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

S Sakinah,Xiaoyun Wu,Chenglong Xiong,Faizal Abu Bakar,Hui-Yee Chee,Mahendran Maniam,Pooi Ling Mok,Antony V Samrot,S Suresh Kumar,Zhong Sun,Guozhong He,Narcisse Joseph,Akon Higuchi,Badr Alzahrani,Rusheni Munisvaradass,Seoh Wei Teh,Rukman Awang Hamat,Jia Bei Tong,Sivan Padma Priya

doi:10.3389/fcell.2021.637270

Abstract

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.

Highlights

Dengue virus (DENV) infections transmitted by mosquitoes is setting half of the world’s population at risk
We show a novel therapeutic approach using a combination of stem cells [hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs)] to treat DENV infection and rescue clinical outcome and dengue-induced liver injury in an animal model
The findings demonstrate that the use of combination stem cell therapy cannot only heal vascular injury, thrombocytopenia, and hepatocyte damage caused by DENV and reduce the presence of DENV in the liver tissue, suggesting clearance of DENV

Summary

INTRODUCTION

Dengue virus (DENV) infections transmitted by mosquitoes is setting half of the world’s population at risk. We show a novel therapeutic approach using a combination of stem cells [hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs)] to treat DENV infection and rescue clinical outcome and dengue-induced liver injury in an animal model. The focal points studied were changes in the state of the animals, clinical profiles, histopathology, and next-generation sequencing (NGS) of each liver gene expressed in the control, DENV-infected (DVI), and stem-cells-treated (DVI-SCT) groups. The therapeutic efficacy of stem cells against viral infection was evaluated by observing and examining several physical parameters, including behavioral changes exhibited by the experimental animals, clinical profile parameters (i.e., platelet, white blood cell, red blood cell counts, and lymphocyte, and hemoglobin levels), histopathological changes, and NGS data. The findings demonstrate that the use of combination stem cell therapy cannot only heal vascular injury, thrombocytopenia, and hepatocyte damage caused by DENV and reduce the presence of DENV in the liver tissue, suggesting clearance of DENV

RESULTS AND DISCUSSION

MATERIALS AND METHODS

ETHICS STATEMENT