Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Division of Nucleic Acid Drug Development, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan.
Transplant Proc. 2022 Sep;54(7):1998-2007. doi: 10.1016/j.transproceed.2022.05.038. Epub 2022 Aug 28.
Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model.
Subjects were divided into no treatment, tacrolimus administration, recipient ADMSC administration, donor ADMSC administration, and mixed donor and recipient ADMSC administration groups. ADMSC-administered groups were also treated with tacrolimus. Histologic study, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction were used for various analyses.
Fluorescently labeled ADMSCs were predominant in the grafted donor lung, but not in the recipient lung, on day 5. On day 7, the pathologic rejection grades of the grafted donor lung were significantly lower in the ADMSC-administered groups (P < .05) and did not differ among these groups. Although serum hepatocyte growth factor and vascular endothelial growth factor levels did not differ among the groups, interleukin 10 level was slightly higher in the ADMSC-administered groups. The numbers of infiltrating regulatory T cells in the grafted lung were significantly higher in the ADMSC-administered groups (P < .05) but did not differ with cell origin. Transcriptional analysis suggested interleukin 6 suppression to be the main overlapping immunosuppressive mechanism, regardless of origin. Therefore, a donor or recipient origin may not influence the immunosuppressive efficacy of ADMSCs in our rat lung transplantation model.
Collectively, the results indicate that allogenic ADMSCs, regardless of their origin, may exert similar immunosuppressive effects in clinical organ transplantation.
间充质干细胞（MSCs）在器官移植领域开始被证明具有免疫抑制作用。然而，MSC 来源（供体或受体）对免疫抑制的影响尚不清楚。因此，我们在大鼠肺移植模型中研究了受体和供体脂肪来源的间充质干细胞（ADMSCs）对免疫抑制的影响。
将研究对象分为未治疗组、他克莫司给药组、受体 ADMSC 给药组、供体 ADMSC 给药组和供体和受体 ADMSC 混合给药组。ADMSC 给药组也接受他克莫司治疗。采用组织学研究、免疫荧光、免疫组织化学、酶联免疫吸附试验和聚合酶链反应进行各种分析。
第 5 天，荧光标记的 ADMSCs 主要存在于移植的供体肺中，但不存在于受体肺中。第 7 天，ADMSC 给药组移植供体肺的病理排斥反应分级显著降低（P <.05），且组间无差异。虽然各组间血清肝细胞生长因子和血管内皮生长因子水平无差异，但 ADMSC 给药组白细胞介素 10 水平略高。移植肺中浸润的调节性 T 细胞数量在 ADMSC 给药组显著增加（P <.05），但与细胞来源无关。转录分析表明，无论起源如何，白细胞介素 6 抑制可能是主要的重叠免疫抑制机制。因此，在我们的大鼠肺移植模型中，供体或受体来源可能不会影响 ADMSC 的免疫抑制效果。
总之，这些结果表明，同种异体 ADMSCs 无论其来源如何，在临床器官移植中可能具有相似的免疫抑制作用。
