Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence.

Gee-Hye Kim,Miyeon Kim,Yun Kyung Bae,Hye Jin Jin,Soo Jin Choi,Ji Hye Kwon,Wonil Oh,Soyoun Um,Ryan Moseley

doi:10.1155/2021/5582792

Abstract

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro (p < 0.01), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

Highlights

Autophagy is a natural intracellular degradation mechanism that maintains cellular homeostasis by delivery to the lysosome [1]
This study reported that CD47 is a key regulator of autophagy and senescence to maintain and orchestrate the aging of mesenchymal stem cells (MSCs)
The result was consistent with downregulated protein levels of autophagyrelated markers in UCB-MSCs. These results suggest that the senescent UCB-MSCs have lower autophagy, which can be correlated by the lower CD47 expression

Summary

Introduction

Autophagy is a natural intracellular degradation mechanism that maintains cellular homeostasis by delivery to the lysosome [1]. The coordinated response to starvation and metabolic stress triggers autophagy to function in the recruitment and degradation of cytosolic proteins and organelles to remove and recycle any malfunctioning or unnecessary components [2]. It is clear that autophagy plays a role in controlling inflammation and is closely implicated in human disease [1, 3, 4]. An intracellular self-degradation system, is responsible for the removal of damaged organelles or malformed proteins, in order to regenerate newer and healthier cells. Understanding autophagy function is important to clarify the cause of diseases. Autophagy has a bifunctional role in cell survival and death, presumably by clearing potential toxic protein aggregates. Blocking autophagy suppresses cytochrome c release from mitochondria and caspase activation and induces cell viability [9]

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Conclusion