Chicken bone marrow mesenchymal stem cells improve lung and distal organ injury

Hanan Song,Hexuan Niu,Ruili Niu,Yuhan Guan,Xishuai Wang,Wenzaixiang Yan,Weijun Guan,Cong Liu,Shiyu Zhao,Xianchun Zong

doi:10.1038/s41598-021-97383-4

Abstract

Mesenchymal stem cells (MSCs) are associated with pulmonary protection and longevity. We separated chicken bone marrow-derived mesenchymal stem cells (BM-MSCs); investigated whether BM-MSCs can improve lipopolysaccharide (LPS)-induced lung and distal organ injury; and explored the underlying mechanisms. Ninety-six male ICR (6 weeks old) mice were randomly divided into three groups: Sham, LPS, and LPS + MSC groups. The mice were intratracheally injected with 5 mg/kg LPS to induce acute lung injury (ALI). The histopathological severity of injury to the lung, liver, kidney, heart, and aortic tissues was detected. Wet/dry ratio, protein concentrations in bronchoalveolar lavage fluid (BALF), BALF cell counts, inflammatory cytokine levels in serum, inflammatory cytokine gene expression, and oxidative stress-related indicators were detected. In addition, a survival analysis was performed in sixty male ICR mice (6 weeks old, 18–20 g). This study used chicken BM-MSCs, which are easier to obtain and more convenient than other animal or human MSCs, and have MSC-associated properties, such as a colony forming ability, multilineage differentiation potential, and certain phenotypes. BM-MSCs administration significantly improved the survival rate, systemic inflammation, and the histopathological severity of lung, liver, kidney, and aortic injury during ALI. BM-MSCs administration reduced the levels of inflammatory factors in BALF, the infiltration of neutrophils, and oxidative stress injury in lung tissue. In addition, BM-MSCs administration reduced TRL4 and Mdy88 mRNA expression during ALI. Chicken BM-MSCs serve as a potential alternative resource for stem cell therapy and exert a prominent effect on LPS-induced ALI and extrapulmonary injury, in part through TRL4/Mdy88 signaling and inhibition of neutrophil inflammation and oxidative stress injury.

Highlights

Led to an excessive inflammatory response via TLR4/MyD88 signaling, but the effects of BM-MSCs on TLR4/ MyD88 signaling are unclear
We aimed to identify whether BM-MSCs can prevent Acute lung injury (ALI) and distal organ injury
After culture under osteogenic induction conditions for 21 days, many calcium nodules appeared in the cytoplasm, and Alizarin red staining showed a positive reaction for calcified nodules in differentiated BM-MSCs (Fig. 1B-a)

Summary

Introduction

Led to an excessive inflammatory response via TLR4/MyD88 signaling, but the effects of BM-MSCs on TLR4/ MyD88 signaling are unclear. Humans have studied eggs for 2500 years. Eggs are very cheap and suitable for mass production. Unlike other species, such as sheep or hamsters, chickens produce protein in a surprisingly similar way to humans. The vast majority of studies on MSCs mainly concentrate on cells from humans, mice, and rats, but numerous sources for producing these MSCs are not available, and the MSCs cannot be harvested at a low cost. This study could reduce the cost of MSC research and contribute to further studies and the application of MSCs. We attempted to provide a scientific foundation for the use of chicken BM-MSCs and to identify whether BM-MSCs can reduce ALI and extrapulmonary injury. The underlying molecular mechanisms through which BM-MSCs modulated inflammatory parameters and the oxidative stress index in LPS-induced ALI have not yet been fully elucidated

Objectives

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Conclusion