骨髓间充质干细胞移植修复损伤大鼠胃黏膜的实验研究
|
摘要
研究背景:
骨髓间充质干细胞(Bone marrow mesenchymal stem cells,BMMSCs)是骨髓中一种非造血类的干细胞。近些年来的研究发现,间充质干细胞(mesenchymal stem cells,MSCs)由于具有多向分化潜能、低免疫原性和易于体外扩增等特点,受到医学应用领域的广泛关注。应用骨髓MSCs移植进行细胞替代治疗,目前已被广泛应用于缺血或损伤性疾病以及器官移植、抗免疫排斥反应等研究领域,并取得了初步效果。因此,干细胞替代治疗有望成为临床上一种新的治疗手段。
目的:体外培养和扩增的骨髓间充质干细胞对损伤胃黏膜的修复作用及其机制研究。
方法:1、分别采用全骨髓贴壁法和密度梯度离心法体外培养和扩增Wistar大鼠的骨髓MSCs,应用MTT方法比较两种方法下骨髓MSCs的自然生长曲线,流式细胞仪检测骨髓MSCs表面标志物,对培养、纯化的骨髓MSCs进行鉴定。2、以活体染料羟基荧光素乙酰乙酸(5,6-carboxyfluoresceindiacetate succinimidyl ester,CFDA SE)体外标记骨髓MSCs,荧光显微镜下、488nm波长激发光下观察标记后细胞的生长状态;制备大鼠胃黏膜损伤组织冰冻切片,荧光显微镜下观察移植骨髓MSCs的定植。利用大鼠性别决定基因SRY对移植细胞进行体内示踪。3、选择健康成年Wistar大鼠(体重200g-250g)54只,8周龄,雌雄各半,随机分为对照组和实验组,实验组又分为移植组和非移植组,每组18只。实验组用消炎痛30mg/Kg皮下注射,造成胃损伤模型。造模后2h,移植组大鼠经尾静脉注射骨髓MSCs(1×10~7/只);非移植组大鼠经尾静脉注射与移植组同体积的PBS。对照组大鼠给予碳酸氢钠10ml/Kg皮下注射2h后,经尾静脉注射骨髓MSCs(1×10~7/只)进行干细胞移植。各组大鼠分别于移植后24h、48h、72h处死并留取胃组织标本。按Guth评分标准评价胃黏膜损伤程度。光镜下观察并比较实验组和对照组胃黏膜的损伤情况。免疫组化检测VEGF、EGFR在实验组和对照组的表达差异。
结果:1、骨髓间充质干细胞具有贴壁生长特性,多数为成纤维样梭形细胞,原代细胞12-14天左右贴满培养瓶底,传代细胞的生长速度较原代快,传代后的细胞24h几乎全部贴壁。全骨髓贴壁法与密度梯度离心法相比,细胞自然生长速度较慢,但两者无明显差异(P＞0.05);第3代以后的骨髓MSCs具有良好的均一性,细胞表面抗原CD90,CD44表达为阳性,CD45,CD31表达为阴性;
2、体外采用CFDA SE标记骨髓MSCs后,细胞增殖几乎不受影响,且绿色荧光可随着细胞分裂传给子代。移植后48h,72h,在胃黏膜损伤组大鼠的胃黏膜中检测到带有绿色荧光标记的骨髓MSCs,而在胃黏膜未损伤组则未检测到带有绿色荧光标记的骨髓MSCs;移植后48h和72h移植组雌性大鼠的损伤胃黏膜中大鼠性别决定基因SRY阳性。
3、消炎痛诱导胃黏膜损伤后,实验组大鼠胃黏膜损伤程度较均一,接受骨髓MSCs移植组的大鼠胃黏膜损伤指数较未接受骨髓MSCs移植组有所降低,以移植后72h差异最显著(P＜0.05);
4、免疫组织化学染色结果显示:胃黏膜损伤组大鼠接受骨髓MSCs移植后,胃黏膜内VEGF,EGFR的表达较未接受骨髓MSCs移植组升高,以移植后72h组差异最显著(P＜0.05);
结论:1、大鼠骨髓间充质干细胞体外培养生长稳定,经过换液、传代后细胞逐渐纯化,全骨髓贴壁法方法简单、易于操作、掌握和运用。2、CFDASE体外标记大鼠骨髓MSCs后,可在体内对移植的骨髓MSCs进行示踪,本研究发现经尾静脉移植的骨髓MSCs可定植于损伤的胃黏膜。3、大鼠的骨髓MSCs能一定程度地参与损伤胃黏膜的修复。骨髓MSCs移植后不同时间点损伤大鼠胃黏膜组织中VEGF、EGFR的表达较对照组大鼠明显升高,提示定植于损伤胃黏膜组织的骨髓MSCs可能通过自身分化或分泌某些生物因子的旁分泌途径促进损伤胃黏膜的修复。
Background:Bone marrow mesenchymal stem cells(BMMSCs)are non-hematogenic stem cells isolated from marrow.They have been paid extensive attention in medical field due to their multi-directional differentiation potential, low immunogenicity and can be easily isolated and cultured in vitro. Transplantation of MSCs has already been used in treatment of ischemic and injury diseases.Therefore,stem cell replacement therapy is expected to become a new therapeutic means.
Objective:To study the effect and mechanism of cultured mesenchymal stem cells(MSCs)on the repair of injured gastric mucosa.
Methods:(1)Density gradient centrifugation and differential attachment methods were used to isolate of MSCs from adult Wistar rats and the proliferation ability of the cells was analyzed by MTT examination.The surface antigens of MSCs were detected by flow cytometry.(2)CFDA SE was used to label the MSCs in vitro,then the growth state of MSCs was observed by fluorescence microscope. In situ hybridization technique was used to trace the transplanted cells by detecting the sex-determining gene(SRY)of rats.(3)Fifty-four healthy Wistar rats of 8 weeks old(200g-250g,half of them were female)were randomly divided into three groups:the control group and two gastric mucosa injury groups.Each group had 18 rats.Gastric mucosa injury was induced by hypodermical injection of indomethacinand injected amount was 30mg/Kg.The control group received hypodermical injection of NaHCO_3 with 10ml/Kg.Two hours after injection,one group of rats with gastric mucosa injury and control group were received MSCs(1×10~7/rat)by intravenous injection,while another group anamals were received PBS as the same way.The gastric tissues were dissected respectively 24-h,48-h, 72-h after transplanting of MSCs respectively.The degree of gastric injury was evaluated by the ulcer index(UI).The patho-histological changes of gastric tissues corresponding to different time points were investigated through biological microscope.The difference expression of VEGF and EGFR in the experimental group and control group were detected by immunohistochemistry.
