体外扩增心脏侧群细胞参与心肌重建的实验研究
|
摘要
背景
SP(side population)细胞是近年来人们关注的一群成体干细胞。1996年Goodell等首先发现于骨髓,并称之为SP细胞(中文称之为边缘群或侧群细胞)。现已发现,SP细胞在成体组织中广泛存在。来源于心脏的SP细胞(CSP)在体外与心肌细胞共培养条件下能向心肌细胞分化。直接回输体内实验也证实CSP细胞能够形成心肌样细胞,参与损伤心肌的修复。然而成体心脏组织中,CSP细胞含量较少,不能满足临床治疗的需要。因此本课题进一步探讨CSP细胞通过体外培养进行扩增的可能性及其扩增细胞参与心肌重建的能力。
目的:1.观察CSP细胞能否体外培养扩增。2.扩增的CSP是否具有干细胞特性。3.探讨移植体外扩增CSP细胞在梗死心肌重建中的作用。
方法:1.采用多次胰酶消化法从SD新生大鼠心脏制备心肌细胞悬液,通过流式细胞分选分离获取CSP细胞。用DMEM+10%FBS培养CSP细胞;通过RT-PCR检测Bcrpl、c-kit、MDR1、GATA4、β-MHC等标志,对扩增的CSP细胞进行鉴定;2.采用左冠状动脉前降支结扎法建立鼠AM1动物模型,并随机分为两组;细胞移植组即刻移植Dil标记的CSP细胞;对照组不移植CSP细胞。3.分别于建模成功后第3、7、14、28天,进行心脏超声检查及组织取材,组织冰冻切片通过HE染色和免疫荧光染色,观察移植的CSP细胞参与梗死心肌重建的情况。
结果:
1.每10只新生鼠的心脏组织,经分选可获得3—24×10~4个CSP细胞。
2.CSP细胞体外培养,呈小三角形、多角形、圆形、半圆形或不规则形等贴壁生长,增殖活跃;CSP细胞反复传代培养后,仍具有很强的增殖能力。
3.RT-PCR检测结果显示:原代CSP细胞表达Bcrp1和MDR1,低表达c-Kit,不表达GATA4和β-MHC。体外扩增的CSP细胞随着培养时间的延长和传代次数的增加,逐渐表达心肌标志心肌早期转录因子GATA4和成熟标志β-MHC,但同时持续高表达c-Kit和MDR1,而Bcrp1在逐渐减弱或消失。
4.心脏超声检测:细胞移植组第28天的LVEF值(LVEF:71.1833±13.17553%)与对照组第28天的LVEF值(LVEF:46.2600±14.53801%)相比,统计学分析显示两者差异有统计学意义(P＜0.05)。
5.组织学观察:冰冻切片HE染色光镜观察显示:各标本均出现左室前壁心肌坏死区,心梗区室壁变薄.证实心梗建模成功。免疫荧光共聚焦显微镜观察发现在CSP细胞移植后第7、14、28天,在各心梗区内及周围均发现有Dil标记的CSP细胞嵌入并表达心肌早期标志GATA4和成熟标志MHC。
结论:
1.CSP细胞能够在体外扩增培养并反复传代,且传代CSP细胞仍具有很强的增殖能力。
2.扩增的CSP细胞随着传代培养的时间延长,逐渐向心肌细胞分化,但仍具有心肌干细胞特性。
3.扩增的CSP细胞在体内能够向心肌细胞分化,参与梗死心肌的再生修复。
4.扩增的CSP细胞心梗移植后能有效提高左室射血分数,改善心功能。
Background:In recent years,the people has taked most attentions to the side population cells which are a group of cells from adult stem cells.It was the first time to be found in bone marrow by Goodell's and was called as side population cells in 1996.Now,Side population cells have been shown to exist in various types of adult tissue.Cardiac side population cells(CSP_s) isolated from heart can differentiate into cardiac myocytes by co-cultured with the myocardial cells in vitro.It's also to be identificated that CSP_s can differentiate into cardiac-like cells after being transplantated in vivo and involved in repair of myocardial injury.However,it is unable to meet the needs of clinical treatment because the quantitys of CSP_s is fewer in adult heart tissue.Therefore,it is necessary to further explored that CSP_s have the potential of amplification after being cultured in vitro,and the ability in reparation of myocardial injury.
Objective:1.To observe whether the CSP_s have the potential of amplification after being cultured in vitro.2.To investigate whether the amplified CSP_s have the property of stem cell.3.To investigate the treatment effects of the transplantation of CSP_s in the early myocardial infarction remodeling.
Methods:1.The suspension of myocardial cell was prepared by digested on times with trypsin from postnatal rat hearts,and then CSP_s were sorted out from the suspension by fluorescence-activated cell sorting based on the ability to efflux Hoechst 33342 dye.And CSP_s were cultured in vitro by using DMEM +10%FBS. 2.The expression of Bcrp1、c-kit、MDR1、GATA4 andβ-MHC in cultured CSP_s were detected by RT-PCR.3.Adult rat myocardial infarct model was set up by ligation of left Anterior descending coronary artery after breast- opening,and CSP_s labeled by using CM-DiI were transplanted into the periphery and central of infracting myocardium in experimental rat respectively and were not transplanted in control rat.4.To evaluated the cardiac function Echocardiography exams were performed respectively at 3、7、14and 28day after surgery operation.5.HE stain of the cardiac frozen sections were performed to evaluate the myocardial infaction.To survey differentiation of labeled CSP_s into myocardial cell by confocal microscopy,immunofluorescence stain of GATA4 and MHC were performed in the cardiac frozen sections.
Result:1.3-24×10~4 CSPs were sorted out from 10 neonatal rat heart tissue by fluorescence-activated cell sorting.
2.cultured CSPs adherently grew as a small triangle,polygon,round, semi-circular or irregular-shaped,and showed a strong proliferative capacity.
3.RT-PCR test results show that:the uncultured CSP_s expressed Bcrp1 and MDR1 and did not express GATA4 and bata-MHC.C-kit was poorly or not expressed,cultured CSPs gradually express c-kit,GATA4 and bata-MHC,and meanwhile remain to express Bcrp1 and MDR1.
4.echocardiography detection showed that CSPs transplantation can elevate the left ventricular ejection fraction and improve cardiac function.Compared with the control group(LVEF:46.2600±14.53801%),LVEF of the cell transplantation group(LVEF:71.1833±13.17553%) increased on 28th day(P＜0.05).
5.Myocardial necrosis of left ventricular anterior wall and thinning myocardial wall confirmed the success of myocardial infarction model.Labeled cells expressing GATA4 and MHC were found in the region of myocardial infarction and its periphery on the 7th,14th and 28th day after implanting CSPs labeled CM-DiI.
Conclusion:
1.CSPs can proliferate when cultured in vitro and proliferated CSPs remain to possess characteristics of stem cell
2.During culture,CSPs gradually differentiated into myocardial cells,but still remain property of stem cells
3.Proliferated CSPs in vitro can differentiate into cardiac-like cells after being transplantated into heart,participating in the regeneration of infracted myocardium.
