Abstract

The decline of cell function caused by ageing directly impacts the therapeutic effects of autologous stem cell transplantation for heart repair. The aim of this study was to investigate whether overexpression of neuron‐derived neurotrophic factor (NDNF) can rejuvenate the adipose‐derived stem cells in the elderly and such rejuvenated stem cells can be used for cardiac repair. Human adipose‐derived stem cells (hADSCs) were obtained from donors age ranged from 17 to 92 years old. The effects of age on the biological characteristics of hADSCs and the expression of ageing‐related genes were investigated. The effects of transplantation of NDNF over‐expression stem cells on heart repair after myocardial infarction (MI) in adult mice were investigated. The proliferation, migration, adipogenic and osteogenic differentiation of hADSCs inversely correlated with age. The mRNA and protein levels of NDNF were significantly decreased in old (>60 years old) compared to young hADSCs (<40 years old). Overexpression of NDNF in old hADSCs significantly improved their proliferation and migration capacity in vitro. Transplantation of NDNF‐overexpressing old hADSCs preserved cardiac function through promoting angiogenesis on MI mice. NDNF rejuvenated the cellular function of aged hADSCs. Implantation of NDNF‐rejuvenated hADSCs improved angiogenesis and cardiac function in infarcted mouse hearts.

Highlights

  • Global coronary heart disease, especially acute myocardial infarction (MI), is associated with high morbidity and mortality, and the age of first MI is decreasing.[1]

  • We focus on adipose‐derived stem cells (ADSCs) transplantation for the treatment of acute MI and investigated its efficacy for cardiac repair and regeneration

  • The results showed that baseline function before MI was similar among the four groups with respect to FS (Figure 5B), EF (Figure 5C), Left Ventricular Internal Dimension‐diastole (LVIDd, Figure 5D) and Left Ventricular Internal Dimension in systole (LVIDs, Figure 5E)

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Summary

Introduction

Especially acute myocardial infarction (MI), is associated with high morbidity and mortality, and the age of first MI is decreasing.[1]. Progression to congestive heart failure remains a significant global health crisis, especially in aged populations. Since current therapies focus on the restoration of blood flow to the defect area, the damaged cardiomyocytes are unable to regenerate and are replaced by fibroblasts and collagen matrix (fibrotic scar tissue). This scar tissue becomes thin and inelastic, leading to ventricular chamber dilation and progression to congestive heart failure.[4]

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