Department of Immunology, Leiden University Medical Center, Leiden University, Leiden, Netherlands.
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
Front Immunol. 2024 Oct 9;15:1455300. doi: 10.3389/fimmu.2024.1455300. eCollection 2024.
Infusion of mesenchymal stromal cells (MSCs) has been proposed as immune-modulatory therapy in solid organ transplantation. The use of allogenic MSCs could improve standardization and allow for direct availability of the product.
The nonrandomized phase Ib Neptune clinical trial provided safety and feasibility data on the use of allogenic bone-marrow-derived MSCs, infused in 10 patients at week 25 and 26 post kidney transplantation. Here, we performed detailed analysis on the peripheral blood immune cell composition of these patients up to 52 weeks post transplantation. We used a 40 marker antibody panel with mass cytometry to assess potential effects of MSC therapy on the immune system.
We showed minor changes in major immune lineages at week 27, 34 and 52 post kidney transplantation after MSC infusion at week 25 and week 26, confirming previous data with regular flow cytometry. However, in a direct comparison between pre- and post MSC infusion, as soon as 4 hours after MSC infusion, we observed a significant increase in cell numbers of B cell and T cell subsets that shared a unique expression of CD11b, CD11c, CD38, CD39, and Ki-67.
Exploring these CD11bCD11cCD38CD39Ki-67 B cells and T cells in the context of MSC infusion after kidney transplantation may be a promising avenue to better understand the immunological effects of MSC therapy.
间充质基质细胞(MSCs)输注被提议作为实体器官移植中的免疫调节疗法。使用同种异体 MSCs 可以提高标准化程度,并允许直接获得产品。
非随机的 Neptune 临床研究 Ib 期提供了在肾移植后第 25 周和第 26 周输注同种异体骨髓来源 MSCs 的安全性和可行性数据。在这里,我们对这些患者在移植后 52 周内的外周血免疫细胞组成进行了详细分析。我们使用带有质谱流式细胞术的 40 个标记抗体面板来评估 MSC 治疗对免疫系统的潜在影响。
我们显示在 MSC 输注后第 25 周和第 26 周,在肾移植后第 27、34 和 52 周时,主要免疫谱系发生了轻微变化,这证实了之前使用常规流式细胞术获得的数据。然而,在 MSC 输注前后的直接比较中,在 MSC 输注后 4 小时,我们观察到 B 细胞和 T 细胞亚群的细胞数量显著增加,这些亚群共同表达 CD11b、CD11c、CD38、CD39 和 Ki-67。
在肾移植后 MSC 输注的背景下探索这些 CD11bCD11cCD38CD39Ki-67 B 细胞和 T 细胞可能是更好地理解 MSC 治疗免疫效应的有前途的途径。