Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review.
Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review.
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DOI：
10.3389/fcell.2020.587776
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发表时间：
2020
影响因子：
5.5
通讯作者：
Oceandy D
中科院分区：
文献类型：
--
作者：
Pawitan JA;Bui TA;Mubarok W;Antarianto RD;Nurhayati RW;Dilogo IH;Oceandy D
间充质干细胞(又称间充质基质细胞/MSCs)的治疗能力取决于它们通过分泌有益的旁分泌因子来响应受损组织的需要的能力。MSCs可以通过基因工程来表达某些有益的因素。这项系统性综述的目的是汇编和分析已发表的科学文献，这些文献报道了利用工程MSCs治疗各种疾病/状况，讨论其作用机制，并评估工程MSC治疗的疗效。计算机检索PubMed/MEDLINE和Cochrane图书馆于2019年7月27日发表的所有研究，无时间限制，检索词为“Engineering MSC”和“Treatment”或“Maniped MSC”和“Treatment”。此外，还添加了在全文搜索过程中找到的相关文章。我们确定了85篇在本文中进行综述的文章。在85篇综述文章中，51篇研究报告了使用工程MSCs治疗肿瘤/癌症/恶性肿瘤/转移，而其他34篇研究测试了工程MSCs用于治疗非肿瘤疾病。大多数研究报告了MSCs在动物模型中的使用，只有一项研究报告了在人类受试者中的试验。39项研究表明，表达有益的旁分泌因子将显著提高MSCs的治疗效果，33项研究显示效果中等，1项人类研究报告没有效果。以间充质干细胞为基础的癌症治疗的作用机制包括表达“自杀基因”、诱导肿瘤细胞凋亡以及传递细胞因子以诱导对癌细胞的免疫反应。在非癌症疾病的治疗方面，在综述的论文中描述的机制包括血管生成、成骨和生长因子的表达。通过基因修饰诱导某些旁分泌因子的表达，可增强MSCs的治疗能力。基因工程MSCs已经成功地应用于各种疾病的动物模型。然而，应该谨慎地解释这一结果，因为动物模型可能不能完美地代表真实的人类疾病。因此，需要进一步的研究来探索基因工程MSCs的翻译潜力。
The therapeutic capacity of mesenchymal stem cells (also known as mesenchymal stromal cells/MSCs) depends on their ability to respond to the need of the damaged tissue by secreting beneficial paracrine factors. MSCs can be genetically engineered to express certain beneficial factors. The aim of this systematic review is to compile and analyze published scientific literatures that report the use of engineered MSCs for the treatment of various diseases/conditions, to discuss the mechanisms of action, and to assess the efficacy of engineered MSC treatment. We retrieved all published studies in PubMed/MEDLINE and Cochrane Library on July 27, 2019, without time restriction using the following keywords: “engineered MSC” and “therapy” or “manipulated MSC” and “therapy.” In addition, relevant articles that were found during full text search were added. We identified 85 articles that were reviewed in this paper. Of the 85 articles reviewed, 51 studies reported the use of engineered MSCs to treat tumor/cancer/malignancy/metastasis, whereas the other 34 studies tested engineered MSCs in treating non-tumor conditions. Most of the studies reported the use of MSCs in animal models, with only one study reporting a trial in human subjects. Thirty nine studies showed that the expression of beneficial paracrine factors would significantly enhance the therapeutic effects of the MSCs, whereas thirty three studies showed moderate effects, and one study in humans reported no effect. The mechanisms of action for MSC-based cancer treatment include the expression of “suicide genes,” induction of tumor cell apoptosis, and delivery of cytokines to induce an immune response against cancer cells. In the context of the treatment of non-cancerous diseases, the mechanism described in the reviewed papers included the expression of angiogenic, osteogenic, and growth factors. The therapeutic capacity of MSCs can be enhanced by inducing the expression of certain paracrine factors by genetic modification. Genetically engineered MSCs have been used successfully in various animal models of diseases. However, the results should be interpreted cautiously because animal models might not perfectly represent real human diseases. Therefore, further studies are needed to explore the translational potential of genetically engineered MSCs.
影响因子：
5.2
作者：
Frank, Richard T.;Najbauer, Joseph;Aboody, Karen S.
通讯作者：
Aboody, Karen S.