Decreased Insulin Sensitivity in Telomerase-Immortalized Mesenchymal Stem Cells Affects Efficacy and Outcome of Adipogenic Differentiation in vitro

Modern biomedical science still experiences a significant need for easy and reliable sources of human cells. They are used to investigate pathological processes underlying disease, conduct pharmacological studies, and eventually applied as a therapeutic product in regenerative medicine. For decades,...

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Published in:Frontiers in cell and developmental biology 2021-08, Vol.9, p.662078-662078
Main Authors: Kulebyakin, Konstantin, Tyurin-Kuzmin, Pyotr, Efimenko, Anastasia, Voloshin, Nikita, Kartoshkin, Anton, Karagyaur, Maxim, Grigorieva, Olga, Novoseletskaya, Ekaterina, Sysoeva, Veronika, Makarevich, Pavel, Tkachuk, Vsevolod
Format: Article
Language:English
Subjects:
adipogenic differentiation
Cell and Developmental Biology
chondrogenic differentiation
insulin signaling
mesenchymal stem/stromal cells
osteogenic differentiation
protein kinase A signaling
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Summary:Modern biomedical science still experiences a significant need for easy and reliable sources of human cells. They are used to investigate pathological processes underlying disease, conduct pharmacological studies, and eventually applied as a therapeutic product in regenerative medicine. For decades, the pool of adult mesenchymal stem/stromal cells (MSCs) remains a promising source of stem and progenitor cells. Their isolation is more feasible than most other stem cells from human donors, yet they have a fair share of drawbacks. They include significant variability between donors, loss of potency, and transformation during long-term culture, which may impact the efficacy and reproducibility of research. One possible solution is a derivation of immortalized MSCs lines which receive a broader use in many medical and biological studies. In the present work, we demonstrated that in the most widely spread commercially available hTERT-immortalized MSCs cell line ASC52telo, sensitivity to hormonal stimuli was reduced, affecting their differentiation efficacy. Furthermore, we found that immortalized MSCs have impaired insulin-dependent and cAMP-dependent signaling, which impairs their adipogenic, but not osteogenic or chondrogenic, potential under experimental conditions. Our findings indicate that hTERT-immortalized MSCs may present a suboptimal choice for studies involving modeling or investigation of hormonal sensitivity.
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2021.662078