Results:(1)MSCs have the characteristics of adherent growth,The morphology of cultured MSCs was fibroblast-like form.MSCs possessed intensive self-renewal potential and integrated in single layer in 12-14 days after planting.The growth ability of subcultured MSCs was greater than primary cultured MSCs.Nearly all of subcultured MSCs were adhesive in 24 hours. Compare with density gradient centrifugation,the growth rate of MSCs is slower in differential attachment method group.But there was no significant difference. Examination of MSCs revealed that in passage 3 of initial culture almost all adherent cells took on typical morphologies of fibroblastoid cells in vitro and maintained similar morphology with passages.They were positive for CD90, CD44 and were negative for CD31,CD45.
(2)The cell multiplication of MSCs had not been affected after labelling with CFDA SE in vitro.The green fluorescence can be handed down to off-spring with cell division.On the 48-h and 72-h after MSCs transplantation,the CFDA SE labeled cells were found scattered in the gastric of the rats that underwent MSCs transplantation,while these were not detected in the control group at the corresponding points.Moreover,the SRY gene was detected in the injuried gastric mucosa of rats that underwent the transplantation of MSCs derived from male rats 2 weeks after transplantation,while it was not detected in the control group.
(3)The UI was significantly decreased at 72-h after transplanting of MSCs(P＜0.05).
(4)The immunohistochemistry staining of VEGF and EGFR demonstrated that the positive expression of cells were increased in the injuried gastric mucosa of the rats underwent MSCs transplantion than that of control group,it was significantly on 72-h after transplantion.
Conclusion:(1)MSCs can grow stablely in vitro and nonadherent hematopoietic cells were removed through replacing medium.Compared with density gradient centrifugation,the differential attachment method is simple,easy to operate and grasp.(2)The technique of CFDA SE labelling is applicable to be used to trace the transplanted cells in vivo.In present study,it revealed that MSCs could be located in the injured gastri mucosa through intravenous injection. (3)The MSCs of rats may accelerate gastric wound healing course and the mechanism maybe that MSCs could not only differentiate into gastric epithelium but also secreted some biological factors.
骨髓间充质干细胞(Bone marrow mesenchymal stem cells,BMMSCs)是骨髓中一种非造血类的干细胞。近些年来的研究发现,间充质干细胞(mesenchymal stem cells,MSCs)由于具有多向分化潜能、低免疫原性和易于体外扩增等特点,受到医学应用领域的广泛关注。应用骨髓MSCs移植进行细胞替代治疗,目前已被广泛应用于缺血或损伤性疾病以及器官移植、抗免疫排斥反应等研究领域,并取得了初步效果。因此,干细胞替代治疗有望成为临床上一种新的治疗手段。
目的:体外培养和扩增的骨髓间充质干细胞对损伤胃黏膜的修复作用及其机制研究。
方法:1、分别采用全骨髓贴壁法和密度梯度离心法体外培养和扩增Wistar大鼠的骨髓MSCs,应用MTT方法比较两种方法下骨髓MSCs的自然生长曲线,流式细胞仪检测骨髓MSCs表面标志物,对培养、纯化的骨髓MSCs进行鉴定。2、以活体染料羟基荧光素乙酰乙酸(5,6-carboxyfluoresceindiacetate succinimidyl ester,CFDA SE)体外标记骨髓MSCs,荧光显微镜下、488nm波长激发光下观察标记后细胞的生长状态;制备大鼠胃黏膜损伤组织冰冻切片,荧光显微镜下观察移植骨髓MSCs的定植。利用大鼠性别决定基因SRY对移植细胞进行体内示踪。3、选择健康成年Wistar大鼠(体重200g-250g)54只,8周龄,雌雄各半,随机分为对照组和实验组,实验组又分为移植组和非移植组,每组18只。实验组用消炎痛30mg/Kg皮下注射,造成胃损伤模型。造模后2h,移植组大鼠经尾静脉注射骨髓MSCs(1×10~7/只);非移植组大鼠经尾静脉注射与移植组同体积的PBS。对照组大鼠给予碳酸氢钠10ml/Kg皮下注射2h后,经尾静脉注射骨髓MSCs(1×10~7/只)进行干细胞移植。各组大鼠分别于移植后24h、48h、72h处死并留取胃组织标本。按Guth评分标准评价胃黏膜损伤程度。光镜下观察并比较实验组和对照组胃黏膜的损伤情况。免疫组化检测VEGF、EGFR在实验组和对照组的表达差异。
结果:1、骨髓间充质干细胞具有贴壁生长特性,多数为成纤维样梭形细胞,原代细胞12-14天左右贴满培养瓶底,传代细胞的生长速度较原代快,传代后的细胞24h几乎全部贴壁。全骨髓贴壁法与密度梯度离心法相比,细胞自然生长速度较慢,但两者无明显差异(P＞0.05);第3代以后的骨髓MSCs具有良好的均一性,细胞表面抗原CD90,CD44表达为阳性,CD45,CD31表达为阴性;
2、体外采用CFDA SE标记骨髓MSCs后,细胞增殖几乎不受影响,且绿色荧光可随着细胞分裂传给子代。移植后48h,72h,在胃黏膜损伤组大鼠的胃黏膜中检测到带有绿色荧光标记的骨髓MSCs,而在胃黏膜未损伤组则未检测到带有绿色荧光标记的骨髓MSCs;移植后48h和72h移植组雌性大鼠的损伤胃黏膜中大鼠性别决定基因SRY阳性。
3、消炎痛诱导胃黏膜损伤后,实验组大鼠胃黏膜损伤程度较均一,接受骨髓MSCs移植组的大鼠胃黏膜损伤指数较未接受骨髓MSCs移植组有所降低,以移植后72h差异最显著(P＜0.05);
4、免疫组织化学染色结果显示:胃黏膜损伤组大鼠接受骨髓MSCs移植后,胃黏膜内VEGF,EGFR的表达较未接受骨髓MSCs移植组升高,以移植后72h组差异最显著(P＜0.05);
结论:1、大鼠骨髓间充质干细胞体外培养生长稳定,经过换液、传代后细胞逐渐纯化,全骨髓贴壁法方法简单、易于操作、掌握和运用。2、CFDASE体外标记大鼠骨髓MSCs后,可在体内对移植的骨髓MSCs进行示踪,本研究发现经尾静脉移植的骨髓MSCs可定植于损伤的胃黏膜。3、大鼠的骨髓MSCs能一定程度地参与损伤胃黏膜的修复。骨髓MSCs移植后不同时间点损伤大鼠胃黏膜组织中VEGF、EGFR的表达较对照组大鼠明显升高,提示定植于损伤胃黏膜组织的骨髓MSCs可能通过自身分化或分泌某些生物因子的旁分泌途径促进损伤胃黏膜的修复。
Background:Bone marrow mesenchymal stem cells(BMMSCs)are non-hematogenic stem cells isolated from marrow.They have been paid extensive attention in medical field due to their multi-directional differentiation potential, low immunogenicity and can be easily isolated and cultured in vitro. Transplantation of MSCs has already been used in treatment of ischemic and injury diseases.Therefore,stem cell replacement therapy is expected to become a new therapeutic means.