4.Proliferated CSPs can elevate the left ventricular ejection fraction and improve cardiac function after being transplantated into heart
SP(side population)细胞是近年来人们关注的一群成体干细胞。1996年Goodell等首先发现于骨髓,并称之为SP细胞(中文称之为边缘群或侧群细胞)。现已发现,SP细胞在成体组织中广泛存在。来源于心脏的SP细胞(CSP)在体外与心肌细胞共培养条件下能向心肌细胞分化。直接回输体内实验也证实CSP细胞能够形成心肌样细胞,参与损伤心肌的修复。然而成体心脏组织中,CSP细胞含量较少,不能满足临床治疗的需要。因此本课题进一步探讨CSP细胞通过体外培养进行扩增的可能性及其扩增细胞参与心肌重建的能力。
目的:1.观察CSP细胞能否体外培养扩增。2.扩增的CSP是否具有干细胞特性。3.探讨移植体外扩增CSP细胞在梗死心肌重建中的作用。
方法:1.采用多次胰酶消化法从SD新生大鼠心脏制备心肌细胞悬液,通过流式细胞分选分离获取CSP细胞。用DMEM+10%FBS培养CSP细胞;通过RT-PCR检测Bcrpl、c-kit、MDR1、GATA4、β-MHC等标志,对扩增的CSP细胞进行鉴定;2.采用左冠状动脉前降支结扎法建立鼠AM1动物模型,并随机分为两组;细胞移植组即刻移植Dil标记的CSP细胞;对照组不移植CSP细胞。3.分别于建模成功后第3、7、14、28天,进行心脏超声检查及组织取材,组织冰冻切片通过HE染色和免疫荧光染色,观察移植的CSP细胞参与梗死心肌重建的情况。
结果:
1.每10只新生鼠的心脏组织,经分选可获得3—24×10~4个CSP细胞。
2.CSP细胞体外培养,呈小三角形、多角形、圆形、半圆形或不规则形等贴壁生长,增殖活跃;CSP细胞反复传代培养后,仍具有很强的增殖能力。
3.RT-PCR检测结果显示:原代CSP细胞表达Bcrp1和MDR1,低表达c-Kit,不表达GATA4和β-MHC。体外扩增的CSP细胞随着培养时间的延长和传代次数的增加,逐渐表达心肌标志心肌早期转录因子GATA4和成熟标志β-MHC,但同时持续高表达c-Kit和MDR1,而Bcrp1在逐渐减弱或消失。
4.心脏超声检测:细胞移植组第28天的LVEF值(LVEF:71.1833±13.17553%)与对照组第28天的LVEF值(LVEF:46.2600±14.53801%)相比,统计学分析显示两者差异有统计学意义(P＜0.05)。
5.组织学观察:冰冻切片HE染色光镜观察显示:各标本均出现左室前壁心肌坏死区,心梗区室壁变薄.证实心梗建模成功。免疫荧光共聚焦显微镜观察发现在CSP细胞移植后第7、14、28天,在各心梗区内及周围均发现有Dil标记的CSP细胞嵌入并表达心肌早期标志GATA4和成熟标志MHC。
结论:
1.CSP细胞能够在体外扩增培养并反复传代,且传代CSP细胞仍具有很强的增殖能力。
2.扩增的CSP细胞随着传代培养的时间延长,逐渐向心肌细胞分化,但仍具有心肌干细胞特性。
3.扩增的CSP细胞在体内能够向心肌细胞分化,参与梗死心肌的再生修复。
4.扩增的CSP细胞心梗移植后能有效提高左室射血分数,改善心功能。
Background:In recent years,the people has taked most attentions to the side population cells which are a group of cells from adult stem cells.It was the first time to be found in bone marrow by Goodell's and was called as side population cells in 1996.Now,Side population cells have been shown to exist in various types of adult tissue.Cardiac side population cells(CSP_s) isolated from heart can differentiate into cardiac myocytes by co-cultured with the myocardial cells in vitro.It's also to be identificated that CSP_s can differentiate into cardiac-like cells after being transplantated in vivo and involved in repair of myocardial injury.However,it is unable to meet the needs of clinical treatment because the quantitys of CSP_s is fewer in adult heart tissue.Therefore,it is necessary to further explored that CSP_s have the potential of amplification after being cultured in vitro,and the ability in reparation of myocardial injury.
Objective:1.To observe whether the CSP_s have the potential of amplification after being cultured in vitro.2.To investigate whether the amplified CSP_s have the property of stem cell.3.To investigate the treatment effects of the transplantation of CSP_s in the early myocardial infarction remodeling.
Methods:1.The suspension of myocardial cell was prepared by digested on times with trypsin from postnatal rat hearts,and then CSP_s were sorted out from the suspension by fluorescence-activated cell sorting based on the ability to efflux Hoechst 33342 dye.And CSP_s were cultured in vitro by using DMEM +10%FBS. 2.The expression of Bcrp1、c-kit、MDR1、GATA4 andβ-MHC in cultured CSP_s were detected by RT-PCR.3.Adult rat myocardial infarct model was set up by ligation of left Anterior descending coronary artery after breast- opening,and CSP_s labeled by using CM-DiI were transplanted into the periphery and central of infracting myocardium in experimental rat respectively and were not transplanted in control rat.4.To evaluated the cardiac function Echocardiography exams were performed respectively at 3、7、14and 28day after surgery operation.5.HE stain of the cardiac frozen sections were performed to evaluate the myocardial infaction.To survey differentiation of labeled CSP_s into myocardial cell by confocal microscopy,immunofluorescence stain of GATA4 and MHC were performed in the cardiac frozen sections.
Result:1.3-24×10~4 CSPs were sorted out from 10 neonatal rat heart tissue by fluorescence-activated cell sorting.
2.cultured CSPs adherently grew as a small triangle,polygon,round, semi-circular or irregular-shaped,and showed a strong proliferative capacity.
3.RT-PCR test results show that:the uncultured CSP_s expressed Bcrp1 and MDR1 and did not express GATA4 and bata-MHC.C-kit was poorly or not expressed,cultured CSPs gradually express c-kit,GATA4 and bata-MHC,and meanwhile remain to express Bcrp1 and MDR1.
4.echocardiography detection showed that CSPs transplantation can elevate the left ventricular ejection fraction and improve cardiac function.Compared with the control group(LVEF:46.2600±14.53801%),LVEF of the cell transplantation group(LVEF:71.1833±13.17553%) increased on 28th day(P＜0.05).
5.Myocardial necrosis of left ventricular anterior wall and thinning myocardial wall confirmed the success of myocardial infarction model.Labeled cells expressing GATA4 and MHC were found in the region of myocardial infarction and its periphery on the 7th,14th and 28th day after implanting CSPs labeled CM-DiI.
Conclusion:
1.CSPs can proliferate when cultured in vitro and proliferated CSPs remain to possess characteristics of stem cell
2.During culture,CSPs gradually differentiated into myocardial cells,but still remain property of stem cells
3.Proliferated CSPs in vitro can differentiate into cardiac-like cells after being transplantated into heart,participating in the regeneration of infracted myocardium.
4.Proliferated CSPs can elevate the left ventricular ejection fraction and improve cardiac function after being transplantated into heart
引文
1. Ameriean Heart Assoeiation.Heart and Stroke Statistieal Update.Dallas:Ameriean HeartAssoeiation, 1999.
2. Ballard JC, Wood LL, Lansing AM.Transmyoeardial revasculari zation:eriteria for selecting patients, treatmeni, andnursingcare.CritCareNurs, 1997:17:42-49.
3. Kantor B, MeKenna CJ, Caceitolo JA, etal.Transmyoeardial and pereutaneous myoeardial revascularization:current and future role in the treatment of coronary artery disease .Mayo Clin Proe, 1999:74:585 — 592.
4. Bel A, Messas E, Agbulut O, etal.Transplantation of autologous fresh bone marrow into infracted myoeardium:a word of caution.Cireulation ,2003;108:247-252.
5. Anversa P, Nadal,Ginard B.Myocyte renewal and ventrieular remodeling.Nature,2002;41:240-243.
6. Sutton MG,Sharpe N.Left ventrivular remodeling after myoeardial infarction:Pathophysiology and therapy.Cireulation, 2000;101:2981-2988
7. Quaini F,Urbanek K, Beltrami AP,etal.Chimeris of the transplanted heart.N EnglJMed, 2002;346:5-15.
8. LeorJ, Patterson M, Quinines MJ, etal.TransPlantation of fetal myoeardial tissue into infracted myoeardium of rat:a potential method for repair of infracted myocardium?Circulation, 1996;94(suppl II ):332-336.
9. Beltrami AP, Urbanek K, Kajtura J, et al.Evidence that human cardiac myoeytes divide after myocardial infaretion.N Engl J Med.2001, 344(23): 1750-1757.
10. BeltramiAP,BarlucchiL, Torella D, et al. Adult cardiac stem cells are multipotent and supportmyocardial regeneration[ J ]. Cell, 2003, 114(6) : 763-776.
11. Brazekon TR, Rossi FM, Kesher Gl, et al.From bone marrow to brain:expression neuronal phenotypes in adult mice.Seienee, 2000;290:1775-1779.
12. Kehat L Kenyagin-Karsenti D, Snir M, et al.Human embryonic stem cells Differentiate into myoeytes with structural and functional properties cardiomyoeytes.J Clin Invest, 2001;108:407-414.
13. Orkin SH, Zon Ll.HematoPoiesis and stem cells:Plasticity versus development heterogeneity.Nat Immunol, 2002:3:323-328.
14. Siminiak T, Grygielska B, Jerzykowska O, et al.Autologous bone marrow stem cell transplantation in acute myocardial infarction -reporton two cases.Kardiol Pol;2003:59:502-510.
15. Stamm C, Westphal B, Kleine HD, et al.Autologous bone-marrow stem cell Transplantation for myoeardial regeneration.Lancet, 2003:361:45-46.
16. Carter JE and Sehuehlnan EH.Mesenchymal stem cell therapy for neurode-generative disease.NetirobiolAging, 2000;21:152.
17. Broudy VC.Stem cell factor and hematopoiesis.Blood, 1997;90:1345-1364.
18. Oswald J,Boxberger S,Jorgensen,B,et al. Mesenchymal stem cells can be differentiated into endothelial cells invitro.StemCells, 2004;22:377-384.
19. Toma C, Pittenger MF, Cahill KS, et al.Human mesenchymal stem cells differentiate to a cardiomyoeyte phenotype in the adult murine heart.Circulation,2002;10:93-98.
20. Kim DK, Fujiki Y, Fukushima T, et al.Comparison of hematopoietic activities of human bonemarrow and umbilieal cord blood CD34positive and negativecells;Stem Cells, 1999, 17:286-294.
