Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplificat...

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Bibliographic Details
Published in:Experimental cell research 2021-09, Vol.406 (1), p.112740, Article 112740
Main Authors: Delben, Priscilla Barros, Zomer, Helena Debiazi, Acordi da Silva, Camila, Gomes, Rogério Schutzler, Melo, Fernanda Rosene, Dillenburg-Pilla, Patricia, Trentin, Andrea Gonçalves
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ABDOMEN
ANIMAL TISSUES
Cell therapy
ERRORS
Fat depots
FATS
GALACTOSIDASE
GENETICS
H2AX
IN VITRO
Mesenchymal stem cells
MSC
MUTATIONS
Neural crest
PHENOTYPE
STEM CELLS
THERAPY
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Summary:Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, and these had higher proliferative potential, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-β-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γ-H2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2021.112740