Objective:To study the effect and mechanism of cultured mesenchymal stem cells(MSCs)on the repair of injured gastric mucosa.
Methods:(1)Density gradient centrifugation and differential attachment methods were used to isolate of MSCs from adult Wistar rats and the proliferation ability of the cells was analyzed by MTT examination.The surface antigens of MSCs were detected by flow cytometry.(2)CFDA SE was used to label the MSCs in vitro,then the growth state of MSCs was observed by fluorescence microscope. In situ hybridization technique was used to trace the transplanted cells by detecting the sex-determining gene(SRY)of rats.(3)Fifty-four healthy Wistar rats of 8 weeks old(200g-250g,half of them were female)were randomly divided into three groups:the control group and two gastric mucosa injury groups.Each group had 18 rats.Gastric mucosa injury was induced by hypodermical injection of indomethacinand injected amount was 30mg/Kg.The control group received hypodermical injection of NaHCO_3 with 10ml/Kg.Two hours after injection,one group of rats with gastric mucosa injury and control group were received MSCs(1×10~7/rat)by intravenous injection,while another group anamals were received PBS as the same way.The gastric tissues were dissected respectively 24-h,48-h, 72-h after transplanting of MSCs respectively.The degree of gastric injury was evaluated by the ulcer index(UI).The patho-histological changes of gastric tissues corresponding to different time points were investigated through biological microscope.The difference expression of VEGF and EGFR in the experimental group and control group were detected by immunohistochemistry.
Results:(1)MSCs have the characteristics of adherent growth,The morphology of cultured MSCs was fibroblast-like form.MSCs possessed intensive self-renewal potential and integrated in single layer in 12-14 days after planting.The growth ability of subcultured MSCs was greater than primary cultured MSCs.Nearly all of subcultured MSCs were adhesive in 24 hours. Compare with density gradient centrifugation,the growth rate of MSCs is slower in differential attachment method group.But there was no significant difference. Examination of MSCs revealed that in passage 3 of initial culture almost all adherent cells took on typical morphologies of fibroblastoid cells in vitro and maintained similar morphology with passages.They were positive for CD90, CD44 and were negative for CD31,CD45.
(2)The cell multiplication of MSCs had not been affected after labelling with CFDA SE in vitro.The green fluorescence can be handed down to off-spring with cell division.On the 48-h and 72-h after MSCs transplantation,the CFDA SE labeled cells were found scattered in the gastric of the rats that underwent MSCs transplantation,while these were not detected in the control group at the corresponding points.Moreover,the SRY gene was detected in the injuried gastric mucosa of rats that underwent the transplantation of MSCs derived from male rats 2 weeks after transplantation,while it was not detected in the control group.
(3)The UI was significantly decreased at 72-h after transplanting of MSCs(P＜0.05).
(4)The immunohistochemistry staining of VEGF and EGFR demonstrated that the positive expression of cells were increased in the injuried gastric mucosa of the rats underwent MSCs transplantion than that of control group,it was significantly on 72-h after transplantion.
Conclusion:(1)MSCs can grow stablely in vitro and nonadherent hematopoietic cells were removed through replacing medium.Compared with density gradient centrifugation,the differential attachment method is simple,easy to operate and grasp.(2)The technique of CFDA SE labelling is applicable to be used to trace the transplanted cells in vivo.In present study,it revealed that MSCs could be located in the injured gastri mucosa through intravenous injection. (3)The MSCs of rats may accelerate gastric wound healing course and the mechanism maybe that MSCs could not only differentiate into gastric epithelium but also secreted some biological factors.
引文
[1].朱鸣,吴本俨.胃酸减少导致的细菌过度繁殖与感染[J].空军总医院学报,2007,23(3):165-168.
[2].Lee M,Feldman M.Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirin-induced injury in rats.Gastroenterology[J].1994,107(6):1746-1750.
[3].李红涛,吴开春,李彩宁等.血清胃泌素对老年人慢性萎缩性胃炎的诊断[J].中华老年医学杂志,2004,23(4):238-340.
[4].Kapadia CR.Gastric atrophy,metaplasia,and dysplasia:a clinical perspective[J].J Clin Gastroenterol,2003,36(5 Suppl):S29-S36.
[5].Xia HH,Kalantar JS,Talley NJ,et al.Antral-Type Mucosa in the Gastric Incisura,Body,and Fundus(Antralization):a link between helicobacter pylori infection and intestinal metaplasia?[J].Am J Gastroenterol,2000,95(1):114-121.
[6].Whiting JL,Sigurdsson A,Rowlands DC,et al.The long term results of endoscopic surveillance of premalignant gastric lesions[J].Gut,2002,50(3):378-381.
[7].Prockop DJ.Marrow stromal cells as stem cells for nonhematopoietic tissues[J].Science,1997,276(5309):71-74.
[8].Krause DS.Plasticity of marrow-derived stem cells[J].Gene Therapy,2002,9(11):754-758.
[9].Bianco P,Riminucci M,Gronthos S,et al.Bone marrow stromal stem cells:Nature,biology,and potential applications[J].Stem Cells,2001,19(3):180-192.
[10].Orlic D.Adult bone marrow stem cells regenerate myocardium in ischemic heart disease[J].Ann N Y Acad Sci,2003,996(5):152-157.
[11].Plumas J,Chaperot L,Richard M J,et al.Mesenchymal stem cells induce apoptosis of activated T cells[J].Leukemia,2005,19(9):1597-1604.
[12].Guo Z,Yang J,Liu X,et al.Biological features of mesenchymal stem cells from human bone marrow[J].Chinese Medical Journal,2001,114(9):950-953.
