Dose- and Time-Dependent Effects of Human Mesenchymal Stromal Cell Infusion on Cardiac Allograft Rejection in Mice
Dose- and Time-Dependent Effects of Human Mesenchymal Stromal Cell Infusion on Cardiac Allograft Rejection in Mice
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人间充质基质细胞输注对小鼠心脏同种异体移植排斥的剂量和时间依赖性影响
DOI：
10.1089/scd.2019.0300
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Longshan Liu
中科院分区：
文献类型：
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作者：
Feng Wang;Xiaoyong Chen;Jun Li;Dong Wang;Huiting Huang;Xirui Li;Zirong Bi;Yanwen Peng;Xiaoran Zhang;Gang Li;Jiali Wang;Changxi Wang;Qian Fu;Longshan Liu
心脏移植是许多终末期心脏病的最终挽救生命的治疗策略。需要长期的免疫抑制方案来预防同种异体移植排斥反应。骨髓间充质干细胞（MSC）已被证明是器官移植的免疫调节治疗。然而，MSC治疗的剂量和时间对心脏移植的影响尚未得到研究。在本研究中，我们在接受C57 BL/6心脏移植前（7天或24小时）或后（24小时）向受体BALB/c小鼠输注了三种剂量（1 × 106、2 × 106和5 × 106个细胞）的人MSCs（hMSCs）。结果发现，移植后24 h输注高剂量hMSCs（5 × 106）可明显延长移植心脏的存活时间。为了描述潜在的机制，采集移植物、脾和引流淋巴结进行分析。hMSC处理的剂量依赖性效应显示为：（1）移植物中国际心肺移植学会（ISHLT）评分的减轻;（2）CD 4+和CD 8 +T细胞的群体的减少;（3）调节性T（Treg）细胞的增加;（4）炎性细胞因子和供体特异性抗体的血清水平的降低。总之，我们在小鼠心脏移植模型中显示了hMSC治疗对急性同种异体移植排斥反应的时间关键性和剂量依赖性免疫调节作用。
Heart transplantation is the final life-saving therapeutic strategy for many end-stage heart diseases. Long-term immunosuppressive regimens are needed to prevent allograft rejection. Mesenchymal stromal cells (MSCs) have been shown as immunomodulatory therapy for organ transplantation. However, the effect of dose and timing of MSC treatment on heart transplantation has not yet been examined. In this study, we infused three doses (1 × 106, 2 × 106, or 5 × 106cells) of human MSCs (hMSCs) to the recipient BALB/c mice before (7 days or 24 h) or after (24 h) receiving C57BL/6 cardiac transplants. We found that infusion of high dose hMSCs (5 × 106) at 24 h post-transplantation significantly prolonged the survival time of cardiac grafts. To delineate the underlying mechanism, grafts, spleens, and draining lymph nodes were harvested for analysis. Dose-dependent effect of hMSC treatment was shown in: (1) alleviation of International Society of Heart and Lung Transplantation (ISHLT) score in grafts; (2) reduction of the population of CD4+and CD8+T cells; (3) increase of regulatory T (Treg) cells; (4) and decrease of serum levels of inflammatory cytokines and donor-specific antibodies. Taken together, we showed timing critical and dose-dependent immunomodulatory effects of hMSC treatment against acute allograft rejection in a mouse model of heart transplantation.