21. Laflamme MA, Myerson D, Saffitz JE, et al.Evidence for cardiomyoeyte Repopulation by extracardiac progenitors in transplanted human hearts.Circ Res; 2002;90:634-640.
22. Kamihata H ,Mat subara H ,Nishiue T ,et al. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblast s , angiogenic ligands ,and cytokines. Circulation ,2001 ,104 :1 046-1 052.
23. Kudo M, Wang Y, Wani MA, Xu M, Ayub A, Ashraf M. Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart. J Mol Cell Cardiol 35:1113-1119, 2003.
24.Matsuura K, Nagai T, Nishigaki N,et al; Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384-11391, 2004.
25 Cornel Badorff,Ralf E Brandes;et al;Transdifferentiation of Blood-Derived Human Adult Endothelial Progenitor Cells Into Functionally Active Cardiomyocytes;Circulation,Feb 2003;107:1024-1032
26.Makino S,Fukuda K,Miyoshi S,et al.Cardiomyocytes can be generated from marrow stromal cells in vitro(J).J Clin Inves,1999,103(5):697-705.
27.Fukuda K;Molecular characterization of regenerated cardiomyocytes derived from adult mesenchymal stem cells(J).Congenit Anom Kyoto,2002,42(1),1-9.
28.Wang JS,Shum-Tim D,Galipeau J,et al.Marrow stromal cells for cellular cardiomyoplasty:feasibility and potential clinical advantages.J Thorac Cardiovasc Surg,2000,120(5),999-1005.
29.Deb A,Wang S,Skelding KA,et al.Bone marrow-derived cardiomyoeytes are present in adult human heart:a study of gender-mismatched bone marrow transplantation patients.Circulation,2003:107:1247-1249.
30.Jackson KA,Majka SM,Wang H,et al.Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells.J Clin Invest,2001:107:1395-1402.
31.Jesu's Herrerosa,Felipe Pro'sperb;et al:Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction European Heart Journal(2003) 24,2012-2020
32.Cornel Badorff,Ralf P.Brandes;et ai;Transdifferentiation of Blood-Derived Human Adult Endothelial Progenitor Cells Into Functionally Active Cardiomyocytes;Circulation,Feb 2003;107:1024-1032
33.夏菁,陈光辉,刘宏斌,等.成人脂肪间充质干细胞体外诱导分化为心肌细的实验研究[J].中国康复理论与实践,2006,12(9):783-784.
34.Gwak S J,Bhang SH,Yang HS et al;In vitro cardiomyogenic differentiation of adipose-derived stromal ceils using transforming growth factor-betal.Cell Biochem Funct.2009 Apr;27(3):148-54
35.Jihyun Yoon,Seung-Cheol Choi,Chi-Yeon Park,et al;Bone Marrow-derived Side Population Cells are Capable of Functional Cardiomyogenic Differentiation;Mol.Cells,2008;.25(2),216-223
36. Chou SM, Nonaka I. Satellite cells and muscle regeneration in diseased human skeletal muscles. J Neurol Sci 34:131-145,1977.
37 Marelli D, Ma F, Chiu RC. Satellite cell implantation for neomyocardial regeneration. Transplant Proc 1992,24:2995,.
38. Taylor DA, Atkins BZ, Hungspreugs P, et al; Regenerating functional myocardium: improved performance after skeletal myoblast transplantation.Nat Med 4:929-933, 1998.
39. Robinson SW, Cho PC, Levitsky H I, et al. Arterial delivery of genetically labeled skeletal myoblasts to the murine heart: Iong2term survival and phenotypic modification of imp lanted myoblasts[ J ]. Cell Transp lant, 1996, 5: 77-91.
40. Atkins BZ; Results of cellular therapy for ischemic myocardial dysfunction. A review.Minerva Cardioangiol. 2002 Aug;50(4):333-341
41. Atkins BZ, Hueman MT, Meuchel J,et al; Cellular cardiomyoplasty improves diastolic properties of injured heart. J Surg Res 85:234-242, 1999.
42. Taylor DA, Atkins BZ, Hungspreugs P,et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4:929-933, 1998.
43. Murry CE, Wiseman RW, Schwartz SM,et al. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest 98:2512-2523, 1996.
44. Leobon B, Garcin I, Menasche P, et al. Myoblasts transplanted into rat infracted myocardium are functionally isolated from their host. Proc Natl Acad Sci U S A 100:7808-7811,
45. Jianhua Zhang, Gisela F. Wilson, Andrew G.et al; Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells; Circ Res.2009;104:e30-e41.
46. Goodell MA, Brose K, Paradis G et al.Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Expl Med 1996;183: 1797-1806.
47 . Atsushi Asakura and Michael A. Rudnicki; Side population cells from diverse adult tissues are capable of in vitro hematopoielic differentiation ;Experimental Hematology 30 (2002) 1339-1345
48. K. Liadakia,b,c, A.T. Khoc,d,e, D. Sanoudou;et al;Side Population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers; Experimental Cell Research 303 (2005) 360- 374
49. Kalindi Parmar, Calies Sauk-Schubert,et al; Sca~+CD34~-murine side population cells are highly enriched for primitive stem cells; Experimental Hematology 31(2003) 244-250
50. Sherrif F. Ibrahim, Alan H. Diercks; Kinetic analyses as a critical parameter in defining the side population (SP) phenotype; Experimental cell research ,2007,313, 1921-1926
51. Jackson, K.A., Majka, S.M., Wang, H., et al ;Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin.Invest. 2001,107,1395-1402.
52. Jihyun Yoon, Seung-Cheol Choi, Chi-Yeon Park,et al; Bone Marrow-derived Side Population Cells are Capable of Functional Cardiomyogenic Differentiation ;Mol. Cells, 2008;. 25( 2), 216-223
53. Hierlihy, A.M., P. Seale, C.G. Lobe,et al, The post-natal heart contains a myocardial stem cell population. FEBS,Lett. 2002, 530:239-243.
54. Martin, C.M., A.P. Meeson, S.M. Robertson, et al;. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifi es cardiac SP cells in the developing and adult heart. Dev. Biol. 2004, 265:262-275.
55. Pfi ster, O., F. Mouquet, M. Jain, R. Summer, et al. CD31- but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation.Circ.Res. 2005,97:52-61.
56. Tomomi Oyama, Toshio Nagai, Hiroshi Wada,et al ; Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo; The Journal of Cell Biology, Vol. 176, No. 3, January 29, 2007 329-341
57. Yano S, Ito Y, Fujimoto M, Hamazaki TS, et al;Characterization and localization of side population cells in mouse skin. Stem Cells 2005;23:834-41
58. Laugwitz KL, Moretti A, Lam J, Gruber P, et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages[J]. Nature,2005,433(7026):647-653.
59. Kalindi Parmar, Calies Sauk-Schubert,et al; Sca~+CD34~-murine side population cells are highly enriched for primitive stem cells; Experimental Hematology 31(2003)244-250
60. Molly A. Harris, Hyuna Yang, Benjamin E;et alCancer Stem Cells Are Enriched in the Side Population Cells in a Mouse Model of Glioma; Cancer Res., Dec 2008; 68: 10051- 10059.
61. Katja Engelmann, Hongmei Shen, and Olivera J. Finn; MCF7 Side Population Cells with Characteristics of Cancer Stem/Progenitor Cells Express the Tumor Antigen MUCl;Cancer Res., Apr 2008; 68: 2419 - 2426.
62. Zhou S, Morris JJ, Barnes Y;et al; Bcrpl gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci U S A. 2002Sep 17;99(19):12339-12344.
63 Zhou S, Schuetz JD, Bunting KD,et al; The ABC transporter Bcrpl/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype; Nat Med. 2001 Sep;7(9):1028-1034.
64. Kim M, Turnquist H, Jackson J,et al; The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res. 2002 Jan;8(1):22-28.
65 Zhou S, Zong Y, Lu T, Sorrentino BP. Hematopoietic cells from mice that are deficient in both Bcrpl/Abcg2 and Mdr1a/1b develop normally but are sensitized to mitoxantrone; Biotechniques. 2003 Dec;35(6):1248-1252.
66. Jafarzadeh A,Esmaeeli-Nadimi A, et al;Serum levels of interleukin (IL)-13,IL-17 and IL-18 in patients with ischemic heart disease. Anadolu Kardiyol Derg.2009 Apr;9(2):75-83
67. SakrarS, VellaichmayE, YoungD, etal.Influence of cytokines and growth factors in ANGII-mediated collagen upregulation by fibroblasts in rats:role of myocytes.AmJPhysiolHeartCircPhysiol,2004,287(1):H107-117.
68 PinskyDJ,CaiB,,YangX,etal.The lethtal effects ofcytokine-induced nitric oxide on cardiac myoeytes are blocked by nitric oxide synthase antagonism or transforming growth factor beta.JClinlnvest,1995,95(2):677-685.