[13].Lodie TA,Blickarz CE,Devarakonda TJ,et al.Systematic analysis of reportedly distinct populations of multipotent bone marrow-derived stem cells reveals a lack of distinction[J].Tissue Eng,2002,8(5):739-751.
[14].薛庆善,肖渝平,林娟.体外培养的技术和原理[M].科学出版社,2001,第1版:469.
[15].Colter DC,Class R,DiGirolamo CM,et al.Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow[J].Proc Natl Acad Sci USA.2000,97(7):3213-3218.
[16].Phinney DG,Kopen G,Isaacson RL,et al.Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice:Variations in yield,growth,and differentiation[J].J Cellular Biochemistry.1999,72(4):570-585.
[17].Jorgense C,Djorad F,Apparailly F,et al.Engineering mesenchymal stem cells for immunotherapy[J].Gene Ther,2003,10(10):928-931.
[18].Pittenger MF,Mackay AM,Beck SC,et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284(5411):143-147.
[19].Javazon EH,Colter DC,Schwarz EJ,et al.Rat marrow stromal cells are more sensitive to planting density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells[J].Stem Cells,2001,19(3):219-225.
[1].许剑,徐格林,刘新峰.骨髓基质干细胞的标记示踪技术及其应用[J].中国临床神经科学,2006,14(2):197-201.
[2].Dunnwald M,Chinnathambi S,Alexandrunas D,et al.Mouse epidermal stem cells proceed through the cell cycle[J].J Cel 1 Physiol,2003,195(1):194-201.
[3].Sakai T,Li RK,Weisel RD,et al.Autologous heart cell transplantation,improve cardiac function after myocardial injury[J].Ann Thorac S urg,1999,68(7):2074-2081.
[4].Ishiwata N,Suzuki S,Ando,et al.Characteristics and biodistribution of cationic liposomes and their DNA complexes[J].J Control Rel,2000,69(1):139-148.
[5].Arhsall E.Gene therapy death prompts review of adenovirus vector [J].Science,2000,286(3):2244-2245.
[6].Parish CR.Fluorescent dyes for lymphocyte migration and proliferation studies[J].Immunol Cell Biol,1999,77(6):499-508.
[7].Weston SA,Parish CR.New flurescent dyes for lymphocyte migration studies:analysis by flow cytometry and fluorescence microscopy[J].J Immunol Methods,1990,133(1):87-97.
[8].Gruber HE,Leslie KP,Ingraim JA,et al.Optimization of 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester for labeling human intervertebral disc cells in vitro[J].Biotech Histochem,2000,75(3):118-123.
[9].付霞菲,何援利.大鼠间充质干细胞的体外分离培养及 CFSE 标记[J].解放军医学杂志,2007,32(5):464-466.
[10].陈必成,昌盛,杜敦峰等.羟基荧光素乙酰乙酸在移植免疫研究中的应用.医学研究生学报[J],2005,18(2):121-124.
[1].Guth PH,Paulsen G.Aspirin-induced gastric injury in the rat:histologic changes and sucralfate cytoprotection.Proc Soc Exp Biol Med,1987,184(4):423-428.
[2].邝贺龄.消化性溃疡(下),国外医学内科分册;2002,29(7):277.
[3].卢文丽,方肇勤等.常见胃溃疡模型小鼠组织病理变化及差异.中华中医药学刊,2008,26(3):551-555.
[4].Boku K,Ohno T,Saeki T,et al.Adaptive cytoprotection mediated by prostaglandin Ⅰ(2)is attributable to sensitization of CRGP-containing sensory nerves[J].Gastroenterology,2001,120(1):134-143.
[5].Arun M,Asha VV.Gastroprotective effect of Dodonaea viscosa on various expermental ulcer models.Journal of Ethnopharmacology,2008,118(3):460-465.
[6].Wallace JL,Granger DN.The cellular and molecular basis ofgastic mucosal defense.FASEB J,1996,10(7):731-740.
[7].Giannakis M,Stappenbeck TS,Mills JC,et al.Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches.J Biol Chem,2006,281(16):11292-11300.
[8].Jones MK,Itani RM,Wang H,et al.Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury.Am J Physiol,1999,276(6 Pt 1):G1345-1355.
[9].Szabo IL,Kawanaka H,Jones MK,et al.Activation of hypoxia inducible factor-1 alpha in gastric mucosa in response to ethanol injury:a trigger for angiogenesis?Life Sci.2001,9;69(25-26):3035-3044.
[10].Matsui Y,Mitsuyama K,Tomiyasu N,et al.Efficacy of vascular endothelial growth factor in the treatment of experimental gastric injury.Digestion.2002,66(2):99-105.
[11].Milani S,Calabro A.Role of growth factors and their receptors in gastric ulcer healing.Micros Res Tech.2001,53(5):360-371.
[12].Teyssen S,Singer MV.Alcohol-related diseases of oesophyagus and stomach.Best Pract Res Clin Gastroenterol.2003;17(4):557-573.
[13].李兆申.胃黏膜损伤与保护-基础与临床[M].上海:上海科学技术出版社,2004:269-274.
[14].许春娣.表皮生长因子在消化性溃疡愈合中的作用[J].国外医学儿科学分册,1997,24(3):123-126.
[15].刘磊,白玉贤.EGFR 靶向药物治疗胃肠道肿瘤的新进展.实用肿瘤学杂志,2008,22(4):382-384.
[16].Wollert KC,Meyer GP,Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction:The BOOST randomized controlled clinical trial.Lancet,2004,364(9429):141-148.
[17].Stamm C,Westphal B,Kleine HD,et al.Autologous bone-marrow stem-celltransplantation for myocardial regeneration.Lancet,2003,361(9351):45-46.
[18].Quarto R,Mastrogiacomo M,Cancedda R,et al.Repair of large bone defects with the use of autologous bone marrow stromal cells.N Engl J Med,2001,344(5):385-386.
[19].Weiss ML,Medicetty,Bledsoe AR,et al.Human umbilical cord matrix stem cells:preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease.Stem Cells,2006,24(3):781-792.
[20].Sarosi G,Brown G,Jaiseal K,et al.Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett's esophagus[J].Dis Esophagus,2008,21(1):43-50.
[21].Brittan M,Chance V,Elia G,et al.A regenerative role for bone marrow following experimental colitis:contribution to neovasculogenesis and myofibroblasts[J].Gastroenterology,2005,128(7):1984-1995.
