骨髓基质细胞CD105在异基因造血干细胞移植后植入不良与良好的表达差异
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摘要
目的观察异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,alloHSCT)后植入不良患者与植入良好患者间骨髓基质细胞上黏附分子相关抗原的表达情况。方法收集陆军军医大学(第三军医大学)第二附属医院血液科2016年118例行allo-HSCT患者,根据移植后植入状态将其分为植入良好(good graft function,GGF)组和植入不良(poor graft function,PGF)组,比较两组患者在年龄、原发病、干细胞来源、HLA配型、性别匹配、ABO血型匹配、移植前骨髓增生程度及复发率、病死率等方面的差异;选取其中28例移植后植入不良患者作为研究组,植入良好患者27例作为对照组,提取其行移植术前骨髓活检标本做免疫组织化学染色,抗体选择CD44、CD105、CD29、ICAM-1、VCAM-1,比较上述黏附分子的表达。结果 PGF组与GGF组在年龄、原发病、干细胞来源、HLA配型、性别匹配、ABO血型匹配、移植前骨髓增生程度等因素差异均无统计学意义(P>0.05),而PGF组移植后CMV感染率显著高于GGF组,PGF组移植前缓解率显著低于GGF组,差异均有统计学意义(P<0.05)。经Cox回归分析显示,allo-HSCT后出现PGF的患者生存率明显低于未出现患者(P<0.05,HR=3.598);研究组免疫组化染色CD44、CD29、ICAM-1、VCAM-1表达情况与对照组比较差异无统计学意义(P>0.05),CD105表达水平明显高于对照组(P<0.05)。结论 allo-HSCT后出现植入不良的患者生存率显著下降;移植后植入不良的发生可能与移植前骨髓基质细胞CD105表达升高有关。
Objective To investigate the expression profiles of adhesion molecule-related antigens in bone marrow stromal cells of the recipients with good and poor graft function after allogeneic hematopoietic stem cell transplantation( allo-HSCT). Methods A total of 118 patients underwent allo-HSCT in our department in 2016 were recruited in this study. According to the functional status of the graft after alloHSCT,the recipients were divided into good graft function( GGF) group and poor graft function( PGF) for comparison of age,primary disease,stem cell source,HLA typing,gender matching,ABO blood group matching,bone marrow hyperplasia before transplantation,recurrence rates,and mortality rates. For 28 recipients with PGF and 27 with GGF,the pre-transplant bone marrow biopsy specimens were obtained for immunohistochemical analysis of the adhesion molecules including CD44, CD105, CD29, intercellular adhesion molecule-1( ICAM-1), and vascular cell adhesion molecule-1( VCAM-1). Results The recipients with PGF and GGF did not show significant differences in age,primary disease,stem cell source,HLA typing,gender matching,ABO blood group matching or the degree of bone marrow hyperplasia before transplantation( P > 0. 05). Compared with those with GGF,the recipients with PGF had a significantly higher CMV infection rate after transplantation and a significantly lower remission rate before transplantation( P < 0. 05). Cox regression analysis showed that the recipients with PGF following allo-HSCT had a significantly lower survival rate than those with GGF( P < 0. 05,HR = 3. 598). The expression levels of CD44,CD29,ICAM-1 and VCAM-1 in recipient bone marrow stromal cells were comparable between the recipients with GGF and PGF( P > 0. 05),but the recipients with PGF following allo-HSCT had a significantly higher expression level of CD105 in the stromal cells than those with GGF( P < 0. 05). Conclusion PGF following allo-HSCT is associated with a significantly decreased survival rate of the recipients. The occurrence of PGF following allo-HSCT is probably linked with an increased expression of CD105 in the bone marrow stromal cells of the recipients before transplantation.
Objective To investigate the expression profiles of adhesion molecule-related antigens in bone marrow stromal cells of the recipients with good and poor graft function after allogeneic hematopoietic stem cell transplantation( allo-HSCT). Methods A total of 118 patients underwent allo-HSCT in our department in 2016 were recruited in this study. According to the functional status of the graft after alloHSCT,the recipients were divided into good graft function( GGF) group and poor graft function( PGF) for comparison of age,primary disease,stem cell source,HLA typing,gender matching,ABO blood group matching,bone marrow hyperplasia before transplantation,recurrence rates,and mortality rates. For 28 recipients with PGF and 27 with GGF,the pre-transplant bone marrow biopsy specimens were obtained for immunohistochemical analysis of the adhesion molecules including CD44, CD105, CD29, intercellular adhesion molecule-1( ICAM-1), and vascular cell adhesion molecule-1( VCAM-1). Results The recipients with PGF and GGF did not show significant differences in age,primary disease,stem cell source,HLA typing,gender matching,ABO blood group matching or the degree of bone marrow hyperplasia before transplantation( P > 0. 05). Compared with those with GGF,the recipients with PGF had a significantly higher CMV infection rate after transplantation and a significantly lower remission rate before transplantation( P < 0. 05). Cox regression analysis showed that the recipients with PGF following allo-HSCT had a significantly lower survival rate than those with GGF( P < 0. 05,HR = 3. 598). The expression levels of CD44,CD29,ICAM-1 and VCAM-1 in recipient bone marrow stromal cells were comparable between the recipients with GGF and PGF( P > 0. 05),but the recipients with PGF following allo-HSCT had a significantly higher expression level of CD105 in the stromal cells than those with GGF( P < 0. 05). Conclusion PGF following allo-HSCT is associated with a significantly decreased survival rate of the recipients. The occurrence of PGF following allo-HSCT is probably linked with an increased expression of CD105 in the bone marrow stromal cells of the recipients before transplantation.
