺癌细胞系中均有表达,诱骗受体DcR1、DcR2在所有正常胰腺组织及细胞系中均有表达。死亡受体DR4、DR5在胰腺癌组织中有较高的表达,而在正常胰腺组织中呈中低水平表达(P<0.01)。胰腺癌细胞系中死亡受体DR4、DR5呈高水平表达,而诱骗受体DcR1、DcR2仅呈中低水平表达。结论:TRAIL受体在胰腺癌普遍表达,并存在受体类型的表达差异;死亡受体在胰腺癌中高表达,可能在TRAIL诱导胰腺癌细胞凋亡的机制中发挥重要的作用。     

肠源性内毒素水平与肝脏Toll样受体4表达在大鼠重症急性胰腺炎肝损伤中变化

目的:探讨肠源性内毒素(ET)与肝脏Toll样受体4(TLR4)表达在重症急性胰腺炎(SAP)肝损伤中的关系.方法:48只Wistar大鼠随机均分为模型组和对照组,模型组用逆行胰胆管注射5％牛磺胆酸钠法制作SAP模型,对照组行假手术.两组分别于术后3,6,12h随机各取8只大鼠,收集胰腺、肝脏组织及外周动脉血,行病理学检查,检测血淀粉酶(AMY),谷丙转氨酶(ALT)和ET水平,并用Western blot法检测肝脏TLR4表达.结果:与对照组比较,模型组胰腺与肝脏病理学评分、血AMY,ALT,ET水平,以及肝组织TLR4蛋白表达水平均明显升高(均P＜0.05),且各指标均随时间不断升高;对照组各指标在各时间点上无明显变化(均P＞0.05);模型组肝脏TLR4蛋白表达水平与血ET呈明显正相关(r=0.863,P＜0.01).结论:SAP时血ET水平升高与肝脏TLR4蛋白的表达上调存在相关性,两者的相互作用可能参与了SAP肝损伤的机制.     

己酮可可碱对大鼠胰腺纤维化及TGF-β1、α-SMA、MMP-1、TIMP-1表达的影响

目的探讨己酮可可碱(PTX)对大鼠胰腺纤维化及TGF-β1、α-SMA、MMP-1、TIMP-1表达的影响。方法通过胰管内注射2%三硝基苯磺酸的方法制备大鼠胰腺纤维化模型。随机分为对照组、模型组、PTX干预组。PTX干预组于术后第2天给予PTX腹腔注射,6mg/(kg·d),4周后收集各组胰腺标本。免疫组化SABC法检测各组胰腺组织中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、基质金属蛋白酶-1(MMP-1)、金属蛋白酶组织抑制物-1(TIMP-1)的表达同时做组织胶原纤维染色。部分胰腺组织液氮冻存,以Westernblot方法检测α-SMA的表达。结果模型组发生胰腺纤维化,PTX干预组有轻度纤维化。PTX干预组α-SMA、TGF-β1、TIMP-1的表达均低于模型组(P<0.01)。MMP-1的表达无明显差异。PTX干预组胶原面积百分比明显低于模型组(P<0.01)。结论PTX抗大鼠胰腺纤维化的作用可能与其降低TGF-β1、α-SMA、TIMP-1表达有关。     

Altered distribution of class I and class II MHC antigens during acute pancreas allograft rejection in the rat