[22].Andoh A,Bamba S,Fujiyama Y,et al.Colonic subepithelial myofibroblasts in mucosal inflammation and repair:contuibution of bone marrow-derived stem cells to the gut regenerative response[J].J Gastroenterol,2005,40(12):1089-1099.
[23].Hayashi Y,Tsuji S,Tsujii M,et al.The transdifferentiation of bone-marrow-derived cells in colonic mucosal regeneration after dextran-sulfate-sodium-induced colitis in mice[J].Pharmacology,2007,80(4):193-199.
[24].Hayashi Y,Tuji S,Tsujii M,et al.Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats[J].Am J Physiol Gastrointest Liver Physiol,2008,294(3):G778-G786.
[25].Preston SL,Alison MR,Forbes SJ,et al.The new stem cell biology:something for everyone[J].Mol Pathol,2003,56(2):86-96.
[26].Da Silva Meirelles L,Chagastelles PC,et al.Mesenchymal stem cells reside in virtually all post-natal organs and tissues[J].J Cell Sci,2006,119(Pt 11):2204-2213.
[27].Wexler SA,Donaldson C,Denning-Kendall P,et al.Adult bone marrow is a rich sourse of human mesenchymal stem cells but umbilical cord and mobilized adult blood are not[J].Br J Hameratol,2003,121(2):368-374.
[28].Zvaifler NJ,Marinova-Mutafchieva L,et al.Mesenchymal precursor cells in the blood of normal individuals[J].Arthritis Res,2000,2(6):477-488.
[29].Kuznetsov SA,Mankani MH,Adams G,et al.Circulating skeletal stem cells[J].J Cell Biol,2001,153(5):1133-1140.
[30].Nagaya N,Fujii T,Iwase T,et al.Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis[J].Am J Physiol Heart Circ Physiol,2004,287(6):2670-2676.
[31].Uccelli A,Moretta L,Pistoia V,et al.Immunoregulatory ruction of mesenchymal stem cells[J].Eur J Immunol,2006,36(10):2566-2573.
[32].Di Nicola M,Carlo-Stella C,Magni M,et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli[J].Blood,2002,99(10):3838-3843.
[33].Okamoto R,Yajima T,Yamazaki M,et al.Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract[J].Nat Med,2002,8 (9):1011-1017.
[34].Houghton J,Stoicov C,Nomura S,et al.Gastric cancer originating from bone marrow-derived cells.Science,2004,306(5701):1568-1571.
[35].Serakinci N,Guldberg P,Burns JS,et al.Aldult human mesenchymal stem cell as a target for neoplastic transformation[J].Oncogene,2004,23(29):5095-5098.
[1].Ott HC,Matthiesen TS,Brechtken J,et al.The adult human heart as a source for stem cells:repair strategies with embryonic-like progenitor cells[J].Nat Clin Pract Cardiovasc Med,2007,4(Suppl 1):S27-39.
[2].赵宇辉.脑损伤的修复与神经干细胞移植的研究进展[J].陕西医学杂志,2005,34(1):86-88.
[3].Ferrari G,Cusella-De Angelis G,Coletta M,et al.Muscle regeneration by bone marrow-derived myogenic progenitors[J].Science,1998,279(5356):1528-1530.
[4].Onyia JE,Clapp DW,Long H,et al.Osteoprogenitor cells as targets for exvivo gene transfer[J].J Bone Miner Res,1998,13(1):20-30.
[5].De Bail C,Dell Accio F,Tylzanowski P,et al.Multipotent mesenchymal stem cells from adult human synovial membrane.Arthritis Rheum,2001,44:1928-1942.
[6].Gronthos S,Mankani M,Brahim J,et al.Postnatal human dental pulp stem cells(DPSCs)in vitro and in vivo.Proc Natl Acad Sci USA,2000,97(25):13625-13630.
[7].Seo BM,Miura M,Gronthos S,et al.Investigation of multipotent postnatal stem cells from human periodontal ligament.Lancet,2004,364:149-155.
[8].Fukuchi Y,Nakajima H,Sugiyama D,et al.Human placenta-derived cells have mesenchymal stem/progenitor cell potential.Stem Cells,2004,22:649-658.
[9].da Silva Meirelles L,Chagastelles PC,Nardi NB.Mesenchymal stem cells reside in virtually all post-natal organs and tissres.J Cell Sci,2006,119:2204-2213.
[10].Plumas J,Chaperor L,Richard M J,et al.Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia,2005,19:1597-1604.
[11].Campagnoli C,Roberts IA,Kumar S,et al.Identification of mesenchymal stem/progenitor cells in human first trimester fetal blood,liver,and bone marrow.Blood,2001,98(8):2396-2402.
[12].Jorgense C,Djorad F,Apparailly F,et al.Engineering mesenchymal stem cells for immunotherapy.Gene Ther,2003,10:928-931.
[13].Pittenger MF,Mackay AM,Beck SC,et al.Multi-line-age potential of adult humanmesenchymal stem cells.Science,1999,284(5411):143.
[14].Kofidis T,de Bruin JL,Tanaka M,et al.They are not stealthy in the heart:embryonic stem cells trigger cell infilatration,humoral and T-lymphocyte-based host immune response.Eur J Cardiothorac Surg,2005,28:461-466.
[15].El-Badri NS,Maheshwari A,Sanberg PR.Mesenchymal stem cells in autoimmune disease.Stem Cells Dev,2004,13:463-472.
[16].Bartholomew A,Sturgeon C,Siatskas M,et al.Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo.Exp Hematol,2002,30:42-48.
[17].Le Blanc K.Immunomodulatory effects of fetal and adult mesenchymal stem cells.Cytotherapy,2003,5:485-489.
[18].Di Nicola M,Carlo-Stella C,Magni M,et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.Blood,2002,99:3838-3843.
[19].Tse WT,Pendleton JD,Beyer WM,et al.Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation.Transplantation,2003,75:389-397.
[20].Rasmusson I,Ringden O,Sundberg B,et al.Messenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanismas.Exp Cell Res,2005,305:33-41.
[21].Rasmusson I,Ringden O,Sundberg B,et al.Mesenchymal stem cells inhibit the formation of cytotoxic Tlymphocytes,but not activated cytotoxic T lymphocytes or natural koller cells.Transplantation,2003,76:1208-1213.
[22].Ryan JM,Barry FP,Murphy JM,et al.Mesenchymal stem cells avoid allogeneic rejection.J Inflamm(Lond),2005,2:8.
