Biosafety evidence for human dedifferentiated adipocytes

Antonella Poloni, Giulia Maurizi, Domenico Mattiucci, Elena Busilacchi, Stefania Mancini, Giancarlo Discepoli, Augusto Amici, Massimo Falconi, Saverio Cinti, Pietro Leoni

Research output: Contribution to journalArticle

Abstract

Mature adipocytes have shown dynamic plasticity to be converted into fibroblast-like and lipid-free cells. After the dedifferentiation process, these cells re-entered the cell cycle and acquired a high proliferation potential, becoming a valid source of stem cells. However, many aspects of the cellular biosafety about dedifferentiated fat cells remained unclear. This study aimed to elucidate their potential susceptibility to malignant transformation and to ascertain the safety of these cells for clinical use. To evaluate the genomic stability of dedifferentiated adipocytes, telomere length, hTERT gene transcription, the capacity of these cells to grow in an anchorage-independent manner and the presence of DNA damage by single cell gel electrophoresis assay were studied. Spontaneous chromosomal alterations were excluded by cytogenetic analysis and the expression level of c-myc and p53, tumor associated genes, were assessed, evaluating also p53 loss of function mutations. Despite the high proliferation capacity of dedifferentiated adipocytes, these cells showed stable telomere length compared with mature adipocytes, no hTERT transcriptions and consequently no telomerase activity, suggesting that both transformation and senescence were avoided. A constant expression level of c-myc and p53, the inability of dedifferentiated adipocytes to grow in an anchorage-independent manner, the absence of DNA damage suggested the safety of these cells. Moreover, a normal karyotype was preserved throughout the dedifferentiation process. Data in vivo showed that dedifferentiated adipocytes analyzed for tumorigenicity did not develop tumors. In conclusion, our data indicated that dedifferentiated adipocytes could be a relatively easily accessible resource for cell therapy and regenerative medicine.

Original languageEnglish
Pages (from-to)1525-1533
Number of pages9
JournalJournal of Cellular Physiology
Volume230
Issue number7
DOIs
Publication statusPublished - Jul 1 2015

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Medicine(all)

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  • Cite this

    Poloni, A., Maurizi, G., Mattiucci, D., Busilacchi, E., Mancini, S., Discepoli, G., Amici, A., Falconi, M., Cinti, S., & Leoni, P. (2015). Biosafety evidence for human dedifferentiated adipocytes. Journal of Cellular Physiology, 230(7), 1525-1533. https://doi.org/10.1002/jcp.24898