Dual Role of Autophagy in Regulation of Mesenchymal Stem Cell Senescence.

Emanuela Vitale,Claudia Giachino,Raffaella Rastaldo

doi:10.3389/fcell.2020.00276

Emanuela Vitale, Claudia Giachino + Show 1 more

Open Access

https://doi.org/10.3389/fcell.2020.00276

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Abstract

During their development and overall life, mesenchymal stem cells (MSCs) encounter a plethora of internal and external stress signals and therefore, they need to put in action homeostatic changes in order to face these stresses. To this aim, similar to other mammalian cells, MSCs are endowed with two crucial biological responses, autophagy and senescence. Sharing of a number of stimuli like shrinkage of telomeres, oncogenic and oxidative stress, and DNA damage, suggest an intriguingly close relationship between autophagy and senescence. Autophagy is at first reported to suppress MSC senescence by clearing injured cytoplasmic organelles and impaired macromolecules, yet recent investigations also showed that autophagy can promote MSC senescence by inducing the production of senescence-associated secretory proteins (SASP). These apparently contrary contributions of autophagy may mirror an intricate image of autophagic regulation on MSC senescence. We here tackle the pro-senescence and anti-senescence roles of autophagy in MSCs while concentrating on some possible mechanistic explanations of such an intricate liaison. Clarifying the autophagy/senescence relationship in MSCs will help the development of more effective and safer therapeutic strategies.

Highlights

Mesenchymal stem cells (MSCs) are the most widely utilized adult stem cells in clinical trials (Trounson and McDonald, 2015)
Thorough investigation has substantiated the capability of MSCs to differentiate into cells of the mesenchymal lineage including osteoblasts, chondrocytes and adipocytes, and to secrete several trophic components able to exert their effect at cellular level like apoptosis and differentiation, at systemic level like immune response modulation and at tissue level like angiogenesis and fibrosis; further, MSCs sustain cardiac, muscle, and neural tissue regeneration
Similar to human fibroblasts (Rodier et al, 2009), human MSC senescence program was sustained by persistent DNA damage repair activation, evidenced by the detection of characteristic enlarged nuclear foci, containing γH2AX and 53BP1 proteins (Cmielova et al, 2012; Seifrtova et al, 2013; Minieri et al, 2015; Turinetto and Giachino, 2015)

Summary

Dual Role of Autophagy in Regulation of Mesenchymal Stem Cell Senescence

Stem Cell Research, a section of the journal Frontiers in Cell and Developmental During their development and overall life, mesenchymal stem cells (MSCs) encounter a plethora of internal and external stress signals and they need to put in action homeostatic changes in order to face these stresses. To this aim, similar to other mammalian cells, MSCs are endowed with two crucial biological responses, autophagy and senescence. Autophagy is at first reported to suppress MSC senescence by clearing injured cytoplasmic organelles and impaired macromolecules, yet recent investigations showed that autophagy can promote MSC senescence by inducing the production of senescence-associated secretory proteins (SASP) These apparently contrary contributions of autophagy may mirror an intricate image of autophagic regulation on MSC senescence.

INTRODUCTION

CLINICAL IMPLICATIONS