Autophagy: a potential key contributor to the therapeutic action of mesenchymal stem cells

Abstract

Macroautophagy/autophagy occurs at basal levels in all eukaryotic cells and plays an important role in maintaining bio-energetic homeostasis through the control of molecule degradation and organelle turnover. It can be induced by environmental conditions such as starvation, and is deregulated in many diseases including autoimmune diseases, neurodegenerative disorders, and cancer. Interestingly, the modulation of autophagy in mesenchymal stem cells (MSCs) represents a possible mechanism which, affecting MSC properties, may have an impact on their regenerative, therapeutic potential. Furthermore, the ability of MSCs to modulate autophagy of cells in injured tissues/organs has been recently proposed to be involved in the regeneration of damaged tissues and organs. In particular, MSCs can affect autophagy in immune cells involved in injury-induced inflammation reducing their survival, proliferation, and function and favoring the resolution of inflammation. In addition, MSCs can affect autophagy in endogenous adult or progenitor cells, promoting their survival, proliferation and differentiation supporting the restoration of functional tissue. This review provides, for the first time, an overview of the studies which highlight a possible link between the therapeutic properties of MSCs and their ability to modulate autophagy, and it summarizes examples of disorders where these therapeutic properties have been correlated with such modulation. A better elucidation of the mechanism(s) through which MSCs can modulate the autophagy of target cells and how autophagy can affect MSCs therapeutic properties, can provide a wider perspective for the clinical application of MSCs in the treatment of many diseases.

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

“…These findings are inconsistent with current research conclusions obtained from MSCs. In addition, the activation of autophagy is necessary for the proliferation and differentiation of MSCs, and downregulated autophagy can limit the therapeutic actions of MSCs . Therefore, exploring the possible methods to delay MSC senescence through promoting autophagy has important clinical research significance.…”

Growth factors-based beneficial effects of platelet lysate on umbilical cord-derived stem cells and their synergistic use in osteoarthritis treatment

“…And, activation of autophagy contributes to adaptive cell cycle response of MSCs 25 . Moreover, modulation of autophagy may have an impact on the regenerative and therapeutic potential of MSCs 26 . Beclin1 acts as a crucial modifier of autophagy involved in the activation of autophagy and formation of autophagosomes.…”

Dual Role of Autophagy in Regulation of Mesenchymal Stem Cell Senescence

“…As an example, the regulation of autophagy in MSCs exemplifies a conceivable strategy which, influencing MSC characteristics, may hit their regenerative potential, both in terms of differentiation properties and engraftment ability (Ceccariglia et al, 2020). Activation of autophagy promoted osteogenesis in bone marrow-derived MSCs isolated from osteoporotic vertebrae (Wan et al, 2017) and prevented bone loss in elderly mice, suggesting that autophagy has a crucial role in the aging of MSCs; in this setting, autophagy upregulation could partly revert this senescence process exemplifying a likely therapeutic strategy for clinically treating age-related bone loss (Ma et al, 2018).…”