目的:人胎盘来源的蜕膜基质细胞(DSC)是新引入的基质细胞,已成功用于多项临床试验,用于治疗急性炎症性疾病。尽管发表了有关DSC的数据,需要更深入地探索与其他免疫细胞的作用机制和串扰。
方法:在混合淋巴细胞培养(MLC)中,使用有丝分裂原(伴刀豆球蛋白A)刺激Balb/c或B6小鼠的脾细胞,与人外周血单核细胞的同种异体(B6或Balb/c脾细胞)或异种激活。
结果:当10%的小鼠骨髓来源的MSC,是自体的,同种异体或单倍体(来自F1),被添加,观察到>95%的抑制。使用人(h)-DSC,当用于小鼠MLC的有丝分裂原和同种异体环境时,作为异种免疫调节细胞的抑制能力中位数为68%.然而,当人外周血单核细胞用作小鼠脾细胞(异种MLC)的刺激物时,hDSC显示88%的中值抑制。我们探索了单核细胞在基质细胞免疫调节功能中的存在和功能。CD14+单核细胞通过hDSC降低免疫抑制作用。hDSC对白细胞介素-2的自然杀伤细胞活化和增殖没有任何抑制作用。相反,DSC增加自然杀伤增殖的中值为58%。新鲜或冻融的hDSC在体外对人T细胞增殖(同种异体刺激和促分裂原刺激)具有相似的抑制作用。使用新鲜或冻融的DSC在室温下24小时期间的细胞活力相似。
结论:总而言之,组织相容性和CD14+单核细胞对hDSC免疫调节有影响,但冻融或新鲜制备的细胞没有影响。
Human placenta-derived decidua stromal cells (DSCs) are newly introduced stromal cells that have successfully been used in several clinical trials for the treatment of acute inflammatory diseases. Despite published data about DSCs, deeper exploration of mechanisms of action and crosstalk with other immune cells need to be explored.
In mixed lymphocyte culture (MLC), the splenocytes from Balb/c or B6 mice were stimulated using mitogen (concanavalin A), allogeneic (B6 or Balb/c splenocytes) or xenogeneic activation with human peripheral blood mononuclear cells.
When 10% of the mouse bone marrow-derived-MSC, being autologous, allogeneic or haploidentical (from F1), was added, >95% inhibition was seen. Using human (h)-DSCs, the inhibitory capacity was a median 68% as a xenogeneic immunomodulatory cell when used in mitogen and allogeneic setting in mice MLC. However, when human peripheral blood mononuclear cells were used as stimulator for mouse splenocyte (xenogeneic MLC), hDSC showed a median inhibition of 88%. We explored the presence and function of monocytes in the immunomodulatory function of stromal cells. CD14+ monocyte cells reduced the immunosuppressive effect by hDSC. hDSCs did not show any inhibitory effect on natural killer cell activation and proliferation by interleukin-2. In contrast DSCs increased natural killer proliferation by a median of 58%. Fresh or frozen-thawed hDSCs had similar inhibitory effects on human T-cell proliferation (both allo-stimulation and mitogen stimulation) in vitro. Cell viability at room temperature during 24 h was similar using fresh or freeze-thawed DSCs.
To conclude, histocompatibility and CD14+ monocyte cells had an impact on hDSC immunomodulation but frozen-thawed or freshly prepared cells did not.