Department of Chemistry and Environmental Science, New Jersey Institute of Technology (NJIT), Newark, NJ, 07102, USA.
Keenan and Li Ka Shing Knowledge Institute, University Health Toronto - St. Michael's Hospital, Toronto, Ontario, Canada.
Stem Cell Rev Rep. 2020 Oct;16(5):812-827. doi: 10.1007/s12015-020-10000-1.
Critical illnesses including sepsis, acute respiratory distress syndromes, ischemic cardiovascular disorders and acute organ injuries are associated with high mortality, morbidity as well as significant health care system expenses. While these diverse conditions require different specific therapeutic approaches, mesenchymal stem/stromal cell (MSCs) are multipotent cells capable of self-renewal, tri-lineage differentiation with a broad range regenerative and immunomodulatory activities, making them attractive for the treatment of critical illness. The therapeutic effects of MSCs have been extensively investigated in several pre-clinical models of critical illness as well as in phase I and II clinical cell therapy trials with mixed results. Whilst these studies have demonstrated the therapeutic potential for MSC therapy in critical illness, optimization for clinical use is an ongoing challenge. MSCs can be readily genetically modified by application of different techniques and tools leading to overexpress or inhibit genes related to their immunomodulatory or regenerative functions. Here we will review recent approaches designed to enhance the therapeutic potential of MSCs with an emphasis on the technology used to generate genetically modified cells, target genes, target diseases and the implication of genetically modified MSCs in cell therapy for critical illness.
包括脓毒症、急性呼吸窘迫综合征、缺血性心血管疾病和急性器官损伤在内的危重病与高死亡率、高发病率以及大量医疗保健系统支出相关。虽然这些不同的病症需要不同的特定治疗方法，但间充质干细胞（MSCs）是具有自我更新能力的多能细胞，能够向三系分化，并具有广泛的再生和免疫调节活性，使其成为治疗危重病的有吸引力的选择。MSC 在几种危重病的临床前模型中以及在 I 期和 II 期临床试验中的细胞治疗中进行了广泛的治疗效果研究，结果喜忧参半。虽然这些研究表明了 MSC 治疗在危重病中的治疗潜力，但优化用于临床应用是一个持续的挑战。可以通过应用不同的技术和工具来对 MSCs 进行基因修饰，从而导致与它们的免疫调节或再生功能相关的基因过表达或抑制。在这里，我们将回顾最近旨在增强 MSCs 治疗潜力的方法，重点介绍用于生成基因修饰细胞的技术、靶基因、靶疾病以及基因修饰 MSCs 在危重病细胞治疗中的意义。
