中国组织工程研究 ›› 2014, Vol. 18 ›› Issue (32): 5140-5145.doi: 10.3969/j.issn.2095-4344.2014.32.010

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

自身骨髓间充质干细胞治疗慢性移植物肾病的安全性与可行性

张  磊1,陈  正1,谢斯盛1,2,马俊杰1,方佳丽1,李光辉1,徐  璐1,张异蕊1,郭予和1,潘光辉1   

  1. 1广州医科大学附属第二医院器官移植科,广东省广州市  510260;2东莞市人民医院泌尿外科,广东省东莞市  523000
  • 收稿日期:2014-06-28 出版日期:2014-08-06 发布日期:2014-09-18
  • 通讯作者: 潘光辉,主任医师,广州医科大学附属第二医院器官移植科,广东省广州市 510260
  • 作者简介:张磊,男,1982年生,河南省信阳市人,汉族,2010年中山大学毕业,博士,主治医师,主要从事肾移植及相关免疫领域研究。
  • 基金资助:

    广东省科技计划项目《肾移植受体自身MSCs诱导免疫耐受及治疗慢性移植肾肾病的临床研究》,项目编号:2010B031600296;广州医科大学博士启动基金项目《BM-MSC对肾脏缺血再灌注损伤所致晚期炎症介质HMGB1的调控及其机制研究》,项目编号:2010C29

Safety and feasibility of autologous bone marrow mesenchymal stem cells in treating chronic allograft nephropathy

Zhang Lei1, Chen Zheng1, Xie Si-sheng1, 2, Ma Jun-jie1, Fang Jia-li1, Li Guang-hui1, Xu Lu1, Zhang Yi-rui1, Guo Yu-he1, Pan Guang-hui1   

  1. 1Department of Organ Transplantation, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China; 2Department of Urology, Dongguan People’s Hospital, Dongguan 523000, Guangdong Province, China
  • Received:2014-06-28 Online:2014-08-06 Published:2014-09-18
  • Contact: Pan Guang-hui, Chief physician, Department of Organ Transplantation, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
  • About author:Zhang Lei, M.D., Attending physician, Department of Organ Transplantation, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
  • Supported by:

    the Science and Technology Plan of Guangdong Province, No. 2010B031600296; the Doctoral Startup Fund of Guangzhou Medical University, No. 2010C29

摘要:

背景:慢性移植物肾病是肾移植领域较难处理的一种临床并发症,大多数最终会发展为移植肾失功。骨髓间充质干细胞作为一种低免疫原性的特殊细胞群,已证实具有分化、转分化、旁分泌等多种功能,在临床其他领域已有成功应用的基础。基于此特点,将其应用于慢性移植物肾病的患者可能会起到一定的治疗作用。
目的:探讨数字减影动脉造影引导下经移植肾动脉输注及之后经静脉输注自身骨髓间充质干细胞治疗慢性移植物肾病的安全性与可行性。
方法:选择2011年3月至2013年1月间确诊慢性移植物肾病且符合入组标准的患者11例,行1次数字减影动脉造影引导下经移植肾动脉输注及之后2次经静脉输注骨髓间充质干细胞。观察治疗后1年内患者血肌酐、尿素氮、内生肌酐清除率、胱抑素C、24 h尿蛋白、血/尿β2微球蛋白的变化情况。
结果与结论:11例患者未发生出血、移植肾动脉栓塞、假性动脉瘤等相关并发症。骨髓间充质干细胞治疗后1周、1个月时血肌酐、尿素氮、胱抑素C水平与治疗前相比明显下降,其差异有显著性意义(P < 0.05);治疗3个月后,各指标与治疗前比较差异无显著性意义(P > 0.05)。骨髓间充质干细胞治疗后1周、1个月时内生肌酐清除率较治疗前升高,其差异有显著性意义(P < 0.05);而治疗3个月后与治疗前比较差异无显著性意义(P > 0.05)。治疗7 d时24 h尿蛋白水平与治疗前相比明显下降,其差异有显著性意义(P < 0.05),而治疗1个月后差异无显著性意义(P > 0.05);血/尿β2微球蛋白治疗前后均无明显变化。结果可见数字减影动脉造影引导下经移植肾动脉输注及经静脉输注骨髓间充质干细胞治疗慢性移植物肾病是安全的,对患者肾功能改善有一定效果,输注细胞剂量及后续输注方式的选择尚有待研究。


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程


全文链接:

关键词: 干细胞, 移植, 慢性移植物肾病, 骨髓间充质干细胞, 肾功能, 安全性

Abstract:

BACKGROUND: Chronic allograft nephropathy is a complication of kidney transplantation and most of patients will eventually develop transplant kidney dysfunction. Bone marrow mesenchymal stem cells as a low immunogenicity special cell population have been shown to have differentiation, transdifferentiation, paracrine and other basic functions, which have been successful used in other clinical areas. Based on this characteristic, bone marrow mesenchymal stem cells may play a therapeutic role in chronic allograft nephropathy.
OBJECTIVE: To study the safety and feasibility of autologus bone marrow mesenchymal stem cells transplantation via renal artery infusion and subsequent intravenous infusion guided by the digital subtraction angiography in the treatment of chronic allograft nephropathy. 
METHODS: Eleven patients with chronic allograft nephropathy who were confirmed from March 2011 to January 2013 were enrolled, and then received transplant renal artery infusion once guided by the digital subtraction angiography and subsequent intravenous infusion twice of bone marrow mesechymal stem cells. Changes in serum creatinine, blood urea nitrogen, creatinine clearance, cystatin C, 24-hour urine protein, and β2 microglobulin in the blood and urinary were monitored in patients up to 1 year after treatment.
RESULTS AND CONCLUSION: Bleeding, transplant renal artery embolization, pseudoaneurysm and other related complications were not found in any of the 11 patients. The levels of serum creatinine, blood urea nitrogen and cystatin C were significantly decreased at 1 week and 1 month after cell therapy (P < 0.05), while after 3 months of treatment, there was no difference before and after treatment (P > 0.05). The creatinine clearance at 1 week and 1 month after treatment showed a remarkable increase, which were significantly different from that before treatment (P < 0.05), but after 3 months of treatment, the difference was not significant (P > 0.05). The level of 24-hour urine protein was significantly decreased after 7 days of treatment (P < 0.05), and no difference was found after 1 month (P > 0.05). The level of β2 microglobulin in the blood and urinary had no changes before and after treatment. These findings indicate that guided by the digital subtraction angiography, bone marrow mesenchymal stem cells via the renal artery infusion and subsequent intravenous infusion can improve kidney function of patients, but the cell dosage and infusion method remain to be solved.


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程


全文链接:

Key words: bone marrow, mesenchymal stem cells, kidney transplantation, postoperative complications, nephrosis, kidney function tests

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