Institute of Cellular Biology and Pathology "Nicolae Simionescu", 050568 Bucharest, Romania.
Int J Mol Sci. 2020 Dec 31;22(1):348. doi: 10.3390/ijms22010348.
Mesenchymal stromal cells (MSC) display several mechanisms of action that may be harnessed for therapeutic purposes. One of their most attractive features is their immunomodulatory activity that has been extensively characterized both in vitro and in vivo. While this activity has proven to be very efficient, it is transient. We aimed to enhance it by transforming MSC to overexpress a first apoptosis signal (Fas) ligand (FasL). In this study, our goal was to induce FasL overexpression through adenoviral transduction in MSC to improve their immunomodulatory activity. We characterized the impact of FasL overexpression on the morphology, proliferation, viability, phenotype, multilineage differentiation potential and immunomodulation of MSC. Moreover, we determined their suppressive properties in mixed reactions with A20 cells, as well as with stimulated splenocytes. Our findings demonstrate that FasL-overexpressing MSC exhibit improved immunosuppressive properties, while maintaining their MSC-characteristic features. In conclusion, we establish, in a proof-of-concept set-up, that FasL-overexpressing MSC represent good candidates for therapeutic intervention targeted at autoimmune disorders.
间充质基质细胞（MSC）表现出多种可能用于治疗目的的作用机制。它们最吸引人的特征之一是其免疫调节活性，这种活性已经在体外和体内得到了广泛的研究。虽然这种活性被证明非常有效，但它是短暂的。我们旨在通过将 MSC 转化为过表达第一凋亡信号（Fas）配体（FasL）来增强其活性。在这项研究中，我们的目标是通过腺病毒转导诱导 MSC 中 FasL 的过表达，以提高其免疫调节活性。我们描述了 FasL 过表达对 MSC 形态、增殖、活力、表型、多系分化潜能和免疫调节的影响。此外，我们还确定了它们在与 A20 细胞以及与刺激的脾细胞的混合反应中的抑制特性。我们的研究结果表明，过表达 FasL 的 MSC 表现出改善的免疫抑制特性，同时保持其 MSC 特征。总之，我们在概念验证设置中证明，过表达 FasL 的 MSC 是针对自身免疫性疾病的治疗干预的良好候选物。
