Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea.
Department of Medicine, Institute for Stem Cell Biology and Regenerative Medicine, and Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Sci Rep. 2017 Jan 13;7:39593. doi: 10.1038/srep39593.
Mesenchymal stem cells (MSCs) have multiple properties including anti-inflammatory and immunomodulatory effects in various disease models and clinical treatments. These beneficial effects, however, are sometimes inconsistent and unpredictable. For wider and proper application, scientists sought to improve MSC functions by engineering. We aimed to invent a novel method to produce synthetic biological drugs from engineered MSCs. We investigated the anti-arthritic effect of engineered MSCs in a collagen-induced arthritis (CIA) model. Biologics such as etanercept are the most successful drugs used in anti-cytokine therapy. Biologics are made of protein components, and thus can be theoretically produced from cells including MSCs. MSCs were transfected with recombinant minicircles encoding etanercept (trade name, Enbrel), which is a tumour necrosis factor α blocker currently used to treat rheumatoid arthritis. We confirmed minicircle expression in MSCs in vitro based on GFP. Etanercept production was verified from the conditioned media. We confirmed that self-reproduced etanercept was biologically active in vitro. Arthritis subsided more efficiently in CIA mice injected with mcTNFR2MSCs than in those injected with conventional MSCs or etanercept only. Although this novel strategy is in a very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics and engineering MSCs.
间充质干细胞（MSCs）具有多种特性，包括在各种疾病模型和临床治疗中具有抗炎和免疫调节作用。然而，这些有益的效果有时是不一致和不可预测的。为了更广泛和正确地应用，科学家们试图通过工程改造来提高 MSC 的功能。我们旨在发明一种从工程 MSC 中生产合成生物药物的新方法。我们研究了工程 MSC 在胶原诱导性关节炎（CIA）模型中的抗关节炎作用。依那西普等生物制剂是抗细胞因子治疗中最成功的药物。生物制剂由蛋白质成分组成，因此理论上可以从包括 MSC 在内的细胞中生产。我们用编码依那西普（商品名：Enbrel）的重组微小环转染 MSC，依那西普是一种目前用于治疗类风湿关节炎的肿瘤坏死因子-α阻断剂。我们根据 GFP 确认了 MSC 中微小环的表达。从条件培养基中验证了依那西普的产生。我们证实了在体外，自我复制的依那西普具有生物活性。与注射常规 MSC 或仅注射依那西普的 CIA 小鼠相比，注射 mcTNFR2MSCs 的小鼠关节炎消退得更有效。尽管这种新策略处于非常早期的概念阶段，但它似乎代表了生物制剂和工程 MSC 传递的一种潜在替代方法。
