Human Neonatal Thymus Mesenchymal Stem/Stromal Cells and Chronic Right Ventricle Pressure Overload.

Josue Chery,Jeffrey Lee,Shan Huang,Joshua Wong,Sean Johnson,Ming-Sing Si,Lianghui Gong,Shuyun Wang,Zhize Yuan

doi:10.3390/bioengineering6010015

Josue Chery, Jeffrey Lee + Show 7 more

Open Access

https://doi.org/10.3390/bioengineering6010015

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Abstract

Right ventricle (RV) failure secondary to pressure overload is associated with a loss of myocardial capillary density and an increase in oxidative stress. We have previously found that human neonatal thymus mesenchymal stem cells (ntMSCs) promote neovascularization, but the ability of ntMSCs to express the antioxidant extracellular superoxide dismutase (SOD3) is unknown. We hypothesized that ntMSCs express and secrete SOD3 as well as improve survival in the setting of chronic pressure overload. To evaluate this hypothesis, we compared SOD3 expression in ntMSCs to donor-matched bone-derived MSCs and evaluated the effect of ntMSCs in a rat RV pressure overload model induced by pulmonary artery banding (PAB). The primary outcome was survival, and secondary measures were an echocardiographic assessment of RV size and function as well as histological studies of the RV. We found that ntMSCs expressed SOD3 to a greater degree as compared to bone-derived MSCs. In the PAB model, all ntMSC-treated animals survived to the study endpoint whereas control animals had significantly decreased survival. Treatment animals had significantly less RV fibrosis and increased RV capillary density as compared to controls. We conclude that human ntMSCs demonstrate a therapeutic effect in a model of chronic RV pressure overload, which may in part be due to their antioxidative, antifibrotic, and proangiogenic effects. Given their readily available source, human ntMSCs may be a candidate cell therapy for individuals with congenital heart disease and a pressure-overloaded RV.

Highlights

Pressure overload has a profound and deleterious effect on the right ventricle (RV) [1]
We previously found that human neonatal thymus mesenchymal stem cells isolated from discarded tissue obtained from cardiac surgical procedures promote angiogenesis and preserve cardiac function after ischemia [6,7]
We evaluated our hypothesis that neonatal thymus mesenchymal stem cells (ntMSCs) could express and secrete SOD3 and improve RV function and survival in the setting of chronic pressure overload in vivo

Summary

Introduction

Pressure overload has a profound and deleterious effect on the right ventricle (RV) [1]. In response to pressure overload, the left ventricle (LV) undergoes compensatory cardiomyocyte hypertrophy with increased angiogenesis and the antioxidant enzyme extracellular superoxide dismutase (SOD3) [2], thereby diminishing the deleterious effects of the pressure overload [1]. The pathophysiology of RV dysfunction secondary to pressure overload can be mitigated if capillary density is preserved and oxidative stress is reduced. Human bone marrow-derived MSCs exert their antioxidant properties in part via the secretion of the extracellular superoxide dismutase (SOD3) [9]. We evaluated our hypothesis that ntMSCs could express and secrete SOD3 and improve RV function and survival in the setting of chronic pressure overload in vivo

Materials and Methods

Results

Histological Findings