Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice.

Meijuan Song,Peixin Xiao,Xiuwei Zhang,Shuli Sun,Shike Hou,Zhiguang Sun,Juan Cao,Man Tian,Qi Lv,Jinqiang Wang,Hui Ding,Wenlong Dong,Xue Wang,Ziquan Liu,Haojun Fan

doi:10.1155/2016/1691856

Abstract

Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs) for treatment of acute lung injury (ALI). However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs) in NOD/SCID mice with smoke inhalation injury (SII) through bioluminescence imaging (BLI). The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-α in BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells.

Highlights

Smoke inhalation injury (SII) is caused by smoke-induced damage of the respiratory tract and lung parenchyma, with or without additional heat-induced damage
Our results found that systemic treatment with human MSCs (hMSCs) could significantly decrease the levels of TNF-α in BAL fluid (BALF) (Figure 7(b)), which may contribute to downregulating inflammatory responses and tissue injury
acute lung injury (ALI) is a severe pathological condition clinically characterized by respiratory distress, refractory hypoxemia, and noncardiogenic pulmonary edema

Summary

Introduction

Smoke inhalation injury (SII) is caused by smoke-induced damage of the respiratory tract and lung parenchyma, with or without additional heat-induced damage. Stem Cells International into multiple different mesodermal lineages It has been shown in many different animal models that MSCs have a remarkable ability to localize to sites of injury and exert nonimmunogenic and immunosuppressive characteristics [8, 9]. Many studies have indicated that MSCs exert protective effects against ALI via their secretion of multiple paracrine factors, including endothelial and epithelial growth factors, anti-inflammatory cytokines, and antimicrobial peptides [17,18,19,20]. These studies have mainly focused on endotoxin-induced ALI, and researches focusing on the effects of MSCs on smoke inhalation-induced ALI still lack. Our results provide experimental support for the use MSCs to treat SII

Materials and Methods

Results

Findings

Discussion