Interleukin-11 regulates the fate of adipose-derived mesenchymal stem cells via STAT3 signalling pathways.

Wenlong Yang,Aijun Sun,Shuning Zhang,Tiantong Ou,Juying Qian,Zhiyong Qi,Junbo Ge,Daile Jia,Yunzeng Zou,Hao Jiang

doi:10.1111/cpr.12771

Abstract

ObjectiveAdipose‐derived mesenchymal stem cells (ADSCs) offer great promise as cell therapy for ischaemic diseases. Due to their poor survival in the ischaemic environment, the therapeutic efficacy of ADSCs is still relatively low. Interleukin‐11 (IL‐11) has been shown to play a key role in promoting cell proliferation and protecting cells from oxidative stress injury. The aim of this study was to determine whether IL‐11 could improve therapeutic efficacy of ADSCs in ischaemic diseases.Methods and ResultsADSCs were prepared from inguinal subcutaneous adipose tissue and exposed to hypoxic environment. The protein expression of IL‐11 was decreased after hypoxic treatment. In addition, ADSCs viability was increased after IL‐11 treatment under hypoxia. Moreover, IL‐11 enhanced ADSCs viability in a dose‐dependent manner under normoxia. Importantly, IL‐11 promoted ADSCs proliferation and migration and protected ADSCs against hydrogen peroxide‐induced cellular death. Notably, IL‐11 enhanced ADSCs proliferation and migration, also promoted cell survival and apoptosis resistance by STAT3 signalling. In vivo, mice were subjected to limb ischaemia and treated with IL‐11 overexpression ADSCs and control ADSCs. IL‐11 overexpression ADSCs improved perfusion recovery in the ischaemic muscles.ConclusionsWe provide the evidence that IL‐11 promoted ADSCs proliferation, stimulated ADSCs migration and attenuated ADSCs apoptosis by activation of STAT3 signalling. These results suggest that IL‐11 facilitated ADSCs engraftment in ischaemic tissue, thereby enhanced ADSCs therapeutic efficacy.

Highlights

Mesenchymal stem cells (MSCs) are multipotent stromal cells from many tissue sources, including the bone marrow, adipose tissue, umbilical cord and other adult tissues.[1]
To determine the molecular mechanisms underlying the effects of IL-11 upon adipose-derived mesenchymal stem cells (ADSCs), we examined the expression of P-STAT3, P-ERK1/2 and P-mTOR in ADSCs with IL-11 treatment
We demonstrated that IL-11 promoted ADSCs proliferation, migration and protected ADSCs from hydrogen peroxide-induced cell apoptosis via STAT3 signalling pathway in vitro

Summary

| INTRODUCTION

Mesenchymal stem cells (MSCs) are multipotent stromal cells from many tissue sources, including the bone marrow, adipose tissue, umbilical cord and other adult tissues.[1]. Multiple studies utilizing MSCs have been conducted, being considered a promising treatment for ischaemic tissue injuries, such as hindlimb ischaemia and myocardial infarction.[4-6]. Multiple studies have been performed to use adipose-derived mesenchymal stem cells (ADSCs) for the revascularization and tissue. Studies have shown that IL-11 prevents skeletal myoblasts apoptosis and endothelial cell injury under oxidant stress via STAT3 signalling pathway.[23,24]. We performed a pre-clinical study to explore the role of IL-11 as a potential pharmacological agent for improving the efficacy of stem cell therapy using a hindlimb ischaemia mouse model. We examined whether IL-11 treatment improves ADSCs therapeutic efficiency in hindlimb ischaemia tissues and explored the underlying mechanisms of IL-11 in regulating the function of ADSCs under oxidative stress

| MATERIALS AND METHODS

| DISCUSSION