Table_2_Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury.docx

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.

在控制登革热疾病严重程度的临床研究方面已投入大量努力；然而，登革热的发病率与死亡率并未下降。登革热病毒（DENV）能够感染并导致多个器官的系统性损伤，进而引发器官衰竭。本研究提出了一种创新的基于干细胞的定制化治疗方案，该方案有助于病毒清除，并在登革热感染过程中挽救肝细胞免受进一步损伤。我们向感染DENV的BALB/c小鼠模型中输入了造血干细胞和内皮祖细胞混合物，并发现这种细胞混合物的输注改善了它们的肝功能，这一发现通过血液学、组织病理学和下一代测序得到了证实。这些干细胞和祖细胞能够分化为靶细胞，修复受损组织。此外，该治疗方案还能够调节内皮细胞的增殖和通透性，调节炎症反应，增强细胞外基质的生产和血管生成，并分泌一系列生长因子，从而为细胞的修复提供一个增强的环境。目前尚无关于使用干细胞组合治疗登革热感染的研究发表。综上所述，干细胞治疗成功地挽救了由登革热引起的肝脏损伤，在小鼠模型中减少了细胞凋亡，并改善了修复与再生过程。