69.Holmes JW,Borg TkandCovell JW.Structure and meehanics of healing myoeardial infarcts,[J].AnnuRevBiomedEng2005;7,223-253.
70.AicherA,B rennerW,ZuhayraM,et al.Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling;[J].Circulation,2003,107(16):2134-2139.
71.Wang JS,Shum-Tim D,Galipeau J,et al.Marrow stromal cells for cellular cardiomyoplasty:feasibility and potential clinical advantages[J].Thorac Cardiovasc Surg,2090,120(5):999-1005.
72.Taylor DA,Atkins BZ,Hungspreugs P,et al;Regenerating functional myocardium:improved performance after skeletal myoblast transplantation.Nat Med 4:929-933,1998.
1.JoannaE.Grove,et al;Plasticity of bone marrow-derived stem cells;stem cells;2004;22:487-500
2.姚鹏:干细胞在肝脏疾病治疗中的应用;医学研究杂志;2007.36(6).8-10
3.AntonioEBeltrami;DanielCesselli;Natascha Bergamin etc;Multipotent cells can be generated in vitro from several adult humam organs(heat.liver.bone marrow);Blood;2007;110:3438-3446.
4.MASAHIRO MIYAZAKI,a,d MARHAEN HARDJO,,et al;,Isolation of a Bone Marrow-Derived Stem Cell Line with High Proliferation Potential and Its Application for Preventing Acute Fatal Liver Failure;STEM CELLS 2007;25:2855-2863
5.B.E.Petersen,et al;Bone Marro\v as a Potential Source of Hepatic Oval Cells;Science;284,1168(1999);
6.Seh-Hoon Oh,~* Masahiro Miyazaki,et al;,Hepatocyte Growth Factor Induces Differentiation of Adult Rat Bone Marrow Ceils into a Hepatocyte Lineage in Vitro Biochemical and Biophysical Research Communications 279,590-504(2000)
7.Eric Lagasse,Heather Connors,MuhsenAl-Dhaalimy,et al;Purified hematopoietic stem cells can differentiate into hepatocytes in vivo Nature medicine.2000.6(11),1229-1234
8.Yoon-Young Jang,Michael I.Collector,et al;Hematopoietic stem cells convert into liver ceilswithin days without fusion;Nature cell biology 2004,6(6) 532-539
9.Y.Zhan,Y.Wang,L.Wei,et al;Differentiation of Hematopoietic Stem Cells into Hepatocytes in Liver Fibrosis in Rats Transplantation Proceedings,2006,38,3082-3085
10.Xin Wng,Holger Willenbring,et al;Cell fusion is the principal source of bone-marrow-derived hepatocytes;Nature;Apr 24,2003;422,6934;Health &Medical Complete
11.Robert E.Schwartz,Morayma Reyes,Lisa Koodie,et al;Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like
12.Kuan-Der Lee,Tom Kwang-Chun Kuo,In Vitro Hepatic Differentiation of Human Mesenchymal Stem Cells;Hepatology,2004;40:1275-1284.
13 John MLuk,P.Ping Wang,Carol K.Lee,et al;Hepatic potential of bone marrow stromal cells:Development of in vitro co-culture and intra-portal transplantation models;Journal of Immunological Methods 305(2005) 39-47
14.Shin-Yeu Onga,Hui Daia,Kam W.Leong;Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture;Biomaterials 27(2006)4087-4097
15.Zhang Qihao,Chen XiGu,Cui GuangHui et al;Spheroid Formation and Differentiation into Hepatocyte-Like Cells of Rat Mesenchymal Stem Cell Induced by Co-Culture with Liver Cells;DNA AND CELL BIOLOGY;Volume 26,Number 7;2007;497-503
16.Zunfu Ke,Feng Zhou,Liantang Wang;et al;Down-regulation of Wnt signaling could promote bone marrow-derived mesenchymal stem cells to differentiate into hepatocytes Biochemical and Biophysical Research Communications 2008,367,342-348
17.Xiao-Lei Shi,Yu-Dong Qiu,Xin-Yu Wu,et al;In vitro differentiation of mouse bone marrow mononuclearcells into hepatocyte-like cells;Hepatology Research,2005,31,223-231
18.Jan Schulte am Esch,II,Wolfram Trudo Knoefel,et a!;Portal Application of Autoiogous CD133+ Bone Marrow Ceils to the Liver:A Novel Concept to Support Hepatic Regeneration;Stem Cells 2005;23;463-470
19.Avital l,lnderbitzin D.Isolation,characterization and transplantation of bone marrow-derived hepatocyte stem cells.Biochem Biophys Res Commun 2001;288(1):156-164
20.展玉涛;魏来;陈红松等;骨髓干细胞在大鼠肝纤维化形成环境中的分化;中华肝脏病杂志:2003,11(11),673-675
21.YamamotoN,TeraiS,OhataS;et al;A subpopulation of bone marrow cells depleted by a novel antibody,anti-liv8,is useful for cell therapy to repair damaged liver;[J],Biochem biophys Res Com,2004,313(4):1110-1118
22.Gue' nahel H. Danet*, Jennifer L. Luongo(?),et al;ClqRp defines a new human stem cell populationwith hematopoietic and hepatic potential PNAS. August 6,20021. 99(16) ,10441-10445
23 .Goodell MA, Brose K, Paradis G et al.Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Expl Med 1996;183: 1797-1806.
24 .Atsushi Asakura and Michael A. Rudnicki; Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation ;Experimental Hematology 30(2002) 1339-1345
25. K. Liadakia,b,c, A.T. Khoc,d,e, D. Sanoudou;et al;Side Population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers; Experimental Cell Research 303 (2005) 360- 374
26. Kalindi Parmar, Calies Sauk-Schubert,et al; Sca~+CD34~-inurine side population cells are highly enriched for primitive stem cells; Experimental Hematology 31(2003) 244-250
27. Sherrif F. Ibrahim, Alan H. Diercks; Kinetic analyses as a critical parameter in defining the side population (SP) phenotype; Experimental cell research 3 13(2007)1921-1926
28. Daniel J. Pearce, Christopher M. Ridler, et al; Multiparameter analysis of murine bone marrow side popuiationcells;Blood.2004;103:2541-2546
29. Christelle Rochona, Vincent Frouina, Sylvie Bortolia,et al;Comparison of gene expression pattern in SP cell populations from four tissues to define common"sternness functions"Experimental cell research 312(2006)2074-2082
30. Gerald G.Wulf,Kang-Li Luo,et al;Cells of the hepatic side population contribute to liver regeneration and can be replenished by bone marrow stem cells;Haematologica.2003;88:368-378
31. Xiaodan Ren, Cory Hogaboam, Audra Carpenter,et al;Stem cell factor restores hepatocyte proliferationin IL-6 knockout mice following 70% hepatectomyJ. Clin.Invest. 112:1407-1418(2003).
32.Yukiko Saji,Shinji Tamura,Yuichi Yoshida,et al;Basic fibroblast growth factor promotes the trans-differentiation of mouse bone marrow cells into hepatic lineage cells via multiple liver-enriched transcription factors;Journal of Hepatology 41(2004) 545-550
33.Zamegar,R.,and Michalopoulos,G.K.(1995) The many faces of hepatocyte growth factor:From hepatopoiesis to hematopoiesis.J.Cell Biol.129,1177-1180.
34.Rubin,J.S.,Bottaro,D.P.,and Aaronson,S.A.(1993) Hepatocyte growth factor/scatter factor and its receptor,the c-met proto-oncogene product.Biochim.Biophys.Acta 1155,357-371.
35.Seh-Hoon Oh,~* Masahiro Miyazaki,et al;Hepatocyte Growth Factor Induces Differentiation of Adult Rat Bone Marrow Cells into a Hepatocyte Lineage in Vitro;Biochemical and Biophysical Research Communications 279,500-504(2000)
36.Gennady P./lyin,Denise Glaise,David Gilot,et al;Regulation and role of p21 and p27 cyclin-dependent kinase inhibitors during hepatocyte differentiation and growth Am J Physiol Gastrointest Liver Physiol 285:G115-G127,2003.
37.Giancarlo Forte,Marilena Minieri,et al;Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells:Proliferation,Migration,and Differentiation;Stem Cells 2006;24;23-33;
38.司煜安,许文荣,严永敏等:体外诱导人骨髓问质干细胞分化为肝细胞样细胞;江苏大学学报(医学版),2008,18(1),6-10
39.Sarah Snykers,Tamara Vanhaecke,et al;Peggy Papeleu,Sequential Exposure to Cytokines Reflecting Embryogenesis:The Key for in vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-like Cells;Toxicological Scinces;2006;94(2),330-341
40.Zoran Ilic,Hyam Leffert,,et al;Sequential Exposure to Cytokines Reflecting Embryogenesis:The Key for In Vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-Like Cells;Toxicological Scinces 94(2),235-239(2006)
41.Theise ND.Gastrointestinal stem cells.III.Emergent themes of liver stem cell biology:niche,quies2 cence,self2renewal,and plasticity[J]Am J Physiol Gastrointest Liver Physiol,2 0 0 6,2 9 0(2 ):G1 8 9-1 9 3.
