The therapeutic impact of human neonatal BMSC in a right ventricular pressure overload model in mice

Rong Liufu,Zhongqun Zhu,Fang Zhu,Guocheng Shi,Wei Liu,Xiaomin He,Huiwen Chen,Chen Wen,Jingjing Lv

doi:10.1186/s13287-020-01593-y

Abstract

ObjectiveTo determine the impact of donor age on the therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) in treating adverse remodeling as the result of right ventricle (RV) pressure overload.MethodsBMSCs were isolated from neonatal (< 1 month), infant (1 month to 1 year), and young children (1 year to 5 years) and were compared in their migration potential, surface marker expression, VEGF secretion, and matrix metalloprotein (MMP) 9 expression. Four-week-old male C57 mice underwent pulmonary artery banding and randomized to treatment and untreated control groups. During the surgery, BMSCs were administered to the mice by intramyocardial injection into the RV free wall. Four weeks later, RV function and tissue were analyzed by echocardiography, histology, and quantitative real-time polymerase chain reaction.ResultsHuman neonatal BMSCs demonstrated the greatest migration capacity and secretion of vascular endothelial growth factor but no difference in expression of surface markers. Neonate BMSCs administration resulted in increasing expression of VEGF, a significant reduction in RV wall thickness, and internal diameter in mice after PA banding. These beneficial effects were probably associated with paracrine secretion as no cardiomyocyte transdifferentiation was observed.ConclusionsHuman BMSCs from different age groups have different characteristics, and the youngest BMSCs may favorably impact the application of stem cell-based therapy to alleviate adverse RV remodeling induced by pressure overload.

Highlights

Since their identification by Friedenstein et al [1], bone marrow-derived mesenchymal stem cells (BMSCs) have been known for their high proliferative potential, ability to differentiate into other cell lineages [2], support of hematopoietic cells, and promotion of the secretion of various cytokines including vascular endothelial growth factor (VEGF) [3]
BMSCs from neonate donors increased the expression of VEGF We further examined the expression of cytokines including VEGF, Hepatocyte growth factor (HGF), and Heat shock protein 70 (Hsp70) in BMSCs from different age groups
pulmonary artery banding (PAB)-induced hypertrophy was prevented by neonatal BMSC transplantation in the right ventricle (RV) wall, which was revealed by a reduction in RV thickness and right ventricular internal diameter (RVID)

Summary

Introduction

Since their identification by Friedenstein et al [1], bone marrow-derived mesenchymal stem cells (BMSCs) have been known for their high proliferative potential, ability to differentiate into other cell lineages [2], support of hematopoietic cells, and promotion of the secretion of various cytokines including vascular endothelial growth factor (VEGF) [3] These impressive abilities have encouraged extensive research on stem cell-based therapies. It was reported that human BMSCs probably preserve cardiac function by inducing participation of VEGF in the anti-hypertrophic pathway in vivo [10] This particular paracrine secretion of BMSC tended to have an age-associated decline, limiting the potential of cell-based therapy to some extent. To date, evidence of age-associated effects on BMSC-based therapy remains insufficient

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