Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells.
Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells.
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DOI：
10.1097/txd.0000000000000827
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发表时间：
2018-09
影响因子：
2.3
通讯作者：
Djamali A
中科院分区：
文献类型：
--
作者：
Zhang Z;Wilson NA;Chinnadurai R;Panzer SE;Redfield RR 3rd;Reese SR;Galipeau J;Djamali A
我们推测，间充质基质细胞(MSC)的免疫调节特性可能被考虑用于脱敏。分别于−第2、3、6、9、12天(预防)或14、17、20、23、26天(治疗组)尾静脉输注自体或异基因骨髓间充质干细胞0.5M(0.5M)、1M或2M细胞/剂量(共10组，每组6只)。4周后，联合分析显示，自体和异体骨髓间充质干细胞在降低供者特异性抗体(dnDSA，P<；0.001)方面同样有效。剂量-反应研究表明，中剂量(共5M)的MSCs对降低IgG1dnDSA、IgG1a、IgG2cdnDSA的效果最好(P≤0.0 1)。时程研究表明，预防和治疗策略在降低IgG1dnDSA方面同样有效(P≤0.0 1)。然而，个体分组分析表明，中等剂量(5M)的自体骨髓间充质干细胞治疗在降低IgG1dnDSA、IgG1a和IgG2cdnDSA方面最有效(P≤0.01)。本组患者治疗1周后dnDSA下降，脾和外周血单核细胞中调节性B细胞增多，脾、外周血单核细胞和骨髓中过渡性B细胞增多(均P<；0.05)。我们的研究结果表明，自体MSC可防止输血引起的致敏，并上调过渡性和调节性B细胞的表达。还需要进一步的研究来确定肾移植后这些变化的生物学相关性。
We hypothesized that immunomodulatory properties of mesenchymal stromal cells (MSC) may be considered for desensitization. Autologous or allogeneic bone marrow derived MSC were infused via tail vein at 0.5 M (0.5 × 106), 1 M, or 2 M cells/dose on days −2, 3, 6, 9, 12 (prevention) or 14, 17, 20, 23, 26 (treatment) relative to transfusion in a Brown Norway to Lewis rat model (10 groups total, n = 6 per group). At 4 weeks, pooled analyses demonstrated that autologous and allogeneic MSC were equally effective in reducing IgG1 and IgG2a de novo donor-specific antibody (dnDSA, P < 0.001). Dose-response studies indicated that moderate-dose MSC (5 M total) was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). Time course studies determined that preventive and treatment strategies were equally effective in reducing IgG1 and IgG2a dnDSA (P ≤ 0.01). However, individual group analyses determined that moderate-dose (5 M) treatment with autologous MSC was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). In this group, dnDSA decreased after 1 week of treatment; regulatory B cells increased in the spleen and peripheral blood mononuclear cells; and transitional B cells increased in the spleen, peripheral blood mononuclear cells, and bone marrow (P < 0.05 for all). Our findings indicate that autologous MSC prevent transfusion-elicited sensitization and upregulate transitional, and regulatory B cells. Additional studies are needed to determine the biological relevance of these changes after kidney transplantation.