42.Hynda K Kleinman_,Deborah Philp and Matthew P Hoffman,Role of the extracellular matrix in morphogenesis;Biotechnology:2003,14:526-53
43.Atsushi Suzuki,Atsushi Iwama,Hitoshi Miyashita,et al;Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells;Development anddisease;2003,130,2513-2524
44.周播江,钟翠平,顾云娣等:肝再生大鼠血清诱导骨髓干细胞向肝细胞分化的试验研究;中华肝病杂志;2004,12,730-733
45.李伟,刘苏南,罗端德等;胆汁化血清对骨髓间充质干细胞向肝细胞样细胞定向分化的诱导内科理论与实践:2007年第2卷第4期;260.264
46.Yasuhiro Yamadaa,Eishi Nishirnotoa,Hiroaki Mitsuya;et al;In vitro transdifferentiation of adult bone marrow Sca-1~+ cKit~+ cells cocultured with fetal liver cells into hepatic-like cells without fusion;Experimental Hematology 34(2006) 97-106
47.Meijing Wang,1 Paul R.Crisostomo,1 Christine Herring,et al Human progenitor cells from bone marrow or adipose tissue produce VEGF,HGF,and IGF-I in response to TNF by a p38 MAPK-dependent mechanism;Am J PhysioI Regul Integr Comp Physiol 291:R880-R884,2006.
48.Kazuo Okumoto,Takafumi Saito~*,Etsuko Hattori,et al;Differentiation of rat bone marrow cells cultured on artificial basement membrane containing extracellular matrix into a liver cell lineage Journal of Hepatology 2005,43,110-116
49.Shintaro Yamazaki,Kenji Miki,Tadatoshi Takayama;et al Hepatic gene induction in murine bone marrow after hepatectomy;Journal of Hepatology 44(2006)325-333
50.Kristin M.Braun,Anne W.et el;Hepatic Microenvironment Affects Oval Cell Localization in Albumin-Urokinase-Type Plasminogen Activator Transgenic Mice;Am J Pathol 2003,162:195-202
51. Roberto M. Lemoli, Francesco Bertolini, Ranieri Cancedda, et al; Stem cell plasticity: time for a reappraisal? Haematologica 2005; 90:360-381
52. Yoshitaka Sato, Katsuhide Miyake, et al; Sumoylation of CCAAT/Enhancer-binding Protein _ and Its Functional Roles in Hepatocyte Differentiation;The Journal of Biological Chemistry; 2006.281(31), .21629-21639
53. Xin Wng,Holger Willenbring,et al;Cell fusion is the principal source of bone-marrow-derived hepatocytes; Nature; Apr 24, 2003; 422, 6934; Health & Medical Complete
54. Carla Boccaccio*, Margherita Ando*, and Paolo M. Comoglio;et al; A differentiation switch for genetically modified hepatocytes; The FASEB Journal express article 10.1096/fj.01-0537fje.
55. Laura Erker , Markus ;Grompe; Signaling networks in hepatic oval cell activarionStem Cell Research 2008.10.1016/j.scr.2008.01.002
56. Jason K. Sicklick,Yin-Xiong ,et al;Hedgehog signaling maintains resident hepatic progenitors throughout life; Am J Physiol Gastrointest Liver Physiol 290:G859-G870, 2006
57. Sunny Z. Hussain,a Tamara Sneddon,et al; Wnt impacts growth and differentiation in ex vivo liver development ;Experimental Cell Research 292(2004) 157- 169
58 .Kazuo Okumoto, Takafumi Saito, Etsuko Hattori,et al; Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation;Biochemical and Biophysical Research Communications 304 (2003) 691-695
59. Jixuan Li, Gang Ning, and Stephen A. Duncan; Mammalian hepatocyte differentiation requires the transcription factor HNF-4a;Genes &Development;2000 14:464-474
60. Jean-Bernard Beaudry,l Christophe E.Threshold Levels of Hepatocyte Nuclear Factor 6 (HNF-6) Acting in Synergy with HNF-4 and PGC-1_ Are Required for Time-Specific Gene Expression during Liver Development ; Molecular and cellular biology , Aug. 2006, p. 6037-6046
61. Xavier Prieur, Frank G. Schaap, Herve' Coste;et al; Hepatocyte Nuclear Factor-4_Regulates the Human Apolipoprotein AV Gene: Identification of a Novel Response Element and Involvement in the Control by Peroxisome Proliferator-Activated Receptor-_Coactivator-1_, AMP-Activated Protein Kinase,and Mitogen-Activated Protein Kinase Pathway; Molecular Endocrinology,2005,19(12):3107-3125
62. Celia P. Marti'nez-Jime' nez, Jose' V. Castell, M.et al; Transcriptional Activation of CYP2C9, CYP1A1, and CYP1A2 by Hepatocyte Nuclear Factor 4_ Requires Coactivators Peroxisomal Proliferator Activated Receptor-_ Coactivator 1_and Steroid Receptor Coactivator 1; Mol Pharmacol 70:1681-1692,( 2006)
63. Grahamp.hayhurst,Ying-Hue Lee,et al; Hepatocyte Nuclear Factor 4a (Nuclear Receptor 2Al)Is Essential for Maintenance of Hepatic Gene Expression and Lipid Homeostasis;Molecular and cellular Biologr,Feb.2001.21(4)1393-1403
64. Uzma Samadani and Robert H. Costa; The Transcriptional Activator Hepatocyte Nuclear Factor 6 Regulates Liver Gene Expression; Molecular and cellular biology, Nov. 1996, p. 6273-6284
65. Irene Kynnizi, Pantelis Hatzis, Nitsa Katrakili,et al; Plasticity and expanding complexity of the hepatic transcription factor network during liver development;Genes & Dev. 2006 20: 2293-2305
66. P. Stock, M.S. Staege, L.P. M(?)ller, Hepatocytes Derived From Adult Stem Cells ; Transplantation Proceedings, 2008, 40, 620-623
67. Jai-lin Zhang,Jin Cai,John D,et al;Long-Term Transgene Expression and Survival ofTransgene-Expressing Grafts Following LentivirusTransduction of Bone Marrow Side Population Cells; Transplantation 2005;79: 882-888
68. Anuradha Menthena, Niloyjyoti Deb,et al;Bone Marrow Progenitors Are Not the Source of Expanding Oval Cells in Injured Liver; Stem Cells 2004;22;1049-1061
69. Felix C. Popp, Przemyslaw Slowik,et al;No Contribution of Multipotent Mesenchymal Stromal Cells to Liver Regeneration in a Rat Model of Prolonged Hepatic In(?)ury;Stem Cells 2007;25;639-645;
70.Lorenzo Valfre di Bonzo,Ivana Ferrero,Carlo Cravanzola et al;Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine:Engraftment and hepatocyte differentiation versus profibrogenic potential;Gut,Jul 2007;10.1136/gut.2006.111617.
2. Ballard JC, Wood LL, Lansing AM.Transmyoeardial revasculari zation:eriteria for selecting patients, treatmeni, andnursingcare.CritCareNurs, 1997:17:42-49.
3. Kantor B, MeKenna CJ, Caceitolo JA, etal.Transmyoeardial and pereutaneous myoeardial revascularization:current and future role in the treatment of coronary artery disease .Mayo Clin Proe, 1999:74:585 — 592.
4. Bel A, Messas E, Agbulut O, etal.Transplantation of autologous fresh bone marrow into infracted myoeardium:a word of caution.Cireulation ,2003;108:247-252.
5. Anversa P, Nadal,Ginard B.Myocyte renewal and ventrieular remodeling.Nature,2002;41:240-243.
6. Sutton MG,Sharpe N.Left ventrivular remodeling after myoeardial infarction:Pathophysiology and therapy.Cireulation, 2000;101:2981-2988
7. Quaini F,Urbanek K, Beltrami AP,etal.Chimeris of the transplanted heart.N EnglJMed, 2002;346:5-15.
8. LeorJ, Patterson M, Quinines MJ, etal.TransPlantation of fetal myoeardial tissue into infracted myoeardium of rat:a potential method for repair of infracted myocardium?Circulation, 1996;94(suppl II ):332-336.
9. Beltrami AP, Urbanek K, Kajtura J, et al.Evidence that human cardiac myoeytes divide after myocardial infaretion.N Engl J Med.2001, 344(23): 1750-1757.
10. BeltramiAP,BarlucchiL, Torella D, et al. Adult cardiac stem cells are multipotent and supportmyocardial regeneration[ J ]. Cell, 2003, 114(6) : 763-776.
