中国组织工程研究

中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (17): 2690-2695.doi: 10.3969/j.issn.2095-4344.1717

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

脐血间充质干细胞对半相合造血干细胞移植预处理后急性药物性肝损害的保护作用

王晓宁，陈 颖，朱化超，张 梅，贺鹏程   

  1. 西安交通大学第一附属医院血液内科，陕西省西安市 710061
  • 修回日期:2019-01-26 出版日期:2019-06-18 发布日期:2019-06-18
  • 通讯作者: 张梅，教授，西安交通大学第一附属医院血液内科，陕西省西安市 710061； 并列通讯作者：贺鹏程，教授，西安交通大学第一附属医院血液内科，陕西省西安市 710061
  • 作者简介:王晓宁，女，1982年生，陕西省榆林市人，汉族，2015年西安交通大学毕业，博士，副主任医师，主要从事造血干细胞的基础及临床研究。
  • 基金资助:

    国家自然科学基金青年项目(81600179)，项目负责人：王晓宁

Protective effect of human umbilical cord mesenchymal stem cells on acute drug-induced liver injury after conditioning in haploidentical hematopoietic stem cell transplantation

Wang Xiaoning, Chen Ying, Zhu Huachao, Zhang Mei, He Pengcheng   

  1. Department of Hematology, the First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
  • Revised:2019-01-26 Online:2019-06-18 Published:2019-06-18
  • Contact: Zhang Mei, Professor, Department of Hematology, the First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China; He Pengcheng, Professor, Department of Hematology, the First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
  • About author:Wang Xiaoning, MD, Associate chief physician, Department of Hematology, the First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, China
  • Supported by:

    the National Natural Science Foundation of China (Youth Program), No. 81600179 (to WXN)

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摘要：

文章快速阅读：

文题释义：
预处理后急性药物性肝损害：造血干细胞移植中受者需要接受大剂量化疗或放疗清除体内残留的肿瘤细胞，称为预处理。化疗预处理剂量为常规化疗剂量的数倍，甚至为致死剂量，因此极易引起急性药物性肝损害。
制约半相合造血干细胞移植广泛开展的主要原因：由于其供者来源广泛，逐渐成为目前国内造血干细胞移植的主流模式，制约其广泛开展的主要原因是移植物抗宿主病及植入失败发生率高于全相合造血干细胞移植。为了解决这两大难题，目前部分移植中心采用联合间充质干细胞共移植的方法促进造血干细胞植入，降低了移植物抗宿主病的发生率。

 

摘要
背景：半相合造血干细胞移植是目前国内移植的主流模式，制约其广泛开展的主要原因是移植物抗宿主病及植入失败发生率高于全相合造血干细胞移植。为了解决这两大难题，目前部分移植中心采用联合间充质干细胞共移植的方法促进造血干细胞植入，同时降低移植物抗宿主病的发生率。已有研究显示间充质干细胞对肝硬化及肝炎患者损伤肝细胞有促进修复的作用。共移植间充质干细胞能否预防急性药物性肝损害尚不明确。
目的：观察半相合造血干细胞移植时输注脐血间充质干细胞对急性药物性肝损害的预防保护作用。
方法：回顾性分析2010年1月至2017年8月期间行半相合造血干细胞移植患者的临床资料，其中观察组8例在回输造血干细胞前4-6 h内输注脐血间充质干细胞1×106/kg，对照组17例未联合输注脐血间充质干细胞，观察两组患者在预处理后1 d、2周及4周的肝功能指标变化以及治疗转归。经西安交通大学医学院第一附属医院伦理委员会评审，此试验方案及知情同意书可行，符合伦理原则(批件号：2016伦审临字第(20)号)。
结果与结论：①两组患者预处理后均有不同程度的肝脏生化学指标异常，2周达高峰，4周后趋于正常；②在预处理后1 d及2周时，观察组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、谷氨酰胺转移酶、直接胆红素值较对照组降低，差异有显著性意义(P < 0.05)；③两组患者输注造血干细胞及脐血间充质干细胞期间无发热、血压升高/降低、心律失常及溶血等不良反应；④结果表明，半相合造血干细胞移植中共回输脐血间充质干细胞能降低预处理后急性药物性肝损害的程度，对肝脏起到一定的保护作用，需要进一步扩大病例数进行临床观察。


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
ORCID: 0000-0002-2472-4076(王晓宁)

关键词: 半相合造血干细胞移植, 脐血间充质干细胞, 药物性肝损害, 肝功能, 移植预处理, 移植物抗宿主病, 国家自然科学基金

Abstract:

BACKGROUND: Haploidentical hematopoietic stem cell transplantation is currently the mainstream mode of transplantation in China, but its widespread development is restricted by the higher incidence of graft-versus-host disease and implantation failure as compared with HLA identical hematopoietic stem cell transplantation. In order to solve these two problems, co-transplantation of mesenchymal stem cells and hematopoietic stem cells is used in some transplant centers to promote hematopoietic stem cell transplantation, and to reduce the incidence of graft-versus-host disease. Studies have shown that mesenchymal stem cells can promote the repair of liver cells in liver cirrhosis and hepatitis patients. It is unclear whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells can prevent acute drug-induced liver injury.
OBJECTIVE: To investigate the preventive and protective effects of infusion of umbilical cord blood mesenchymal stem cells on acute drug-induced liver injury after conditioning in haploidentical hematopoietic stem cell transplantation. 
METHODS: Clinical data of patients who underwent haploidentical hematopoietic stem cell transplantation from January 2010 to August 2017 was retrospectively analyzed. Eight cases were transfused with umbilical cord blood mesenchymal stem cells 1×106/kg within 4-6 hours before transfusion of hematopoietic stem cells. Seventeen-seven cases in the control group were not given umbilical cord blood mesenchymal stem cells. The changes of liver function indicators and treatment outcomes at 1 day, 2 weeks and 4 weeks after transplantation conditioning were observed. The study protocol was approved by the ethics committee of the First Affiliated Hospital of Xi’an Jiao Tong University with the approval No. 2016(20). Written informed consent was obtained prior to the initiation of the study. 
RESULTS AND CONCLUSION: (1) Patients in both groups had abnormalities in the biomedical indicators of liver function to different extent. These indicators peaked at 2 weeks post preconditioning, and then became normal after 4 weeks. (2) The levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, transglutaminase, and direct bilirubin were significantly lower in the observation group than the control group at 1 day and 2 weeks after transplantation conditioning (P < 0.05). (3) There were no adverse reactions such as fever, blood pressure increase/decrease, arrhythmia and hemolysis in the two groups during the infusion of hematopoietic stem cells and umbilical cord blood mesenchymal stem cells. These findings reveal that co-transfusion of umbilical cord blood mesenchymal stem cells during haploidentical hematopoietic stem cell transplantation may reduce acute drug-induced liver injury after transplantation conditioning, and it needs to be further investigated duo to limit numbers of patients.

Key words: haploidentical hematopoietic stem cell transplantation, umbilical cord blood mesenchymal stem cells, drug-induced liver damage, liver function, transplantation conditioning, graft-versus-host disease, National Natural Science Foundation of China

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