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

doi:10.3969/j.issn.2095-4344.1717

Abstract

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

CLC Number:

R457

Wang Xiaoning, Chen Ying, Zhu Huachao, Zhang Mei, He Pengcheng. Protective effect of human umbilical cord mesenchymal stem cells on acute drug-induced liver injury after conditioning in haploidentical hematopoietic stem cell transplantation[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(17): 2690-2695.

Figures/Tables 4

2.4 移植后移植物抗宿主病、肝静脉闭塞病及病毒感染观察组5例患者在移植后28-100 d内发生急性移植物抗宿主病(Ⅱ度2例，Ⅲ度3例)，对照组14例患者在移植后18-100 d内发生急性移植物抗宿主病(Ⅱ度9例，Ⅲ度4例，Ⅳ度1例)。所有患者中无一例发生肝静脉闭塞病。对照组中1例既往乙肝及1例既往丙肝感染患者治疗后均没有出现病毒再激活，监测HCV-DNA及HCV-RNA定量均为阴性。两组患者预处理后4周内观察组有1例出现CMV-DNA定量升高，对照组有9例出现CMV-DNA定量升高，无一例发生CMV病及EB-DNA定量升高。 2.5 两组患者肝功生化指标比较两组患者预处理前肝功均正常，预处理后第1天、第1，2，4周肝功生化指标变化如下：与预处理前比较，预处理结束第1天，对照组血清谷丙转氨酶、碱性磷酸酶、谷氨酰胺转移酶及直接胆红素增高，观察组谷丙转氨酶、谷氨酰胺转移酶增高；观察组谷丙转氨酶、谷草转氨酶、谷氨酰胺转移酶、碱性磷酸酶及直接胆红素值较对照组显著降低，差异有显著性意义(P < 0.05)，见表2。预处理后第2周，观察组肝功各项指标与预处理后第1天比较逐渐下降，对照组谷丙转氨酶、碱性磷酸酶及直接胆红素均增高，观察组谷丙转氨酶、谷草转氨酶、谷氨酰胺转移酶、碱性磷酸酶值较对照组显著降低，差异有显著性意义(P < 0.05)，见表3。预处理后第4周，两组患者谷丙转氨酶、谷草转氨酶正常，谷氨酰胺转移酶、碱性磷酸酶、直接胆红素轻度升高，两组间差异无显著性意义(P > 0.05)，见表4。两组患者谷丙转氨酶、谷草转氨酶、碱性磷酸酶、谷氨酰胺转移酶变化，见图2和图3。 2.6 药物性肝损害类型及严重程度比较预处理后1个月内所有患者均未发生急性移植物抗宿主病及肝静脉闭塞病，观察组患者3例肝功正常，5例发生急性药物性肝损害，对照组2例患者肝功正常，15例发生急性药物性肝损害，两组患者肝损害类型及严重程度见表5，均以肝细胞损伤型及轻度肝损害为主。"

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