引文
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[15]王晓宁,张梅,贺鹏程,等.异基因造血干细胞移植中回输造血干细胞的量和回输时受者白细胞数与疾病预后关系分析[J].中国实验血液学杂志,2013,21(6):1530-1534.DOI:10.7534/j.issn.1009-2137.2013.06.031.WANG X N,ZHANG M,HE P C,et al.Relation of reinfused hematopoietic stem cell volume and recipient's leukocyte count at reinfusion with prognosis of disease in allohematopoietic stem cell transplantation[J].J Exp Hematol,2013,21(6):1530-1534.DOI:10.7534/j.issn.1009-2137.2013.06.031.
[16]蔡雪娇,孙岚,谢作听,等.ABO血型不合对清髓异基因造血干细胞移植造血重建的影响[J].中华移植杂志:电子版,2012,6(4):250-253.DOI:10.3877/cma.j.issn.1647-3903.2012.04.004.CAI X J,SUN L,XIE Z T,et al.Effect of ABOincompatible myeloablative allogeneic hematopoietic stem cell transplantation on hematopoietic engraftment[J].Chin J Transplant(Electronic Edition),2012,6(4):250-253.DOI:10.3877/cma.j.issn.1647-3903.2012.04.004.
[17]宋国梁,潘彬,齐昆明,等.HSCT联合不同剂量内皮祖细胞输注对小鼠造血重建的影响[J].中华器官移植杂志,2011,32(11):688-692.DOI:10.3760/cma.j.issn.0254-1785.2011.11.012.SONG G L,PAN B,QI K M,et al.Effects of endothelial progenitor cell combined with allogeneic bone marrow transplantation on hematopoietic reconstitution in mice[J].Chin J Organ Transplant,2011,32(11):688-692.DOI:10.3760/cma.j.issn.0254-1785.2011.11.012.
[18]杨贞,吴德沛,徐杨,等.造血干细胞移植前营养状态与造血重建的关系[J].中华血液学杂志,2012,33(6):496-498.DOI:10.3760/cma.j.issn.0253-2727.2012.06.019.YANG Z,WU D P,XU Y,et al.Relationship between nutritional status and hematopoietic reconstitution before transplantation of hematopoietic stem cells[J].Chin J Hematol,2012,33(6):496-498.DOI:10.3760/cma.j.issn.0253-2727.2012.06.019.
[2]马俐君,胡晓霞,周虹,等.间充质干细胞与人脐血CD34+细胞共移植对NOD/SCID小鼠造血重建的影响[J].中华血液学杂志,2008,29(10):684-688.DOI:10.3321/j.issn:0253-2727.2008.10.009.MA L J,HU X X,ZHOU H,et al.Study on hematopoiesis reconstitution by co-transplant of human bone marrow mesenchymal stem cells and umbilical cord blood CD34+cells at different ratios in NOD/SCID mice[J].Chin J Hematol,2008,29(10):684-688.DOI:10.3321/j.issn:0253-2727.2008.10.009.
[3]HAEN S P,SCHUMM M,FAUL C,et al.Poor graft function can be durably and safely improved by CD34+-selected stem cell boosts after allogeneic unrelated matched or mismatched hematopoietic cell transplantation[J].J Cancer Res Clin Oncol,2015,141(12):2241-2251.DOI:10.1007/s00432-015-2027-x.
[4]MASOURIDI-LEVRAT S,SIMONETTA F,CHALANDON Y.Immunological basis of bone marrow failure after allogeneic hematopoietic stem cell transplantation[J].Front Immunol,2016,7(4):362.DOI:10.3389/fimmu.2016.00362.
[5]KONG Y,WANG Y T,HU Y,et al.The bone marrow micro environment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function[J].Bone Marrow Transplant,2016,51(2):249-255.DOI:10.1038/bmt.2015.229.
