Recently, mesenchymal stem cells (MSCs) have been shown to have immunomodulatory properties which hold promise for their clinical use to treat inflammatory conditions. Relative to bone marrow-derived MSCs (BMSCs), which are typically isolated from the iliac crest, we have recently demonstrated that MSCs can be predictably isolated from the alveolar bone (aBMSCs) by less invasive means. As such, the aim of this study was to characterize the immunomodulatory properties of aBMSCs relative to BMSCs. aBMSCs isolated from the human alveolar bone and BMSCs isolated from the human bone marrow of the iliac crest were cultured in the same conditions. Cytokine arrays and enzyme-linked immunosorbent assays (ELISA) of a conditioned medium were used to evaluate differences in the secretion of cytokines. In different functional assays, aBMSCs and BMSCs were cocultured with different types of immune cells including THP-1 monocytes, macrophages, and peripheral blood mononuclear cells (PBMCs) to evaluate their effects on important immune cell functions including proliferation, differentiation, and activation. The protein arrays identified interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 to be the major cytokines secreted by aBMSCs and BMSCs. ELISA determined that aBMSCs secreted 268.64 ± 46.96 pg/mL of IL-6 and 196.14 ± 97.31 pg/mL of MCP-1 per microgram of DNA, while BMSCs secreted 774.86 ± 414.29 pg/mL of IL-6 and 856.37 ± 433.03 pg/mL of MCP-1 per microgram of DNA. The results of the coculture studies showed that aBMSCs exhibited immunosuppressive effects on monocyte activation and T cell activation and proliferation similar to BMSCs. Both aBMSCs and BMSCs drove macrophages into an anti-inflammatory phenotype with increased phagocytic ability. Taken together, these data suggest that aBMSCs have potent immunomodulatory properties comparable to those of BMSCs. The findings of this study have important implications for the development of immunomodulatory stem cell therapies aimed to treat inflammatory conditions using aBMSCs, a more feasible tissue source of MSCs.

中文翻译：

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肺泡骨源间充质干细胞的免疫调节特性的表征。

最近，间充质干细胞（MSCs）已显示具有免疫调节特性，有望在临床上用于治疗炎症。相对于通常从中分离的骨髓来源的MSC（BMSC），我们最近证明，可以通过侵入性较小的方法将MSC从肺泡骨（aBMSC）中分离出来。因此，本研究的目的是表征aBMSC相对于BMSC的免疫调节特性。在相同条件下培养从人牙槽骨分离的aBMSC和从the骨人骨髓分离的BMSC。条件培养基的细胞因子阵列和酶联免疫吸附测定（ELISA）用于评估细胞因子分泌的差异。在不同的功能测定中 将aBMSC和BMSC与不同类型的免疫细胞（包括THP-1单核细胞，巨噬细胞和外周血单核细胞（PBMC））共培养，以评估它们对重要免疫细胞功能（包括增殖，分化和激活）的影响。蛋白质阵列鉴定出白介素（IL）-6和单核细胞趋化蛋白（MCP）-1是aBMSC和BMSC分泌的主要细胞因子。ELISA法测定aBMSC每微克DNA分泌268.64±46.96 pg / mL IL-6和196.14±97.31 pg / mL MCP-1，而BMSC分泌IL-6 774.86±414.29 pg / mL和856.37±433.03 pg / mL每微克DNA毫升的MCP-1。共培养研究的结果表明，aBMSC与BMSC相似，对单核细胞激活以及T细胞激活和增殖均表现出免疫抑制作用。aBMSC和BMSC都将巨噬细胞驱动为具有吞噬能力增强的抗炎表型。综上所述，这些数据表明aBMSC具有与BMSC相当的有效免疫调节特性。这项研究的发现对于免疫调节干细胞疗法的发展具有重要意义，该疗法旨在使用aBMSCs（一种更可行的MSCs组织来源）治疗炎症。