Faculty of Dentistry, National University of Singapore, Singapore; Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore.
Institute of Medical Biology, Agency for Science, Technology and Research, Singapore.
Cytotherapy. 2018 Dec;20(12):1419-1426. doi: 10.1016/j.jcyt.2018.09.008. Epub 2018 Oct 20.
Mesenchymal stromal cell (MSC) therapies have demonstrated therapeutic efficacy in a wide-ranging array of tissue injury and disease indications. An important aspect of MSC-mediated therapeutic activities is immune modulation. Consistent with the concentration of MSC therapeutic potency in its secretion, a significant proportion of MSC immune potency resides in the small extracellular vesicles (sEVs) secreted by MSCs. These sEVs, which also include exosomes, carry a large cargo enriched in proteins with potent immunomodulatory activities. They have been reported to exert potent effects on humoral and cellular components of the immune system in vitro and in vivo, and may have the potential to support the diametrically opposite pro- and anti-inflammatory functions necessary for tissue repair and regeneration following injury. Following injury, pro-inflammatory activities are necessary to neutralize injury and remove dead or injured tissue, while anti-inflammatory activities to facilitate migration and proliferation of reparative cell types and to increase vascularization and nutrient supply are necessary to repair and regenerate new tissue. Therefore, a critical immunomodulatory requisite of MSC sEVs in tissue regeneration is the capacity to support the appropriate immune activities at the appropriate time. Here, we review how some of the immune regulatory targets of MSC sEVs could support the dynamic immunomodulatory activities during tissue repair and regeneration.
间充质基质细胞 (MSC) 疗法在广泛的组织损伤和疾病适应症中显示出治疗效果。MSC 介导的治疗活性的一个重要方面是免疫调节。与 MSC 治疗效力在其分泌中的浓度一致，MSC 免疫效力的很大一部分存在于 MSC 分泌的小细胞外囊泡 (sEVs) 中。这些 sEVs 还包括外泌体，携带大量富含具有强大免疫调节活性的蛋白质的货物。据报道，它们在体外和体内对免疫系统的体液和细胞成分具有强大的作用，并且可能具有支持损伤后组织修复和再生所需的截然相反的促炎和抗炎功能的潜力。损伤后，需要促炎活性来中和损伤并清除死亡或受损组织，而需要抗炎活性来促进修复细胞类型的迁移和增殖，并增加血管生成和营养供应，以修复和再生新组织。因此，MSC sEV 在组织再生中的关键免疫调节要求是能够在适当的时间支持适当的免疫活性。在这里，我们回顾了 MSC sEV 的一些免疫调节靶标如何支持组织修复和再生过程中的动态免疫调节活性。
