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Review
. 2024 Aug 1;25(15):8390.
doi: 10.3390/ijms25158390.

Senescence in Adipose-Derived Stem Cells: Biological Mechanisms and Therapeutic Challenges

Riccardo Foti  1 , Gabriele Storti  1 , Marco Palmesano  1 , Maria Giovanna Scioli  2 , Elena Fiorelli  2 , Sonia Terriaca  2 , Giulio Cervelli  3 , Bong Sung Kim  4 , Augusto Orlandi  2 , Valerio Cervelli  1
Affiliations
Review

Senescence in Adipose-Derived Stem Cells: Biological Mechanisms and Therapeutic Challenges

Riccardo Foti et al. Int J Mol Sci. .

Abstract

Adipose tissue-derived stem cells (ADSCs) represent a subset of the mesenchymal stem cells in every adipose compartment throughout the body. ADSCs can differentiate into various cell types, including chondrocytes, osteocytes, myocytes, and adipocytes. Moreover, they exhibit a notable potential to differentiate in vitro into cells from other germinal lineages, including endothelial cells and neurons. ADSCs have a wide range of clinical applications, from breast surgery to chronic wounds. Furthermore, they are a promising cell population for future tissue-engineering uses. Accumulating evidence indicates a decreased proliferation and differentiation potential of ADSCs with an increasing age, increasing body mass index, diabetes mellitus, metabolic syndrome, or exposure to radiotherapy. Therefore, the recent literature thoroughly investigates this cell population's senescence mechanisms and how they can hinder its possible therapeutic applications. This review will discuss the biological mechanisms and the physio-pathological causes behind ADSC senescence and how they can impact cellular functionality. Moreover, we will examine the possible strategies to invert these processes, re-establishing the full regenerative potential of this progenitor population.

Keywords: adipose-derived stem cells; ageing; diabetes; mesenchymal stem cells; senescence; senolytic drugs; stem cell therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Pathways modulated in senescent ADSCs. Senescent ADSCs are identified by elevated levels of intracellular markers such as p16, p21, senescence-associated β-galactosidase (SA-β-gal), and 5-hydroxymethylcytosine (5hmc) while experiencing a decrease in PKC-δ levels. Additionally, these cells exhibit a senescence-associated secretory phenotype (SASP), which is characterized by an increased release of inflammatory cytokines (IL-1, IL-6, IL-8, MCP-1, and RANTES) and anti-angiogenetic mediators (IL-4, IFN-a2, IP10, IL-1b, PF4, DPPIV, and Activin A), further defining the altered functional state of senescent ADSCs.
Figure 2
Figure 2
Factors promoting ADSCs’ senescence. Obesity, diabetes, aging, metabolic syndrome, oxidative stress, environmental factors, and chronic inflammation are considered key factors that promote increased senescence in adipose-derived stem cells (ADSCs). These conditions contribute to accelerated cellular aging and dysfunction, potentially impacting the regenerative capabilities of ADSCs.
See this image and copyright information in PMC

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