[23].王天佑,展玉涛.胃干细胞[J].世界华人消化杂志,2003,1l(11):1727-1730.
[24].赵向阳,陈凛.胃肠干细胞与胃肠肿瘤关系研究进展[J].中华胃肠外科杂志,2006,9(3):272-274.
[25].郑永波,吴承堂.肠上皮干细胞研究进展[J].细胞生物学杂志,2004,26(1):6-9.
[26].胡建昆,陈心足,周总光.干细胞与组织工程在肠道的研究进展[J].中国修复重建外科杂志,2007,2l(2):175-179.
[27].Marshman E,Booth C,Potten CS.The intestinal epithelial stem cell[J].Bioessays,2002,24(1):91-98.
[28].潘国宗,许国铭,郭慧平等.北京上海胃食管反流症状的流行病学调查[J].中华消化杂志,1999,19(4):223-225.
[29].李兆申,许国铭,刘婧等.上海地区成年人胃食管反流病流行病学调查Ⅰ:胃食管反流症状及相关因素调查[J].解放军医学杂志,1997,22(4):259-261.
[30].吴本俨,邵勇,李园等.北京地区老年人胃食管反流症状流行病学调查[J].军医进修学院学报,2004,25(2):110-112.
[31].朱鸣,吴本俨.胃酸减少导致的细菌过度繁殖与感染[J].空军总医院学报,2007,23(3):165-168.
[32].Sarosi G,Brown G,Jaiswal K,et al.Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett's esophagus[J].Dis Esophagus,2008,21(1):43-50.
[33].Michael M,Epperly,Guo HL,Shen HM,et al.Bone Marrow Origin of cells with capacity for homing and differentiation to esophageal squamous epithelium.Radiat[J].Res,2004,162:233-240.
[34].魏亚明,聂玉强,李瑜元,等.炎症性肠病及其干细胞移植再生修复[J].世界华人消化杂志,2006,14(13):1314-1317.
[35].杨立新,钱家鸣.造血干细胞移植与炎症性肠病[J].中华内科杂志,2005, 44(1):65-67.
[36].孙涛,王少鑫.骨髓干细胞移植诱导胃肠上皮细胞再生的研究进展[J].中华内科杂志,2006,45(1):77-78.
[2].Lee M,Feldman M.Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirin-induced injury in rats.Gastroenterology[J].1994,107(6):1746-1750.
[3].李红涛,吴开春,李彩宁等.血清胃泌素对老年人慢性萎缩性胃炎的诊断[J].中华老年医学杂志,2004,23(4):238-340.
[4].Kapadia CR.Gastric atrophy,metaplasia,and dysplasia:a clinical perspective[J].J Clin Gastroenterol,2003,36(5 Suppl):S29-S36.
[5].Xia HH,Kalantar JS,Talley NJ,et al.Antral-Type Mucosa in the Gastric Incisura,Body,and Fundus(Antralization):a link between helicobacter pylori infection and intestinal metaplasia?[J].Am J Gastroenterol,2000,95(1):114-121.
[6].Whiting JL,Sigurdsson A,Rowlands DC,et al.The long term results of endoscopic surveillance of premalignant gastric lesions[J].Gut,2002,50(3):378-381.
[7].Prockop DJ.Marrow stromal cells as stem cells for nonhematopoietic tissues[J].Science,1997,276(5309):71-74.
[8].Krause DS.Plasticity of marrow-derived stem cells[J].Gene Therapy,2002,9(11):754-758.
[9].Bianco P,Riminucci M,Gronthos S,et al.Bone marrow stromal stem cells:Nature,biology,and potential applications[J].Stem Cells,2001,19(3):180-192.
[10].Orlic D.Adult bone marrow stem cells regenerate myocardium in ischemic heart disease[J].Ann N Y Acad Sci,2003,996(5):152-157.
[11].Plumas J,Chaperot L,Richard M J,et al.Mesenchymal stem cells induce apoptosis of activated T cells[J].Leukemia,2005,19(9):1597-1604.
[12].Guo Z,Yang J,Liu X,et al.Biological features of mesenchymal stem cells from human bone marrow[J].Chinese Medical Journal,2001,114(9):950-953.
[13].Lodie TA,Blickarz CE,Devarakonda TJ,et al.Systematic analysis of reportedly distinct populations of multipotent bone marrow-derived stem cells reveals a lack of distinction[J].Tissue Eng,2002,8(5):739-751.
[14].薛庆善,肖渝平,林娟.体外培养的技术和原理[M].科学出版社,2001,第1版:469.
[15].Colter DC,Class R,DiGirolamo CM,et al.Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow[J].Proc Natl Acad Sci USA.2000,97(7):3213-3218.
[16].Phinney DG,Kopen G,Isaacson RL,et al.Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice:Variations in yield,growth,and differentiation[J].J Cellular Biochemistry.1999,72(4):570-585.
[17].Jorgense C,Djorad F,Apparailly F,et al.Engineering mesenchymal stem cells for immunotherapy[J].Gene Ther,2003,10(10):928-931.
[18].Pittenger MF,Mackay AM,Beck SC,et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284(5411):143-147.
[19].Javazon EH,Colter DC,Schwarz EJ,et al.Rat marrow stromal cells are more sensitive to planting density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells[J].Stem Cells,2001,19(3):219-225.
[1].许剑,徐格林,刘新峰.骨髓基质干细胞的标记示踪技术及其应用[J].中国临床神经科学,2006,14(2):197-201.
[2].Dunnwald M,Chinnathambi S,Alexandrunas D,et al.Mouse epidermal stem cells proceed through the cell cycle[J].J Cel 1 Physiol,2003,195(1):194-201.
[3].Sakai T,Li RK,Weisel RD,et al.Autologous heart cell transplantation,improve cardiac function after myocardial injury[J].Ann Thorac S urg,1999,68(7):2074-2081.
[4].Ishiwata N,Suzuki S,Ando,et al.Characteristics and biodistribution of cationic liposomes and their DNA complexes[J].J Control Rel,2000,69(1):139-148.
[5].Arhsall E.Gene therapy death prompts review of adenovirus vector [J].Science,2000,286(3):2244-2245.
[6].Parish CR.Fluorescent dyes for lymphocyte migration and proliferation studies[J].Immunol Cell Biol,1999,77(6):499-508.
[7].Weston SA,Parish CR.New flurescent dyes for lymphocyte migration studies:analysis by flow cytometry and fluorescence microscopy[J].J Immunol Methods,1990,133(1):87-97.
