Recombinant human thrombopoietin reduces the risk of acute graft-versus-host-disease and its mechanism

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology Pub Date : 2025-05-31 DOI:10.1016/j.trim.2025.102246

Hairong Fei , Xiaodan Liu , Xiaolin Ma , Feng Hou , Peng Jiang , Lingjie Sun , Shanshan Liu , Tianlan Li , Chunting Zhao

{"title":"Recombinant human thrombopoietin reduces the risk of acute graft-versus-host-disease and its mechanism","authors":"Hairong Fei , Xiaodan Liu , Xiaolin Ma , Feng Hou , Peng Jiang , Lingjie Sun , Shanshan Liu , Tianlan Li , Chunting Zhao","doi":"10.1016/j.trim.2025.102246","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of recombinant human thrombopoietin (rhTPO) on aGVHD using retrospective clinical data and a xenogeneic GVHD mouse model.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 162 patients who underwent allo-HSCT between 2016 and 2018, comparing outcomes between those treated with rhTPO and those who were not. Additionally, a murine GVHD model was established using irradiated Balb/c mice that received allogeneic PBMCs. Mice were treated with different doses of rhTPO to assess organ pathology, immune cell subsets, and cytokine expression. PBMCs from humans were also treated with rhTPO to assess proliferation and differentiation in vitro. Results were presented as odds ratios (OR) with 95 % confidence intervals (CI), and statistical significance was set at <em>P</em> < 0.05. <em>P</em> > 0.05 was considered statistically significant. All experiments were repeated for 3 times.</div></div><div><h3>Results</h3><div>Clinical analysis showed that rhTPO use and older patient age were independently associated with a lower incidence of aGVHD (<em>P</em> = 0.007 and <em>P</em> = 0.014, respectively). In the xenogeneic mouse model, rhTPO mitigated tissue pathology and modulated immune cell subsets. In vitro, rhTPO regulated PBMC proliferation and enhanced lymphocyte differentiation.</div></div><div><h3>Conclusions</h3><div>rhTPO may reduce the risk of aGVHD by modulating immune responses and protecting tissues, supporting its potential role as an adjunct therapy in allo-HSCT.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102246"},"PeriodicalIF":1.4000,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplant immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0966327425000747","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of recombinant human thrombopoietin (rhTPO) on aGVHD using retrospective clinical data and a xenogeneic GVHD mouse model.

Methods

We retrospectively analyzed 162 patients who underwent allo-HSCT between 2016 and 2018, comparing outcomes between those treated with rhTPO and those who were not. Additionally, a murine GVHD model was established using irradiated Balb/c mice that received allogeneic PBMCs. Mice were treated with different doses of rhTPO to assess organ pathology, immune cell subsets, and cytokine expression. PBMCs from humans were also treated with rhTPO to assess proliferation and differentiation in vitro. Results were presented as odds ratios (OR) with 95 % confidence intervals (CI), and statistical significance was set at P < 0.05. P > 0.05 was considered statistically significant. All experiments were repeated for 3 times.

Results

Clinical analysis showed that rhTPO use and older patient age were independently associated with a lower incidence of aGVHD (P = 0.007 and P = 0.014, respectively). In the xenogeneic mouse model, rhTPO mitigated tissue pathology and modulated immune cell subsets. In vitro, rhTPO regulated PBMC proliferation and enhanced lymphocyte differentiation.

Conclusions

rhTPO may reduce the risk of aGVHD by modulating immune responses and protecting tissues, supporting its potential role as an adjunct therapy in allo-HSCT.

查看原文本刊更多论文

重组人血小板生成素降低急性移植物抗宿主病的风险及其机制。

目的：急性移植物抗宿主病（aGVHD）是同种异体造血干细胞移植（alloo - hsct）的严重并发症。本研究旨在通过回顾性临床数据和异种GVHD小鼠模型来评估重组人血小板生成素（rhTPO）对aGVHD的影响。方法：我们回顾性分析了2016年至2018年间接受同种异体移植的162例患者，比较了接受rhTPO治疗和未接受rhTPO治疗的患者的结果。此外，我们用接受同种异体pbmc的Balb/c小鼠建立了小鼠GVHD模型。用不同剂量的rhTPO处理小鼠，以评估器官病理、免疫细胞亚群和细胞因子表达。人pbmc也用rhTPO处理，以评估体外增殖和分化。结果以比值比（OR）表示，95% %置信区间（CI）， P为  ，0.05认为有统计学意义。所有实验重复3次。结果：临床分析显示，rhTPO的使用和患者年龄的增大与aGVHD发病率的降低独立相关（P = 0.007,P = 0.014）。在异种小鼠模型中，rhTPO减轻了组织病理并调节了免疫细胞亚群。在体外，rhTPO调节PBMC增殖，增强淋巴细胞分化。结论：rhTPO可能通过调节免疫反应和保护组织来降低aGVHD的风险，支持其作为异源造血干细胞移植辅助治疗的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Transplant immunology 医学-免疫学

CiteScore

2.10

自引率

13.30%

发文量

198

审稿时长

48 days

期刊介绍： Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.