The expression of MHC class I and class II antigens was investigated in a model of acute pancreas allograft rejection in the rat. Pancreaticoduodenal and duct-ligated DA(RT1a)-to-LEW(RT1(1] and LEW(RT1(1]-to-LEW.1U(RT1u) pancreas grafts were compared with normal organs and with LEW(RT1(1] isografts at daily intervals from day 1 to day 10 after transplantation. The results show profound changes of MHC antigen distribution in allografts during the process of rejection. Exocrine acinar cells, being class-I-antigen-negative in the normal pancreas, strongly express these antigens during rejection. Class II antigens, normally not found in pancreatic endothelia or parenchymal cells, appear in duct epithelia, acinar cells, and endothelia of big vessels. Endocrine islet cells and smooth muscle cells stay Ia-negative throughout the rejection process. Focal class I reactivity is also observed in acinar cells of pancreaticoduodenal isografts; but class II antigens are neither seen in parenchymal cells nor in endothelia of any isograft. Thus, in the rat pancreas allograft model, the induction of class II antigens is an early phenomenon characteristic of an ongoing immune response, and it provides a valuable new diagnostic criterion. Antibodies reactive exclusively with donor-haplotype antigens demonstrate an increase in donor-derived class I and class II antigen-positive interstitial cells in addition to parenchymal antigenic changes. A possible effect of the antigenic alteration described on the course of the rejection process is discussed.     

一种研究急性胰腺炎加重病理机理的动物模型

介绍一种急性水肿性胰腺炎（ＡＥＰ）向坏死性胰腺炎（ＡＮＰ）转变的大鼠模型。１０７只ＳＤ大鼠随机分为假手术组、ＡＥＰ组和ＡＮＰ组。ＡＥＰ通过胰管结扎、外分泌刺激诱发。在ＡＥＰ模型基础上静注大剂量Ｄｅｘｔｒａｎ１１０诱发ＡＮＰ。结果显示：血清淀粉酶水平在ＡＥＰ、ＡＮＰ组明显增高，胰腺泡细胞胞浆游离钙离子浓度在ＡＮＰ诱发后持续增高；胰腺出血、实质坏死、钙沉积在ＡＮＰ组常见。超微结构显示ＡＮＰ组胰毛细血管内皮剥脱、坏死。由此表明，胰腺缺血可能通过腺泡细胞钙超负荷的作用促发ＡＥＰ向ＡＮＰ转变。该大鼠模型因临床联系较好、病变渐进，不失为一种从细胞和分子水平研究急性胰腺炎加重病理机理的动物模型     

Immunohistological observations of rat fetal pancreas allografts transplanted into unmodified and cyclosporine-treated recipients

Administration of CsA (15 mg/kg/day) prolonged the survival of DA (RT1a) rat fetal pancreas transplanted to the renal subcapular site of both PVG (RT1c) and Lewis (RT1(1] recipients. Sections of fetal pancreas examined 40 days after transplantation into allogeneic CsA-treated recipients showed growth and development of the fetal pancreas tissue, and the presence of numerous insulin-containing islets. CsA treatment prevented the induction of MHC antigen within allografts. Whereas at day 4, both rejecting and CsA treated grafts showed donor class I MHC expression on duct epithelium and islet cells, only rejecting grafts displayed class I MHC induction on acinar cells. Rejecting grafts showed strong induction of class II MHC antigen expression on duct epithelium from day 4 onward but this was completely prevented by CsA treatment. Islet cells in both rejecting and CsA treated allografts remained class II-negative throughout. CsA also resulted in a reduction in the day 6 cellular infiltrate of allografts (median area leukocyte infiltrate reduced from 43% to 10%) with a marked decrease in the number of MRC OX-8-positive cells. These results show a favorable effect of CsA on rat fetal pancreas allografts with a reduction in MHC antigen expression within the graft and prolonged survival of insulin-rich endocrine tissue.     

Expression of epidermal growth factor receptor after partial pancreatectomy in adult rats: an immunohistochemical study.

The expression and localization of epidermal growth factor (EGF) were investigated immunohistochemically using an anti-EGF receptor antibody in the pancreas of partial pancreatectomized and sham-operated adult rats. In the sham-operated pancreas, immunoreactive products against EGF receptor were only slightly positive in the pancreatic acinar cells. In the partial pancreatectomized pancreas on the fifth day after operation, EGF receptor immunoreactivity was intensely positive in the acinar cells, in some cells lining the intercalated ducts and some basal cells of the acinus, but it was not detected in the pancreas when exogenous EGF was given to the rat after partial pancreatectomy for three days. The present results suggest that EGF receptor is expressed in the regenerating pancreatic tissue, and EGF could be involved in the mechanism of pancreatic regeneration in rats.     