[6]SNELL M,CHAU C,HENDRIX D,et al.Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation[J].Bone Marrow Transplant,2006,38(2):135-140.DOI:10.1038/sj.bmt.1705409.
[7]KONG Y,CHANG Y J,WANG Y Z,et al.Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation[J].Biol Blood Marrow Transplant,2013,19(10):1465-1473.DOI:10.1016/j.bbmt.2013.07.014.
[8]STASIA A,GHISO A,GALAVERNA F,et al.CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation[J].Biol Blood Marrow Transplant,2014,20(9):1440-1443.DOI:10.1016/j.bbmt.2014.05.016.
[9]李明辉,田丁,刘聪燕,等.人骨髓间充质干细胞的培养及研究[J].首都医科大学学报,2005,26(2):183-186.LI M H,TIAN D,LIU C Y,et al.Culture of human bone marrow mesenchymal stem cells[J].J Capital Med Univ,2005,26(2):183-186.
[10]李梅,朱艳华,张瑜,等.CD105的研究现状[J].现代医药卫生,2004,20(21):2255-2256.LI M,ZHU Y H,ZHANG Y,et al.Research status of CD105[J].Mod Med Health,2004,20(21):2255-2256.
[11]常城,陈幸华,孔佩艳,等.全反式维甲酸对外周血干细胞移植患者骨髓基质细胞黏附分子表达及黏附力的影响[J].中国实验血液学杂志,2006,14(4):768-772.CHANG C,CHEN X H,KONG P Y,et al.In vitro effect of all-trans retinoic acid on cell adhesion molecule expression and adhesion capacity of bone marrow stromal cells in patients received peripheral blood stem cell transplantation[J].J Exp Hematol,2006,14(4):768-772.
[12]FONSATTI E,DEL VECCHIO L,ALTOMONTE M,et al.Endoglin:an accessory component of the TGF-beta-binding receptor-complex with diagnostic,prognostic,and bioimmunotherapeutic potential in human malignancies[J].J Cell Physiol,2001,188(1):1-7.DOI:10.1002/jcp.1095.
[13]WANG J M,KUMAR S,PYE D,et al.Breast carcinoma:comparative study of tumor vasculature using two endothelial cell markers[J].J Natl Cancer Inst,1994,86(5):386-388.DOI:10.1093/jnci/86.5.386.
[14]AKAGI K,IKEDA Y,SUMIYOSHI Y,et al.Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development[J].Surgery,2002,131(1suppl):S109-S113.DOI:10.1067/msy.2002.119361.
[15]王晓宁,张梅,贺鹏程,等.异基因造血干细胞移植中回输造血干细胞的量和回输时受者白细胞数与疾病预后关系分析[J].中国实验血液学杂志,2013,21(6):1530-1534.DOI:10.7534/j.issn.1009-2137.2013.06.031.WANG X N,ZHANG M,HE P C,et al.Relation of reinfused hematopoietic stem cell volume and recipient's leukocyte count at reinfusion with prognosis of disease in allohematopoietic stem cell transplantation[J].J Exp Hematol,2013,21(6):1530-1534.DOI:10.7534/j.issn.1009-2137.2013.06.031.
[16]蔡雪娇,孙岚,谢作听,等.ABO血型不合对清髓异基因造血干细胞移植造血重建的影响[J].中华移植杂志:电子版,2012,6(4):250-253.DOI:10.3877/cma.j.issn.1647-3903.2012.04.004.CAI X J,SUN L,XIE Z T,et al.Effect of ABOincompatible myeloablative allogeneic hematopoietic stem cell transplantation on hematopoietic engraftment[J].Chin J Transplant(Electronic Edition),2012,6(4):250-253.DOI:10.3877/cma.j.issn.1647-3903.2012.04.004.
[17]宋国梁,潘彬,齐昆明,等.HSCT联合不同剂量内皮祖细胞输注对小鼠造血重建的影响[J].中华器官移植杂志,2011,32(11):688-692.DOI:10.3760/cma.j.issn.0254-1785.2011.11.012.SONG G L,PAN B,QI K M,et al.Effects of endothelial progenitor cell combined with allogeneic bone marrow transplantation on hematopoietic reconstitution in mice[J].Chin J Organ Transplant,2011,32(11):688-692.DOI:10.3760/cma.j.issn.0254-1785.2011.11.012.
[18]杨贞,吴德沛,徐杨,等.造血干细胞移植前营养状态与造血重建的关系[J].中华血液学杂志,2012,33(6):496-498.DOI:10.3760/cma.j.issn.0253-2727.2012.06.019.YANG Z,WU D P,XU Y,et al.Relationship between nutritional status and hematopoietic reconstitution before transplantation of hematopoietic stem cells[J].Chin J Hematol,2012,33(6):496-498.DOI:10.3760/cma.j.issn.0253-2727.2012.06.019.