Stem cell senescence. Effects of REAC technology on telomerase-independent and telomerase-dependent pathways

Abstract

Decline in the gene expression of senescence repressor Bmi1, and telomerase, together with telomere shortening, underlay senescence of stem cells cultured for multiple passages. Here, we investigated whether the impairment of senescence preventing mechanisms can be efficiently counteracted by exposure of human adipose-derived stem cells to radio electric asymmetrically conveyed fields by an innovative technology, named Radio Electric Asymmetric Conveyer (REAC). Due to REAC exposure, the number of stem cells positively stained for senescence associated β-galactosidase was significantly reduced along multiple culturing passages. After a 90-day culture, REAC-treated cells exhibited significantly higher transcription of Bmi1 and enhanced expression of other stem cell pluripotency genes and related proteins, compared to unexposed cells. Transcription of the catalytic telomerase subunit (TERT) was also increased in REAC-treated cells at all passages. Moreover, while telomere shortening occurred at early passages in both REAC-treated and untreated cells, a significant rescue of telomere length could be observed at late passages only in REAC-exposed cells. Thus, REAC-asymmetrically conveyed radio electric fields acted on a gene and protein expression program of both telomerase-independent and telomerase-dependent patterning to optimize stem cell ability to cope with senescence progression.

Seeing Cell Biology with the Eyes of Physics

“…Intriguingly, the exposure to properly conveyed radio electric fields was able to reverse the senescence of human adult stem cells in vitro [39]. REAC treatment significantly decreased the number of human adipose-derived mesenchymal stem cells (hADSCs) positively stained for senescenceassociated β-galactosidase along multiple culturing passages [39].…”

“…REAC treatment significantly decreased the number of human adipose-derived mesenchymal stem cells (hADSCs) positively stained for senescenceassociated β-galactosidase along multiple culturing passages [39]. After 30 passages in culture, the REAC treatment was able to re-express the TERT gene, encoding the catalytic core of telomerase, increasing the telomere length, with full recovery of the multilineage potential of hADSCs [39].…”

“…REAC treatment significantly decreased the number of human adipose-derived mesenchymal stem cells (hADSCs) positively stained for senescenceassociated β-galactosidase along multiple culturing passages [39]. After 30 passages in culture, the REAC treatment was able to re-express the TERT gene, encoding the catalytic core of telomerase, increasing the telomere length, with full recovery of the multilineage potential of hADSCs [39]. The antiaging action of REAC also encompassed the induction of a telomerase-independent pathway, upregulating the transcription of Bmi-1, an orchestrator of the expression of stemness related genes and proteins, which also resulted to be induced by the REAC treatment of senescent stem cells [39].…”

Cancer Stem Cells: Foe or Reprogrammable Cells for Efficient Cancer Therapy?

“…This effect resulted from and was associated with (i) the activation of a telomerase dependent pathway, linked to the re-expression of TERT, the gene coding for the catalytic core of telomerase with subsequent increase in telomere length [77], (ii) the induction of a telomerase independent pathway associated with the activation of Bmi-1 and the transient increase in the expression of pluripotency genes, such as Nanog, Sox2 and Oct4 [77], and (iii) the resumption of multilineage differentiation potential, as shown by recovery of high throughput of differentiation along vasculogenic, osteogenic, and adipogenic fates [78].…”

Biophysical signalling from and to the (stem) cells: a novel path to regenerative medicine

“…Intriguingly, exposure of hADSCs to REAC‐conveyed radioelectric fields was able to reverse their senescence in vitro . REAC treatment significantly decreased the number of hADSCs positively stained for senescence‐associated β‐galactosidase along multiple culturing passages .…”