Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Department of Parasitology & Immunopathoetiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Transpl Immunol. 2019 Aug;55:101205. doi: 10.1016/j.trim.2019.03.004. Epub 2019 Apr 1.
Graft-versus-host disease (GVHD) constitutes the most frequent complications after the allogeneic hematopoietic stem cell transplantation for a variety of hematological malignancies. In the present study, we explored the prophylactic potential of adipose tissue-derived mesenchymal stem cells (AD-MSCs) in controlling GVHD in murine models with a special focus on bone marrow aplasia related with acute GVHD. The CB6F1 mice were induced GVHD by the injection intravenously of C57BL/6 (B6-Ly-5.1) splenocytes without conditioning irradiation or chemotherapy. AD-MSCs from C3H mice were injected intravenously via tail veins. GVHD was assessed using flowcytometry analysis of peripheral blood cells and histopathologic analysis of target organs. Histopathological analyses revealed that AD-MSCs markedly suppressed the infiltration of lymphocytes into liver as well as the aplasia in bone marrow. This study is the first to clarify the effectiveness of AD-MSCs against bone marrow aplasia in GVHD, supporting a rationale of AD-MSCs for ameliorating bone marrow suppression and infectivity after allo-HSCT in human clinics.
移植物抗宿主病（GVHD）是异基因造血干细胞移植治疗多种血液系统恶性肿瘤后最常见的并发症之一。在本研究中，我们探讨了脂肪组织来源的间充质干细胞（AD-MSCs）在控制小鼠模型 GVHD 中的预防作用，特别是针对与急性 GVHD 相关的骨髓再生障碍。通过静脉注射 C57BL/6（B6-Ly-5.1）脾细胞而不进行条件照射或化疗，诱导 CB6F1 小鼠发生 GVHD。通过尾静脉静脉注射 C3H 小鼠的 AD-MSCs。通过流式细胞术分析外周血细胞和靶器官的组织病理学分析来评估 GVHD。组织病理学分析表明，AD-MSCs 显著抑制了淋巴细胞浸润肝脏以及骨髓再生障碍。这项研究首次阐明了 AD-MSCs 对 GVHD 中骨髓再生障碍的有效性，为 AD-MSCs 在改善同种异体 HSCT 后骨髓抑制和感染的临床应用提供了理论依据。