11. Brazekon TR, Rossi FM, Kesher Gl, et al.From bone marrow to brain:expression neuronal phenotypes in adult mice.Seienee, 2000;290:1775-1779.
12. Kehat L Kenyagin-Karsenti D, Snir M, et al.Human embryonic stem cells Differentiate into myoeytes with structural and functional properties cardiomyoeytes.J Clin Invest, 2001;108:407-414.
13. Orkin SH, Zon Ll.HematoPoiesis and stem cells:Plasticity versus development heterogeneity.Nat Immunol, 2002:3:323-328.
14. Siminiak T, Grygielska B, Jerzykowska O, et al.Autologous bone marrow stem cell transplantation in acute myocardial infarction -reporton two cases.Kardiol Pol;2003:59:502-510.
15. Stamm C, Westphal B, Kleine HD, et al.Autologous bone-marrow stem cell Transplantation for myoeardial regeneration.Lancet, 2003:361:45-46.
16. Carter JE and Sehuehlnan EH.Mesenchymal stem cell therapy for neurode-generative disease.NetirobiolAging, 2000;21:152.
17. Broudy VC.Stem cell factor and hematopoiesis.Blood, 1997;90:1345-1364.
18. Oswald J,Boxberger S,Jorgensen,B,et al. Mesenchymal stem cells can be differentiated into endothelial cells invitro.StemCells, 2004;22:377-384.
19. Toma C, Pittenger MF, Cahill KS, et al.Human mesenchymal stem cells differentiate to a cardiomyoeyte phenotype in the adult murine heart.Circulation,2002;10:93-98.
20. Kim DK, Fujiki Y, Fukushima T, et al.Comparison of hematopoietic activities of human bonemarrow and umbilieal cord blood CD34positive and negativecells;Stem Cells, 1999, 17:286-294.
21. Laflamme MA, Myerson D, Saffitz JE, et al.Evidence for cardiomyoeyte Repopulation by extracardiac progenitors in transplanted human hearts.Circ Res; 2002;90:634-640.
22. Kamihata H ,Mat subara H ,Nishiue T ,et al. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblast s , angiogenic ligands ,and cytokines. Circulation ,2001 ,104 :1 046-1 052.
23. Kudo M, Wang Y, Wani MA, Xu M, Ayub A, Ashraf M. Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart. J Mol Cell Cardiol 35:1113-1119, 2003.
24.Matsuura K, Nagai T, Nishigaki N,et al; Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384-11391, 2004.
25 Cornel Badorff,Ralf E Brandes;et al;Transdifferentiation of Blood-Derived Human Adult Endothelial Progenitor Cells Into Functionally Active Cardiomyocytes;Circulation,Feb 2003;107:1024-1032
26.Makino S,Fukuda K,Miyoshi S,et al.Cardiomyocytes can be generated from marrow stromal cells in vitro(J).J Clin Inves,1999,103(5):697-705.
27.Fukuda K;Molecular characterization of regenerated cardiomyocytes derived from adult mesenchymal stem cells(J).Congenit Anom Kyoto,2002,42(1),1-9.
28.Wang JS,Shum-Tim D,Galipeau J,et al.Marrow stromal cells for cellular cardiomyoplasty:feasibility and potential clinical advantages.J Thorac Cardiovasc Surg,2000,120(5),999-1005.
29.Deb A,Wang S,Skelding KA,et al.Bone marrow-derived cardiomyoeytes are present in adult human heart:a study of gender-mismatched bone marrow transplantation patients.Circulation,2003:107:1247-1249.
30.Jackson KA,Majka SM,Wang H,et al.Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells.J Clin Invest,2001:107:1395-1402.
31.Jesu's Herrerosa,Felipe Pro'sperb;et al:Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction European Heart Journal(2003) 24,2012-2020
32.Cornel Badorff,Ralf P.Brandes;et ai;Transdifferentiation of Blood-Derived Human Adult Endothelial Progenitor Cells Into Functionally Active Cardiomyocytes;Circulation,Feb 2003;107:1024-1032
33.夏菁,陈光辉,刘宏斌,等.成人脂肪间充质干细胞体外诱导分化为心肌细的实验研究[J].中国康复理论与实践,2006,12(9):783-784.
34.Gwak S J,Bhang SH,Yang HS et al;In vitro cardiomyogenic differentiation of adipose-derived stromal ceils using transforming growth factor-betal.Cell Biochem Funct.2009 Apr;27(3):148-54
35.Jihyun Yoon,Seung-Cheol Choi,Chi-Yeon Park,et al;Bone Marrow-derived Side Population Cells are Capable of Functional Cardiomyogenic Differentiation;Mol.Cells,2008;.25(2),216-223
36. Chou SM, Nonaka I. Satellite cells and muscle regeneration in diseased human skeletal muscles. J Neurol Sci 34:131-145,1977.
37 Marelli D, Ma F, Chiu RC. Satellite cell implantation for neomyocardial regeneration. Transplant Proc 1992,24:2995,.
38. Taylor DA, Atkins BZ, Hungspreugs P, et al; Regenerating functional myocardium: improved performance after skeletal myoblast transplantation.Nat Med 4:929-933, 1998.
39. Robinson SW, Cho PC, Levitsky H I, et al. Arterial delivery of genetically labeled skeletal myoblasts to the murine heart: Iong2term survival and phenotypic modification of imp lanted myoblasts[ J ]. Cell Transp lant, 1996, 5: 77-91.
40. Atkins BZ; Results of cellular therapy for ischemic myocardial dysfunction. A review.Minerva Cardioangiol. 2002 Aug;50(4):333-341
41. Atkins BZ, Hueman MT, Meuchel J,et al; Cellular cardiomyoplasty improves diastolic properties of injured heart. J Surg Res 85:234-242, 1999.
42. Taylor DA, Atkins BZ, Hungspreugs P,et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4:929-933, 1998.
43. Murry CE, Wiseman RW, Schwartz SM,et al. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest 98:2512-2523, 1996.
44. Leobon B, Garcin I, Menasche P, et al. Myoblasts transplanted into rat infracted myocardium are functionally isolated from their host. Proc Natl Acad Sci U S A 100:7808-7811,
45. Jianhua Zhang, Gisela F. Wilson, Andrew G.et al; Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells; Circ Res.2009;104:e30-e41.
46. Goodell MA, Brose K, Paradis G et al.Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Expl Med 1996;183: 1797-1806.
47 . Atsushi Asakura and Michael A. Rudnicki; Side population cells from diverse adult tissues are capable of in vitro hematopoielic differentiation ;Experimental Hematology 30 (2002) 1339-1345
48. K. Liadakia,b,c, A.T. Khoc,d,e, D. Sanoudou;et al;Side Population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers; Experimental Cell Research 303 (2005) 360- 374
49. Kalindi Parmar, Calies Sauk-Schubert,et al; Sca~+CD34~-murine side population cells are highly enriched for primitive stem cells; Experimental Hematology 31(2003) 244-250
50. Sherrif F. Ibrahim, Alan H. Diercks; Kinetic analyses as a critical parameter in defining the side population (SP) phenotype; Experimental cell research ,2007,313, 1921-1926
51. Jackson, K.A., Majka, S.M., Wang, H., et al ;Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin.Invest. 2001,107,1395-1402.
52. Jihyun Yoon, Seung-Cheol Choi, Chi-Yeon Park,et al; Bone Marrow-derived Side Population Cells are Capable of Functional Cardiomyogenic Differentiation ;Mol. Cells, 2008;. 25( 2), 216-223
53. Hierlihy, A.M., P. Seale, C.G. Lobe,et al, The post-natal heart contains a myocardial stem cell population. FEBS,Lett. 2002, 530:239-243.
54. Martin, C.M., A.P. Meeson, S.M. Robertson, et al;. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifi es cardiac SP cells in the developing and adult heart. Dev. Biol. 2004, 265:262-275.
55. Pfi ster, O., F. Mouquet, M. Jain, R. Summer, et al. CD31- but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation.Circ.Res. 2005,97:52-61.
56. Tomomi Oyama, Toshio Nagai, Hiroshi Wada,et al ; Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo; The Journal of Cell Biology, Vol. 176, No. 3, January 29, 2007 329-341
57. Yano S, Ito Y, Fujimoto M, Hamazaki TS, et al;Characterization and localization of side population cells in mouse skin. Stem Cells 2005;23:834-41
58. Laugwitz KL, Moretti A, Lam J, Gruber P, et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages[J]. Nature,2005,433(7026):647-653.
59. Kalindi Parmar, Calies Sauk-Schubert,et al; Sca~+CD34~-murine side population cells are highly enriched for primitive stem cells; Experimental Hematology 31(2003)244-250
60. Molly A. Harris, Hyuna Yang, Benjamin E;et alCancer Stem Cells Are Enriched in the Side Population Cells in a Mouse Model of Glioma; Cancer Res., Dec 2008; 68: 10051- 10059.
