de Andrade Ana Valéria Gouveia, Riewaldt Julia, Wehner Rebekka, Schmitz Marc, Odendahl Marcus, Bornhäuser Martin, Tonn Torsten
Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany.
J Cell Mol Med. 2014 Jun;18(6):1184-93. doi: 10.1111/jcmm.12264. Epub 2014 Mar 21.
Mesenchymal stromal cells (MSCs) are promising candidates for the treatment of graft-versus-host and autoimmune diseases. Here, by virtue of their immunosuppressive effects, they are discussed to exhibit inhibitory actions on various immune effector cells, including T lymphocytes that promote the underlying pathology. While it becomes apparent that MSCs exhibit their therapeutic effect in a transient manner, they are usually transplanted from third party donors into heavily immunocompromised patients. However, little is known about potential late complications of persisting third party MSCs in these patients. We therefore analysed the effect of gamma irradiation on the potency and proliferation of MSCs to elucidate an irradiation dose, which would allow inhibition of MSC proliferation while at the same time preserving their immunosuppressive function. Bone marrow-derived MSCs (BM-MSCs) were gamma-irradiated at increasing doses of 5, 10 and 30 Gy and subsequently assessed by colony formation unit (CFU)-assay, Annexin V-staining and in a mixed lymphocyte reaction, to assess colony growth, apoptosis and the immunosuppressive capacity, respectively. Complete loss of proliferative capacity measured by colony formation was observed after irradiation with a dose equal to or greater than 10 Gy. No significant decrease of viable cells was detected, as compared to non-irradiated BM-MSCs. Notably, irradiated BM-MSCs remained highly immunosuppressive in vitro for at least 5 days after irradiation. Gamma irradiation does not impair the immunosuppressive capacity of BM-MSCs in vitro and thus might increase the safety of MSC-based cell products in clinical applications.
间充质基质细胞（MSCs）是治疗移植物抗宿主病和自身免疫性疾病的有前景的候选细胞。在此，鉴于其免疫抑制作用，人们讨论了它们对各种免疫效应细胞的抑制作用，包括促进潜在病理过程的T淋巴细胞。虽然很明显MSCs以短暂的方式发挥其治疗作用，但它们通常是从第三方供体移植到严重免疫受损的患者体内。然而，对于这些患者中持续存在的第三方MSCs的潜在晚期并发症知之甚少。因此，我们分析了γ射线照射对MSCs效力和增殖的影响，以阐明一种照射剂量，该剂量既能抑制MSCs增殖，同时又能保留其免疫抑制功能。将骨髓来源的MSCs（BM-MSCs）分别用5、10和30 Gy的递增剂量进行γ射线照射，随后通过集落形成单位（CFU）测定、膜联蛋白V染色以及混合淋巴细胞反应进行评估，分别以评估集落生长、细胞凋亡和免疫抑制能力。在用等于或大于10 Gy的剂量照射后，通过集落形成测量的增殖能力完全丧失。与未照射的BM-MSCs相比，未检测到活细胞的显著减少。值得注意的是，照射后的BM-MSCs在体外照射后至少5天内仍保持高度免疫抑制作用。γ射线照射不会损害BM-MSCs在体外的免疫抑制能力，因此可能会提高基于MSCs的细胞产品在临床应用中的安全性。