[8].Gruber HE,Leslie KP,Ingraim JA,et al.Optimization of 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester for labeling human intervertebral disc cells in vitro[J].Biotech Histochem,2000,75(3):118-123.
[9].付霞菲,何援利.大鼠间充质干细胞的体外分离培养及 CFSE 标记[J].解放军医学杂志,2007,32(5):464-466.
[10].陈必成,昌盛,杜敦峰等.羟基荧光素乙酰乙酸在移植免疫研究中的应用.医学研究生学报[J],2005,18(2):121-124.
[1].Guth PH,Paulsen G.Aspirin-induced gastric injury in the rat:histologic changes and sucralfate cytoprotection.Proc Soc Exp Biol Med,1987,184(4):423-428.
[2].邝贺龄.消化性溃疡(下),国外医学内科分册;2002,29(7):277.
[3].卢文丽,方肇勤等.常见胃溃疡模型小鼠组织病理变化及差异.中华中医药学刊,2008,26(3):551-555.
[4].Boku K,Ohno T,Saeki T,et al.Adaptive cytoprotection mediated by prostaglandin Ⅰ(2)is attributable to sensitization of CRGP-containing sensory nerves[J].Gastroenterology,2001,120(1):134-143.
[5].Arun M,Asha VV.Gastroprotective effect of Dodonaea viscosa on various expermental ulcer models.Journal of Ethnopharmacology,2008,118(3):460-465.
[6].Wallace JL,Granger DN.The cellular and molecular basis ofgastic mucosal defense.FASEB J,1996,10(7):731-740.
[7].Giannakis M,Stappenbeck TS,Mills JC,et al.Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches.J Biol Chem,2006,281(16):11292-11300.
[8].Jones MK,Itani RM,Wang H,et al.Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury.Am J Physiol,1999,276(6 Pt 1):G1345-1355.
[9].Szabo IL,Kawanaka H,Jones MK,et al.Activation of hypoxia inducible factor-1 alpha in gastric mucosa in response to ethanol injury:a trigger for angiogenesis?Life Sci.2001,9;69(25-26):3035-3044.
[10].Matsui Y,Mitsuyama K,Tomiyasu N,et al.Efficacy of vascular endothelial growth factor in the treatment of experimental gastric injury.Digestion.2002,66(2):99-105.
[11].Milani S,Calabro A.Role of growth factors and their receptors in gastric ulcer healing.Micros Res Tech.2001,53(5):360-371.
[12].Teyssen S,Singer MV.Alcohol-related diseases of oesophyagus and stomach.Best Pract Res Clin Gastroenterol.2003;17(4):557-573.
[13].李兆申.胃黏膜损伤与保护-基础与临床[M].上海:上海科学技术出版社,2004:269-274.
[14].许春娣.表皮生长因子在消化性溃疡愈合中的作用[J].国外医学儿科学分册,1997,24(3):123-126.
[15].刘磊,白玉贤.EGFR 靶向药物治疗胃肠道肿瘤的新进展.实用肿瘤学杂志,2008,22(4):382-384.
[16].Wollert KC,Meyer GP,Lotz J,et al.Intracoronary autologous bone-marrow cell transfer after myocardial infarction:The BOOST randomized controlled clinical trial.Lancet,2004,364(9429):141-148.
[17].Stamm C,Westphal B,Kleine HD,et al.Autologous bone-marrow stem-celltransplantation for myocardial regeneration.Lancet,2003,361(9351):45-46.
[18].Quarto R,Mastrogiacomo M,Cancedda R,et al.Repair of large bone defects with the use of autologous bone marrow stromal cells.N Engl J Med,2001,344(5):385-386.
[19].Weiss ML,Medicetty,Bledsoe AR,et al.Human umbilical cord matrix stem cells:preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease.Stem Cells,2006,24(3):781-792.
[20].Sarosi G,Brown G,Jaiseal K,et al.Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett's esophagus[J].Dis Esophagus,2008,21(1):43-50.
[21].Brittan M,Chance V,Elia G,et al.A regenerative role for bone marrow following experimental colitis:contribution to neovasculogenesis and myofibroblasts[J].Gastroenterology,2005,128(7):1984-1995.
[22].Andoh A,Bamba S,Fujiyama Y,et al.Colonic subepithelial myofibroblasts in mucosal inflammation and repair:contuibution of bone marrow-derived stem cells to the gut regenerative response[J].J Gastroenterol,2005,40(12):1089-1099.
[23].Hayashi Y,Tsuji S,Tsujii M,et al.The transdifferentiation of bone-marrow-derived cells in colonic mucosal regeneration after dextran-sulfate-sodium-induced colitis in mice[J].Pharmacology,2007,80(4):193-199.
[24].Hayashi Y,Tuji S,Tsujii M,et al.Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats[J].Am J Physiol Gastrointest Liver Physiol,2008,294(3):G778-G786.
[25].Preston SL,Alison MR,Forbes SJ,et al.The new stem cell biology:something for everyone[J].Mol Pathol,2003,56(2):86-96.
[26].Da Silva Meirelles L,Chagastelles PC,et al.Mesenchymal stem cells reside in virtually all post-natal organs and tissues[J].J Cell Sci,2006,119(Pt 11):2204-2213.
[27].Wexler SA,Donaldson C,Denning-Kendall P,et al.Adult bone marrow is a rich sourse of human mesenchymal stem cells but umbilical cord and mobilized adult blood are not[J].Br J Hameratol,2003,121(2):368-374.
[28].Zvaifler NJ,Marinova-Mutafchieva L,et al.Mesenchymal precursor cells in the blood of normal individuals[J].Arthritis Res,2000,2(6):477-488.
[29].Kuznetsov SA,Mankani MH,Adams G,et al.Circulating skeletal stem cells[J].J Cell Biol,2001,153(5):1133-1140.
[30].Nagaya N,Fujii T,Iwase T,et al.Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis[J].Am J Physiol Heart Circ Physiol,2004,287(6):2670-2676.
[31].Uccelli A,Moretta L,Pistoia V,et al.Immunoregulatory ruction of mesenchymal stem cells[J].Eur J Immunol,2006,36(10):2566-2573.
[32].Di Nicola M,Carlo-Stella C,Magni M,et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli[J].Blood,2002,99(10):3838-3843.
[33].Okamoto R,Yajima T,Yamazaki M,et al.Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract[J].Nat Med,2002,8 (9):1011-1017.
