Table_1_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.

在防控登革热疾病的严重程度方面，临床研究投入了大量的努力；然而，登革热的发病率与死亡率并未有所下降。登革病毒（DENV）能够感染多种器官并导致系统性损伤，进而引发器官衰竭。在本研究中，我们提出了一项创新的基于干细胞的治疗方案，该方案有助于病毒清除并在登革热感染过程中拯救受损的肝细胞。我们在感染登革病毒的BALB/c小鼠模型中使用了造血干细胞和内皮祖细胞组合治疗，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并修复受损的组织。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，以创造一个有利于细胞修复的增强环境。迄今为止，尚未有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损伤，在小鼠模型中表现出更低的细胞凋亡率以及改善的修复和再生能力。