title: Biosafety evidence for human dedifferentiated adipocytes.
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.
authors: Clinica di Ematologia, Dipartimento Scienze Mediche e Chirurgiche, Università Politecnica delle Marche, Ancona, Italy.
authors: Antonella
authors: A
authors: Poloni
authors: Giulia
authors: G
authors: Maurizi
authors: Domenico
authors: D
authors: Mattiucci
authors: Elena
authors: E
authors: Busilacchi
authors: Stefania
authors: S
authors: Mancini
authors: Giancarlo
authors: G
authors: Discepoli
authors: Augusto
authors: A
authors: Amici
authors: Massimo
authors: M
authors: Falconi
authors: Saverio
authors: S
authors: Cinti
authors: Pietro
authors: P
authors: Leoni
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D063646:Carcinogenesis; D054337:Cell Dedifferentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D020552:Comet Assay; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D059785:Karyotype; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009374:Neoplasms, Experimental; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; C509186:TERT protein, human; D019098:Telomerase