[34].Houghton J,Stoicov C,Nomura S,et al.Gastric cancer originating from bone marrow-derived cells.Science,2004,306(5701):1568-1571.
[35].Serakinci N,Guldberg P,Burns JS,et al.Aldult human mesenchymal stem cell as a target for neoplastic transformation[J].Oncogene,2004,23(29):5095-5098.
[1].Ott HC,Matthiesen TS,Brechtken J,et al.The adult human heart as a source for stem cells:repair strategies with embryonic-like progenitor cells[J].Nat Clin Pract Cardiovasc Med,2007,4(Suppl 1):S27-39.
[2].赵宇辉.脑损伤的修复与神经干细胞移植的研究进展[J].陕西医学杂志,2005,34(1):86-88.
[3].Ferrari G,Cusella-De Angelis G,Coletta M,et al.Muscle regeneration by bone marrow-derived myogenic progenitors[J].Science,1998,279(5356):1528-1530.
[4].Onyia JE,Clapp DW,Long H,et al.Osteoprogenitor cells as targets for exvivo gene transfer[J].J Bone Miner Res,1998,13(1):20-30.
[5].De Bail C,Dell Accio F,Tylzanowski P,et al.Multipotent mesenchymal stem cells from adult human synovial membrane.Arthritis Rheum,2001,44:1928-1942.
[6].Gronthos S,Mankani M,Brahim J,et al.Postnatal human dental pulp stem cells(DPSCs)in vitro and in vivo.Proc Natl Acad Sci USA,2000,97(25):13625-13630.
[7].Seo BM,Miura M,Gronthos S,et al.Investigation of multipotent postnatal stem cells from human periodontal ligament.Lancet,2004,364:149-155.
[8].Fukuchi Y,Nakajima H,Sugiyama D,et al.Human placenta-derived cells have mesenchymal stem/progenitor cell potential.Stem Cells,2004,22:649-658.
[9].da Silva Meirelles L,Chagastelles PC,Nardi NB.Mesenchymal stem cells reside in virtually all post-natal organs and tissres.J Cell Sci,2006,119:2204-2213.
[10].Plumas J,Chaperor L,Richard M J,et al.Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia,2005,19:1597-1604.
[11].Campagnoli C,Roberts IA,Kumar S,et al.Identification of mesenchymal stem/progenitor cells in human first trimester fetal blood,liver,and bone marrow.Blood,2001,98(8):2396-2402.
[12].Jorgense C,Djorad F,Apparailly F,et al.Engineering mesenchymal stem cells for immunotherapy.Gene Ther,2003,10:928-931.
[13].Pittenger MF,Mackay AM,Beck SC,et al.Multi-line-age potential of adult humanmesenchymal stem cells.Science,1999,284(5411):143.
[14].Kofidis T,de Bruin JL,Tanaka M,et al.They are not stealthy in the heart:embryonic stem cells trigger cell infilatration,humoral and T-lymphocyte-based host immune response.Eur J Cardiothorac Surg,2005,28:461-466.
[15].El-Badri NS,Maheshwari A,Sanberg PR.Mesenchymal stem cells in autoimmune disease.Stem Cells Dev,2004,13:463-472.
[16].Bartholomew A,Sturgeon C,Siatskas M,et al.Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo.Exp Hematol,2002,30:42-48.
[17].Le Blanc K.Immunomodulatory effects of fetal and adult mesenchymal stem cells.Cytotherapy,2003,5:485-489.
[18].Di Nicola M,Carlo-Stella C,Magni M,et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.Blood,2002,99:3838-3843.
[19].Tse WT,Pendleton JD,Beyer WM,et al.Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation.Transplantation,2003,75:389-397.
[20].Rasmusson I,Ringden O,Sundberg B,et al.Messenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanismas.Exp Cell Res,2005,305:33-41.
[21].Rasmusson I,Ringden O,Sundberg B,et al.Mesenchymal stem cells inhibit the formation of cytotoxic Tlymphocytes,but not activated cytotoxic T lymphocytes or natural koller cells.Transplantation,2003,76:1208-1213.
[22].Ryan JM,Barry FP,Murphy JM,et al.Mesenchymal stem cells avoid allogeneic rejection.J Inflamm(Lond),2005,2:8.
[23].王天佑,展玉涛.胃干细胞[J].世界华人消化杂志,2003,1l(11):1727-1730.
[24].赵向阳,陈凛.胃肠干细胞与胃肠肿瘤关系研究进展[J].中华胃肠外科杂志,2006,9(3):272-274.
[25].郑永波,吴承堂.肠上皮干细胞研究进展[J].细胞生物学杂志,2004,26(1):6-9.
[26].胡建昆,陈心足,周总光.干细胞与组织工程在肠道的研究进展[J].中国修复重建外科杂志,2007,2l(2):175-179.
[27].Marshman E,Booth C,Potten CS.The intestinal epithelial stem cell[J].Bioessays,2002,24(1):91-98.
[28].潘国宗,许国铭,郭慧平等.北京上海胃食管反流症状的流行病学调查[J].中华消化杂志,1999,19(4):223-225.
[29].李兆申,许国铭,刘婧等.上海地区成年人胃食管反流病流行病学调查Ⅰ:胃食管反流症状及相关因素调查[J].解放军医学杂志,1997,22(4):259-261.
[30].吴本俨,邵勇,李园等.北京地区老年人胃食管反流症状流行病学调查[J].军医进修学院学报,2004,25(2):110-112.
[31].朱鸣,吴本俨.胃酸减少导致的细菌过度繁殖与感染[J].空军总医院学报,2007,23(3):165-168.
[32].Sarosi G,Brown G,Jaiswal K,et al.Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett's esophagus[J].Dis Esophagus,2008,21(1):43-50.
[33].Michael M,Epperly,Guo HL,Shen HM,et al.Bone Marrow Origin of cells with capacity for homing and differentiation to esophageal squamous epithelium.Radiat[J].Res,2004,162:233-240.
[34].魏亚明,聂玉强,李瑜元,等.炎症性肠病及其干细胞移植再生修复[J].世界华人消化杂志,2006,14(13):1314-1317.
[35].杨立新,钱家鸣.造血干细胞移植与炎症性肠病[J].中华内科杂志,2005, 44(1):65-67.
[36].孙涛,王少鑫.骨髓干细胞移植诱导胃肠上皮细胞再生的研究进展[J].中华内科杂志,2006,45(1):77-78.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |