中国组织工程研究与临床康复
中國組織工程研究與臨床康複
중국조직공정연구여림상강복
JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH
2009年
53期
10457-10460
,共4页
王志余%葛永超%赵晓武%吴书一%常保东
王誌餘%葛永超%趙曉武%吳書一%常保東
왕지여%갈영초%조효무%오서일%상보동
肾移植%骨髓细胞%急性排斥%嵌合体
腎移植%骨髓細胞%急性排斥%嵌閤體
신이식%골수세포%급성배척%감합체
背景:特异性的供者骨髓造血干细胞输注促进了嵌合体的形成,可以诱导器官移植免疫耐受.然而为达到细胞嵌合进行骨髓移植的预处理毒性大,发生移植物抗宿主反应的风险较高,人们开始寻找一些毒性更小的方案,其中包括免疫抑制剂联合骨髓输注等,尽管动物实验中已有诱导成功的耐受模型,但临床实用的诱导耐受方法则难以突破.目的:以嵌合体理论为基础,分析肾-骨髓联合移植诱导嵌合体形成与免疫耐受的相关性及安全性. 设计、时间及地点:对比观察,于1998-01/2005-12在郑州市第三人民医院泌尿外科完成.对象:根据ABO/Rh血型相同及HLA配型原则,将同期等待肾移植的96例女性慢性肾功能衰竭患者分为2组,每组48例.联合移植组患者接受尸体肾、骨髓联合移植;同期接受上述同一供者另一肾脏的尿毒症患者作为对照组.供者为48例健康男性.方法:供者在取肾的同时,采集骨髓加入细胞冷冻保养液,经细胞程序降温至-198 ℃液氮罐保存.移植后应用大剂量抗人T淋巴细胞免疫球蛋白诱导治疗2周,于肾脏移植后2周实施骨髓细胞回输,输注的单个核细胞数为(0.9～2.5)×10~8/kg.采用聚合酶链反应方法检测人性别决定基因SRY.抽血检测CD3,CD4,CD8,CD25,以酶联免疫吸附法测定血白细胞介素10、肿瘤坏死因子α、肿瘤坏死因子β等血细胞因子质量浓度.主要观察指标:移植后于不同时间点对受体进行嵌合体、淋巴细胞亚群及细胞因子检测.随访观察两组受者的临床移植效果及并发症发生情况.结果:联合移植组嵌合体阳性率显著高于对照组(P < 0.05).随访3年,嵌合体阳性受者和嵌合体阴性受者排斥发生率差异具有显著性意义(13%,35%,P < 0.05).联合移植组呈现免疫抑制状态,未见移植物抗宿主病发生.结论:肾-骨髓联合移植能促进移植后嵌合体的形成,显著降低排斥反应发生率,是一种安全有效的诱导免疫耐受的方法.
揹景:特異性的供者骨髓造血榦細胞輸註促進瞭嵌閤體的形成,可以誘導器官移植免疫耐受.然而為達到細胞嵌閤進行骨髓移植的預處理毒性大,髮生移植物抗宿主反應的風險較高,人們開始尋找一些毒性更小的方案,其中包括免疫抑製劑聯閤骨髓輸註等,儘管動物實驗中已有誘導成功的耐受模型,但臨床實用的誘導耐受方法則難以突破.目的:以嵌閤體理論為基礎,分析腎-骨髓聯閤移植誘導嵌閤體形成與免疫耐受的相關性及安全性. 設計、時間及地點:對比觀察,于1998-01/2005-12在鄭州市第三人民醫院泌尿外科完成.對象:根據ABO/Rh血型相同及HLA配型原則,將同期等待腎移植的96例女性慢性腎功能衰竭患者分為2組,每組48例.聯閤移植組患者接受尸體腎、骨髓聯閤移植;同期接受上述同一供者另一腎髒的尿毒癥患者作為對照組.供者為48例健康男性.方法:供者在取腎的同時,採集骨髓加入細胞冷凍保養液,經細胞程序降溫至-198 ℃液氮罐保存.移植後應用大劑量抗人T淋巴細胞免疫毬蛋白誘導治療2週,于腎髒移植後2週實施骨髓細胞迴輸,輸註的單箇覈細胞數為(0.9～2.5)×10~8/kg.採用聚閤酶鏈反應方法檢測人性彆決定基因SRY.抽血檢測CD3,CD4,CD8,CD25,以酶聯免疫吸附法測定血白細胞介素10、腫瘤壞死因子α、腫瘤壞死因子β等血細胞因子質量濃度.主要觀察指標:移植後于不同時間點對受體進行嵌閤體、淋巴細胞亞群及細胞因子檢測.隨訪觀察兩組受者的臨床移植效果及併髮癥髮生情況.結果:聯閤移植組嵌閤體暘性率顯著高于對照組(P < 0.05).隨訪3年,嵌閤體暘性受者和嵌閤體陰性受者排斥髮生率差異具有顯著性意義(13%,35%,P < 0.05).聯閤移植組呈現免疫抑製狀態,未見移植物抗宿主病髮生.結論:腎-骨髓聯閤移植能促進移植後嵌閤體的形成,顯著降低排斥反應髮生率,是一種安全有效的誘導免疫耐受的方法.
배경:특이성적공자골수조혈간세포수주촉진료감합체적형성,가이유도기관이식면역내수.연이위체도세포감합진행골수이식적예처리독성대,발생이식물항숙주반응적풍험교고,인문개시심조일사독성경소적방안,기중포괄면역억제제연합골수수주등,진관동물실험중이유유도성공적내수모형,단림상실용적유도내수방법칙난이돌파.목적:이감합체이론위기출,분석신-골수연합이식유도감합체형성여면역내수적상관성급안전성. 설계、시간급지점:대비관찰,우1998-01/2005-12재정주시제삼인민의원비뇨외과완성.대상:근거ABO/Rh혈형상동급HLA배형원칙,장동기등대신이식적96례녀성만성신공능쇠갈환자분위2조,매조48례.연합이식조환자접수시체신、골수연합이식;동기접수상술동일공자령일신장적뇨독증환자작위대조조.공자위48례건강남성.방법:공자재취신적동시,채집골수가입세포냉동보양액,경세포정서강온지-198 ℃액담관보존.이식후응용대제량항인T림파세포면역구단백유도치료2주,우신장이식후2주실시골수세포회수,수주적단개핵세포수위(0.9～2.5)×10~8/kg.채용취합매련반응방법검측인성별결정기인SRY.추혈검측CD3,CD4,CD8,CD25,이매련면역흡부법측정혈백세포개소10、종류배사인자α、종류배사인자β등혈세포인자질량농도.주요관찰지표:이식후우불동시간점대수체진행감합체、림파세포아군급세포인자검측.수방관찰량조수자적림상이식효과급병발증발생정황.결과:연합이식조감합체양성솔현저고우대조조(P < 0.05).수방3년,감합체양성수자화감합체음성수자배척발생솔차이구유현저성의의(13%,35%,P < 0.05).연합이식조정현면역억제상태,미견이식물항숙주병발생.결론:신-골수연합이식능촉진이식후감합체적형성,현저강저배척반응발생솔,시일충안전유효적유도면역내수적방법.
BACKGROUND: Infusion of hemopoietic stem cell from donors can promote the chimeric formation and induce specific immunologic tolerance in the allograft recipients. However, the pretreatment for cell transplantation has great toxicity to recipients. So immunosuppressant combined bone marrow infusion is introduced to anti graft versus host reaction. OBJECTIVE: Based on microchimerism, to study the security and associativity of chimera formation induced by kidney-bone marrow transplantation and immunologic tolerance.DESIGN, TIME AND SETTING: The contrast observation was performed at the department of urinary surgery, The Third People's Hospital of Zhengzhou City from January 1998 to December 2005.PARTICIPANTS: According to ABO/Rh blood type and HLA matching, 96 female patients with chronic renal failure and waiting for kidney transplantation were divided into 2 groups, In the combination group, patients received kidney combined bone marrow transplantation; the other uremia patients received the other kidney of cadavers were served as control group. The donors were 48 healthy males. METHODS: Bone marrow of donors was collected simultaneously with kidney obtain and preserved with cryoprotectant at -198 ℃ in nitrogen canister. After kidney transplantation, large dose of anti-human lymphocyte immune globulin were used for 2 weeks, then (0.9-2.5)×10~8/kg mononuclearcell was reinfused. PCR-SRY was used to identify donor derived cell-chimerism. Lymphocyte subgroup of recipients was determined by blood test; and interleukin 10 was measured by enzyme linked immunosorbent assay; in addition, the mass concentration of tumor necrosis factor α and tumor necrosis factor β was detected. MAIN OUTCOME MEASURES: Chimerism, lymphocyte subsets and cytokines were detected at various time points following transplantation. Simultaneously, the transplantation results and complication status of recipients were observed. RESULTS: The positive rate of chimera in the combination group was greater than that of the control group (P < 0.05). The 3-year follow-up showed that incidence differences of acute rejection between recipients with positive chimera and recipients with negative chimera had significance (13%, 35%, P < 0.05). There was no graft versus host disease occurred in the combination group. CONCLUSION: Kidney-bone marrow transplantation can augment chimerism in early postoperative period, and significantly reduce the rate of acute rejection, which is safe and beneficia1to induce specific immunologic tolerance in the renal allograft recipients.