TLR2和TLR4在胰腺癌中的表达及其意义

目的探讨Toll样受体2(TLR2)和Toll样受体4(TLR4)在胰腺癌中的表达及其临床意义。方法采用实时荧光定量PCR检测30例新鲜胰腺癌及相应癌旁组织标本中TLR2及TLR4 mRNA的水平;应用免疫组化检测TLR2和TLR4蛋白在65例胰腺癌及相应38例癌旁组织中的表达;分析它们与临床病理特征的关系。应用Kaplan-Meier法分析TLR2和TLR4蛋白表达对患者生存时间的影响。结果PCR结果显示胰腺癌组织中的TLR2和TLR4 mRNA相对水平分别为0.84±0.17和0.81±0.10,显著高于癌旁组织的0.70±0.13和0.70±0.16(P0.05);免疫组化结果显示TLR2和TLR4在胰腺癌中的表达率分别为63.10%和69.2%,显著高于癌旁组织的34.20%和39.5%(P0.05),TLR2,TLR4的表达与患者性别、年龄、肿瘤部位及分化程度无关,而与肿瘤大小、淋巴结转移、血管侵犯及临床分期有关,上述4指标的分组间差异均有显著性。TLR2或TLR4阴性组患者的生存时间分别为18.4个月和19.4个月,显著长于TLR2或TLR4阳性组(均为12.4个月,P0.05)。结论TLR2及TLR4在胰腺癌中高表达;TLRs信号通路可能促进了胰腺癌的恶性进展。     

急性胰腺炎大鼠TNF-α mRNA、IL-10 mRNA表达和胰腺细胞凋亡的研究

目的 探讨大鼠急性胰腺炎早期胰腺组织中TNF－αmRNA、IL－10mRNA的表达和细胞凋亡的变化规律。方法 以牛磺胆酸钠诱导20只大鼠急性水肿性胰腺炎（AEP）模型,20只急性坏死性胰腺炎（ANP）模型,另取10只正常大鼠作为对照。术后12h各处死10只大鼠,检测血清和胰腺组织中的TNF－α和IL－10水平,分析两者在胰腺组织中的mRNA较录水平,检测胰腺细胞的凋亡率。结果 正常、AEP和ANP组的细胞凋亡率分别为2．98％、17．29％和8．39％。制模后TNF－αm和IL－10增强ANP大鼠TNF－α表达增强。结论 急性胰腺炎大鼠胰腺组织中的TNF－α和IL－10的表达与其在血清和胰腺中的浓度成正比,胰腺本身可能就是产生细胞因子的主要器官。胰腺细胞凋亡率与疾病的严重程度呈负相关,凋亡是对胰腺损伤的良好反应。     

NOB1基因在胰腺癌的表达及其临床意义

目的:探讨NOB1(nin one binding)在胰腺癌组织中的表达情况及与胰腺癌临床病理特征的关系。方法:①SYBR Green实时定量PCR和Western印迹法检测20例胰腺癌及癌旁对照、14例正常胰腺冰冻组织中NOB1基因mRNA及其编码蛋白的表达情况。②免疫组化回顾性检测50例胰腺癌石蜡切片中NOB1蛋白表达情况,并分析其与病人年龄、性别、肿瘤部位、病理分期、淋巴结转移等临床病理特征的相关性。结果:①20例胰腺癌中NOB1基因mRNA表达明显高于癌旁组织,P<0.05;16例(80%)胰腺癌组织中NOB1蛋白明显高于癌旁组织;而14例正常组织中NOB1蛋白阳性率仅14.3%。②免疫组化有34例呈(+++),8例呈(++),4例呈(+),4例呈(-),阳性表达率为84%,且NOB1在多数胰腺癌早期阶段即有强阳性表达。NOB1与肿瘤大小呈正相关(P0.05)。结论:NOB1在胰腺癌组织中高表达,且在较早期胰腺癌中即有强阳性表达,提示可能与胰腺癌发生有密切关系。     

软骨寡聚基质蛋白在慢性胰腺炎损伤中退变腺泡细胞内的表达

目的 研究正常胰腺、慢性胰腺炎与胰腺癌组织中软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)mRNA和蛋白表达水平的差异,揭示COMP在慢性胰腺炎样损伤中的意义。方法 采用Northern印迹法、Western印迹法、原位杂交法与免疫组化方法对14例慢性胰腺炎、14例胰腺癌及15例正常胰腺组织进行分析。结果 在慢性胰腺炎组织中和胰腺癌组织中类似慢性胰腺炎损伤的退变腺泡细胞胞浆内,存在高水平的COMP mRNA信号与免疫反应;而在胰腺癌细胞、正常胰腺组织的导管细胞与胰岛细胞的胞浆内,COMP mRNA信号与免疫反应微弱或缺如。结论 COMP在慢性胰腺炎及胰腺癌中类似慢性胰腺炎损伤的退变腺泡细胞内高表达,可能与慢性胰腺炎中腺泡细胞功能异常有关。     

Acinar cell cystadenoma of the pancreas: a new entity?

This report describes a newly observed cystic lesion of the pancreas showing acinar cell differentiation. The patients affected by this lesion included seven women and three men (age range 16-66 years). In six patients, all of whom were female and all but one of whom suffered from abdominal pain, the cystic lesions (diameters, 4-15 cm) were detected by imaging techniques and subsequently removed. In four patients the cystic lesions were incidental findings. Eight lesions occurred as unifocal, unilocular or multilocular cysts in the head (n = 6) or tail (n = 2) of the pancreas. One lesion was bifocal (head and tail) and another involved the entire pancreas. The cysts were only rarely connected with the pancreatic duct system, but with acinar structures. Their lining cells expressed pancreatic enzymes and lacked any cellular atypia or proliferative activity (Ki67 index <1%). For a follow-up period of 6-84 months all patients remained alive and well. Although a nonneoplastic nature cannot be fully excluded, we propose that this lesion, composed of well-differentiated acinar cells, may represent the benign counterpart of the well-recognized acinar cystadenocarcinoma. We therefore suggest the term acinar cell cystadenoma.     

Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting

During pancreatic development, neogenesis, and regeneration, stem cells might act as a central player to generate endocrine, acinar, and duct cells. Although these cells are well known as pancreatic stem cells (PSCs), indisputable proof of their existence has not been reported. Identification of phenotypic markers for PSCs leads to their prospective isolation and precise characterization to clear whether stem cells exist in the pancreas. By combining flow cytometry and clonal analysis, we show here that a possible pancreatic stem or progenitor cell candidate that resides in the developing and adult mouse pancreas expresses the receptor for the hepatocyte growth factor (HGF) c-Met, but does not express hematopoietic and vascular endothelial antigens such as CD45, TER119, c-Kit, and Flk-1. These cells formed clonal colonies in vitro and differentiated into multiple pancreatic lineage cells from single cells. Some of them could largely expand with self-renewing cell divisions in culture, and, following cell transplantation, they differentiated into pancreatic endocrine and acinar cells in vivo. Furthermore, they produced cells expressing multiple markers of nonpancreatic organs including liver, stomach, and intestine in vitro. Our data strongly suggest that c-Met/HGF signaling plays an important role in stem/progenitor cell function in both developing and adult pancreas. By using this antigen, PSCs could be isolated prospectively, enabling a detailed investigation of stem cell markers and application toward regenerative therapies for diabetes.