Wu Peipei, Wang Zhangfei, Sun Yongping, Cheng Zhixiang, Wang Min, Wang Baolong
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Core Unit of National Clinical Research Center for Laboratory Medicine, Hefei, China.
J Nanobiotechnology. 2025 Mar 26;23(1):251. doi: 10.1186/s12951-025-03297-y.
Graft-versus-host disease (GvHD) is a prevalent complication following allogeneic hematopoietic stem cell transplantation (HSCT) and is characterized by relatively high morbidity and mortality rates. GvHD can result in extensive systemic damage in patients following allogeneic HSCT (allo-HSCT), with the skin, gastrointestinal tract, and liver frequently being the primary target organs affected. The severe manifestations of acute intestinal GvHD often indicate a poor prognosis for patients after allo-HSCT. Endoscopy and histopathological evaluation remain employed to diagnose GvHD, and auxiliary examinations exclude differential diagnoses. Currently, reliable serum biomarkers for the diagnosis and differential diagnosis of GvHD are scarce. As an essential part of standard transplant protocols, early application of immunosuppressive drugs effectively prevents GvHD. Among them, steroids represent first-line therapeutic agents, and the JAK2 inhibitor ruxolitinib represents the second-line therapeutic agent. Currently, no efficacious treatment modality exists for steroid-resistant aGvHD. Therefore, the diagnosis and treatment of GvHD still face significant medical demands. Extracellular vesicles (EVs) are nanometer to micrometer-scale biomembrane vesicles containing various bioactive components, such as proteins, nucleotides, and metabolites. Distinctive changes in serum-derived EV components occur in patients after allo-HSCT; Hence, EVs are expected to be potential biomarkers for diagnosing and treating GvHD. Furthermore, cell-free therapeutics characterized by EVs derived from mesenchymal stem cells (MSCs) have manifested remarkable therapeutic efficacy in preclinical models and preclinical trials of GvHD. Customized engineered EVs with fewer toxic and side effects for the combined treatment of GvHD hold broad prospects for clinical translation. This review article examines the potential value of translating EVs into clinical applications for the diagnosis and treatment of GvHD. It summarizes the latest advancements and prospects of engineered EVs applying GvHD.
移植物抗宿主病（GvHD）是异基因造血干细胞移植（HSCT）后常见的并发症，其特点是发病率和死亡率相对较高。GvHD可导致异基因HSCT（allo-HSCT）患者出现广泛的全身损伤，皮肤、胃肠道和肝脏常为主要受累靶器官。急性肠道GvHD的严重表现往往提示allo-HSCT患者预后不良。目前仍采用内镜检查和组织病理学评估来诊断GvHD，并通过辅助检查排除鉴别诊断。目前，用于GvHD诊断和鉴别诊断的可靠血清生物标志物稀缺。作为标准移植方案的重要组成部分，早期应用免疫抑制药物可有效预防GvHD。其中，类固醇是一线治疗药物，JAK2抑制剂芦可替尼是二线治疗药物。目前，对于类固醇耐药的急性GvHD尚无有效的治疗方法。因此，GvHD的诊断和治疗仍面临巨大的医学需求。细胞外囊泡（EVs）是纳米到微米级的生物膜囊泡，含有各种生物活性成分，如蛋白质、核苷酸和代谢产物。allo-HSCT患者血清来源的EV成分会发生明显变化；因此，EVs有望成为诊断和治疗GvHD的潜在生物标志物。此外，以间充质干细胞（MSCs）来源的EV为特征的无细胞疗法在GvHD的临床前模型和临床试验中已显示出显著的治疗效果。定制的工程化EVs对GvHD联合治疗的毒副作用较小，具有广阔的临床转化前景。本文综述探讨了将EVs转化为GvHD诊断和治疗临床应用的潜在价值。总结了应用GvHD的工程化EVs的最新进展和前景。