61. Katja Engelmann, Hongmei Shen, and Olivera J. Finn; MCF7 Side Population Cells with Characteristics of Cancer Stem/Progenitor Cells Express the Tumor Antigen MUCl;Cancer Res., Apr 2008; 68: 2419 - 2426.
62. Zhou S, Morris JJ, Barnes Y;et al; Bcrpl gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci U S A. 2002Sep 17;99(19):12339-12344.
63 Zhou S, Schuetz JD, Bunting KD,et al; The ABC transporter Bcrpl/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype; Nat Med. 2001 Sep;7(9):1028-1034.
64. Kim M, Turnquist H, Jackson J,et al; The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res. 2002 Jan;8(1):22-28.
65 Zhou S, Zong Y, Lu T, Sorrentino BP. Hematopoietic cells from mice that are deficient in both Bcrpl/Abcg2 and Mdr1a/1b develop normally but are sensitized to mitoxantrone; Biotechniques. 2003 Dec;35(6):1248-1252.
66. Jafarzadeh A,Esmaeeli-Nadimi A, et al;Serum levels of interleukin (IL)-13,IL-17 and IL-18 in patients with ischemic heart disease. Anadolu Kardiyol Derg.2009 Apr;9(2):75-83
67. SakrarS, VellaichmayE, YoungD, etal.Influence of cytokines and growth factors in ANGII-mediated collagen upregulation by fibroblasts in rats:role of myocytes.AmJPhysiolHeartCircPhysiol,2004,287(1):H107-117.
68 PinskyDJ,CaiB,,YangX,etal.The lethtal effects ofcytokine-induced nitric oxide on cardiac myoeytes are blocked by nitric oxide synthase antagonism or transforming growth factor beta.JClinlnvest,1995,95(2):677-685.
69.Holmes JW,Borg TkandCovell JW.Structure and meehanics of healing myoeardial infarcts,[J].AnnuRevBiomedEng2005;7,223-253.
70.AicherA,B rennerW,ZuhayraM,et al.Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling;[J].Circulation,2003,107(16):2134-2139.
71.Wang JS,Shum-Tim D,Galipeau J,et al.Marrow stromal cells for cellular cardiomyoplasty:feasibility and potential clinical advantages[J].Thorac Cardiovasc Surg,2090,120(5):999-1005.
72.Taylor DA,Atkins BZ,Hungspreugs P,et al;Regenerating functional myocardium:improved performance after skeletal myoblast transplantation.Nat Med 4:929-933,1998.
1.JoannaE.Grove,et al;Plasticity of bone marrow-derived stem cells;stem cells;2004;22:487-500
2.姚鹏:干细胞在肝脏疾病治疗中的应用;医学研究杂志;2007.36(6).8-10
3.AntonioEBeltrami;DanielCesselli;Natascha Bergamin etc;Multipotent cells can be generated in vitro from several adult humam organs(heat.liver.bone marrow);Blood;2007;110:3438-3446.
4.MASAHIRO MIYAZAKI,a,d MARHAEN HARDJO,,et al;,Isolation of a Bone Marrow-Derived Stem Cell Line with High Proliferation Potential and Its Application for Preventing Acute Fatal Liver Failure;STEM CELLS 2007;25:2855-2863
5.B.E.Petersen,et al;Bone Marro\v as a Potential Source of Hepatic Oval Cells;Science;284,1168(1999);
6.Seh-Hoon Oh,~* Masahiro Miyazaki,et al;,Hepatocyte Growth Factor Induces Differentiation of Adult Rat Bone Marrow Ceils into a Hepatocyte Lineage in Vitro Biochemical and Biophysical Research Communications 279,590-504(2000)
7.Eric Lagasse,Heather Connors,MuhsenAl-Dhaalimy,et al;Purified hematopoietic stem cells can differentiate into hepatocytes in vivo Nature medicine.2000.6(11),1229-1234
8.Yoon-Young Jang,Michael I.Collector,et al;Hematopoietic stem cells convert into liver ceilswithin days without fusion;Nature cell biology 2004,6(6) 532-539
9.Y.Zhan,Y.Wang,L.Wei,et al;Differentiation of Hematopoietic Stem Cells into Hepatocytes in Liver Fibrosis in Rats Transplantation Proceedings,2006,38,3082-3085
10.Xin Wng,Holger Willenbring,et al;Cell fusion is the principal source of bone-marrow-derived hepatocytes;Nature;Apr 24,2003;422,6934;Health &Medical Complete
11.Robert E.Schwartz,Morayma Reyes,Lisa Koodie,et al;Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like
12.Kuan-Der Lee,Tom Kwang-Chun Kuo,In Vitro Hepatic Differentiation of Human Mesenchymal Stem Cells;Hepatology,2004;40:1275-1284.
13 John MLuk,P.Ping Wang,Carol K.Lee,et al;Hepatic potential of bone marrow stromal cells:Development of in vitro co-culture and intra-portal transplantation models;Journal of Immunological Methods 305(2005) 39-47
14.Shin-Yeu Onga,Hui Daia,Kam W.Leong;Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture;Biomaterials 27(2006)4087-4097
15.Zhang Qihao,Chen XiGu,Cui GuangHui et al;Spheroid Formation and Differentiation into Hepatocyte-Like Cells of Rat Mesenchymal Stem Cell Induced by Co-Culture with Liver Cells;DNA AND CELL BIOLOGY;Volume 26,Number 7;2007;497-503
16.Zunfu Ke,Feng Zhou,Liantang Wang;et al;Down-regulation of Wnt signaling could promote bone marrow-derived mesenchymal stem cells to differentiate into hepatocytes Biochemical and Biophysical Research Communications 2008,367,342-348
17.Xiao-Lei Shi,Yu-Dong Qiu,Xin-Yu Wu,et al;In vitro differentiation of mouse bone marrow mononuclearcells into hepatocyte-like cells;Hepatology Research,2005,31,223-231
18.Jan Schulte am Esch,II,Wolfram Trudo Knoefel,et a!;Portal Application of Autoiogous CD133+ Bone Marrow Ceils to the Liver:A Novel Concept to Support Hepatic Regeneration;Stem Cells 2005;23;463-470
19.Avital l,lnderbitzin D.Isolation,characterization and transplantation of bone marrow-derived hepatocyte stem cells.Biochem Biophys Res Commun 2001;288(1):156-164
20.展玉涛;魏来;陈红松等;骨髓干细胞在大鼠肝纤维化形成环境中的分化;中华肝脏病杂志:2003,11(11),673-675
21.YamamotoN,TeraiS,OhataS;et al;A subpopulation of bone marrow cells depleted by a novel antibody,anti-liv8,is useful for cell therapy to repair damaged liver;[J],Biochem biophys Res Com,2004,313(4):1110-1118
22.Gue' nahel H. Danet*, Jennifer L. Luongo(?),et al;ClqRp defines a new human stem cell populationwith hematopoietic and hepatic potential PNAS. August 6,20021. 99(16) ,10441-10445
23 .Goodell MA, Brose K, Paradis G et al.Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Expl Med 1996;183: 1797-1806.
24 .Atsushi Asakura and Michael A. Rudnicki; Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation ;Experimental Hematology 30(2002) 1339-1345
25. K. Liadakia,b,c, A.T. Khoc,d,e, D. Sanoudou;et al;Side Population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers; Experimental Cell Research 303 (2005) 360- 374
26. Kalindi Parmar, Calies Sauk-Schubert,et al; Sca~+CD34~-inurine side population cells are highly enriched for primitive stem cells; Experimental Hematology 31(2003) 244-250
27. Sherrif F. Ibrahim, Alan H. Diercks; Kinetic analyses as a critical parameter in defining the side population (SP) phenotype; Experimental cell research 3 13(2007)1921-1926
28. Daniel J. Pearce, Christopher M. Ridler, et al; Multiparameter analysis of murine bone marrow side popuiationcells;Blood.2004;103:2541-2546
29. Christelle Rochona, Vincent Frouina, Sylvie Bortolia,et al;Comparison of gene expression pattern in SP cell populations from four tissues to define common"sternness functions"Experimental cell research 312(2006)2074-2082
30. Gerald G.Wulf,Kang-Li Luo,et al;Cells of the hepatic side population contribute to liver regeneration and can be replenished by bone marrow stem cells;Haematologica.2003;88:368-378
31. Xiaodan Ren, Cory Hogaboam, Audra Carpenter,et al;Stem cell factor restores hepatocyte proliferationin IL-6 knockout mice following 70% hepatectomyJ. Clin.Invest. 112:1407-1418(2003).
32.Yukiko Saji,Shinji Tamura,Yuichi Yoshida,et al;Basic fibroblast growth factor promotes the trans-differentiation of mouse bone marrow cells into hepatic lineage cells via multiple liver-enriched transcription factors;Journal of Hepatology 41(2004) 545-550
33.Zamegar,R.,and Michalopoulos,G.K.(1995) The many faces of hepatocyte growth factor:From hepatopoiesis to hematopoiesis.J.Cell Biol.129,1177-1180.
34.Rubin,J.S.,Bottaro,D.P.,and Aaronson,S.A.(1993) Hepatocyte growth factor/scatter factor and its receptor,the c-met proto-oncogene product.Biochim.Biophys.Acta 1155,357-371.
35.Seh-Hoon Oh,~* Masahiro Miyazaki,et al;Hepatocyte Growth Factor Induces Differentiation of Adult Rat Bone Marrow Cells into a Hepatocyte Lineage in Vitro;Biochemical and Biophysical Research Communications 279,500-504(2000)
36.Gennady P./lyin,Denise Glaise,David Gilot,et al;Regulation and role of p21 and p27 cyclin-dependent kinase inhibitors during hepatocyte differentiation and growth Am J Physiol Gastrointest Liver Physiol 285:G115-G127,2003.
37.Giancarlo Forte,Marilena Minieri,et al;Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells:Proliferation,Migration,and Differentiation;Stem Cells 2006;24;23-33;
38.司煜安,许文荣,严永敏等:体外诱导人骨髓问质干细胞分化为肝细胞样细胞;江苏大学学报(医学版),2008,18(1),6-10
39.Sarah Snykers,Tamara Vanhaecke,et al;Peggy Papeleu,Sequential Exposure to Cytokines Reflecting Embryogenesis:The Key for in vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-like Cells;Toxicological Scinces;2006;94(2),330-341
40.Zoran Ilic,Hyam Leffert,,et al;Sequential Exposure to Cytokines Reflecting Embryogenesis:The Key for In Vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-Like Cells;Toxicological Scinces 94(2),235-239(2006)
41.Theise ND.Gastrointestinal stem cells.III.Emergent themes of liver stem cell biology:niche,quies2 cence,self2renewal,and plasticity[J]Am J Physiol Gastrointest Liver Physiol,2 0 0 6,2 9 0(2 ):G1 8 9-1 9 3.
42.Hynda K Kleinman_,Deborah Philp and Matthew P Hoffman,Role of the extracellular matrix in morphogenesis;Biotechnology:2003,14:526-53
43.Atsushi Suzuki,Atsushi Iwama,Hitoshi Miyashita,et al;Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells;Development anddisease;2003,130,2513-2524
44.周播江,钟翠平,顾云娣等:肝再生大鼠血清诱导骨髓干细胞向肝细胞分化的试验研究;中华肝病杂志;2004,12,730-733
45.李伟,刘苏南,罗端德等;胆汁化血清对骨髓间充质干细胞向肝细胞样细胞定向分化的诱导内科理论与实践:2007年第2卷第4期;260.264
46.Yasuhiro Yamadaa,Eishi Nishirnotoa,Hiroaki Mitsuya;et al;In vitro transdifferentiation of adult bone marrow Sca-1~+ cKit~+ cells cocultured with fetal liver cells into hepatic-like cells without fusion;Experimental Hematology 34(2006) 97-106
47.Meijing Wang,1 Paul R.Crisostomo,1 Christine Herring,et al Human progenitor cells from bone marrow or adipose tissue produce VEGF,HGF,and IGF-I in response to TNF by a p38 MAPK-dependent mechanism;Am J PhysioI Regul Integr Comp Physiol 291:R880-R884,2006.
48.Kazuo Okumoto,Takafumi Saito~*,Etsuko Hattori,et al;Differentiation of rat bone marrow cells cultured on artificial basement membrane containing extracellular matrix into a liver cell lineage Journal of Hepatology 2005,43,110-116
49.Shintaro Yamazaki,Kenji Miki,Tadatoshi Takayama;et al Hepatic gene induction in murine bone marrow after hepatectomy;Journal of Hepatology 44(2006)325-333
50.Kristin M.Braun,Anne W.et el;Hepatic Microenvironment Affects Oval Cell Localization in Albumin-Urokinase-Type Plasminogen Activator Transgenic Mice;Am J Pathol 2003,162:195-202
51. Roberto M. Lemoli, Francesco Bertolini, Ranieri Cancedda, et al; Stem cell plasticity: time for a reappraisal? Haematologica 2005; 90:360-381
52. Yoshitaka Sato, Katsuhide Miyake, et al; Sumoylation of CCAAT/Enhancer-binding Protein _ and Its Functional Roles in Hepatocyte Differentiation;The Journal of Biological Chemistry; 2006.281(31), .21629-21639
53. Xin Wng,Holger Willenbring,et al;Cell fusion is the principal source of bone-marrow-derived hepatocytes; Nature; Apr 24, 2003; 422, 6934; Health & Medical Complete
54. Carla Boccaccio*, Margherita Ando*, and Paolo M. Comoglio;et al; A differentiation switch for genetically modified hepatocytes; The FASEB Journal express article 10.1096/fj.01-0537fje.
55. Laura Erker , Markus ;Grompe; Signaling networks in hepatic oval cell activarionStem Cell Research 2008.10.1016/j.scr.2008.01.002
56. Jason K. Sicklick,Yin-Xiong ,et al;Hedgehog signaling maintains resident hepatic progenitors throughout life; Am J Physiol Gastrointest Liver Physiol 290:G859-G870, 2006
57. Sunny Z. Hussain,a Tamara Sneddon,et al; Wnt impacts growth and differentiation in ex vivo liver development ;Experimental Cell Research 292(2004) 157- 169
58 .Kazuo Okumoto, Takafumi Saito, Etsuko Hattori,et al; Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation;Biochemical and Biophysical Research Communications 304 (2003) 691-695
59. Jixuan Li, Gang Ning, and Stephen A. Duncan; Mammalian hepatocyte differentiation requires the transcription factor HNF-4a;Genes &Development;2000 14:464-474
60. Jean-Bernard Beaudry,l Christophe E.Threshold Levels of Hepatocyte Nuclear Factor 6 (HNF-6) Acting in Synergy with HNF-4 and PGC-1_ Are Required for Time-Specific Gene Expression during Liver Development ; Molecular and cellular biology , Aug. 2006, p. 6037-6046
61. Xavier Prieur, Frank G. Schaap, Herve' Coste;et al; Hepatocyte Nuclear Factor-4_Regulates the Human Apolipoprotein AV Gene: Identification of a Novel Response Element and Involvement in the Control by Peroxisome Proliferator-Activated Receptor-_Coactivator-1_, AMP-Activated Protein Kinase,and Mitogen-Activated Protein Kinase Pathway; Molecular Endocrinology,2005,19(12):3107-3125
62. Celia P. Marti'nez-Jime' nez, Jose' V. Castell, M.et al; Transcriptional Activation of CYP2C9, CYP1A1, and CYP1A2 by Hepatocyte Nuclear Factor 4_ Requires Coactivators Peroxisomal Proliferator Activated Receptor-_ Coactivator 1_and Steroid Receptor Coactivator 1; Mol Pharmacol 70:1681-1692,( 2006)
63. Grahamp.hayhurst,Ying-Hue Lee,et al; Hepatocyte Nuclear Factor 4a (Nuclear Receptor 2Al)Is Essential for Maintenance of Hepatic Gene Expression and Lipid Homeostasis;Molecular and cellular Biologr,Feb.2001.21(4)1393-1403
64. Uzma Samadani and Robert H. Costa; The Transcriptional Activator Hepatocyte Nuclear Factor 6 Regulates Liver Gene Expression; Molecular and cellular biology, Nov. 1996, p. 6273-6284
65. Irene Kynnizi, Pantelis Hatzis, Nitsa Katrakili,et al; Plasticity and expanding complexity of the hepatic transcription factor network during liver development;Genes & Dev. 2006 20: 2293-2305
66. P. Stock, M.S. Staege, L.P. M(?)ller, Hepatocytes Derived From Adult Stem Cells ; Transplantation Proceedings, 2008, 40, 620-623
67. Jai-lin Zhang,Jin Cai,John D,et al;Long-Term Transgene Expression and Survival ofTransgene-Expressing Grafts Following LentivirusTransduction of Bone Marrow Side Population Cells; Transplantation 2005;79: 882-888
68. Anuradha Menthena, Niloyjyoti Deb,et al;Bone Marrow Progenitors Are Not the Source of Expanding Oval Cells in Injured Liver; Stem Cells 2004;22;1049-1061
69. Felix C. Popp, Przemyslaw Slowik,et al;No Contribution of Multipotent Mesenchymal Stromal Cells to Liver Regeneration in a Rat Model of Prolonged Hepatic In(?)ury;Stem Cells 2007;25;639-645;
70.Lorenzo Valfre di Bonzo,Ivana Ferrero,Carlo Cravanzola et al;Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine:Engraftment and hepatocyte differentiation versus profibrogenic potential;Gut,Jul 2007;10.1136/gut.2006.111617.
© 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 |