Human Bone Marrow Mesenchymal Stem cells (hMSC) are a promising candidate for cytotherapy.
However, the therapeutic potential is limited since the therapy requires ex-vivo cell culturing in which
deterioration in cellular viability and aging is observed with time.
Telomerase ribonucleoprotein complex re-elongates telomeres and therefore promotes genomic integrity,
proliferation and lifespan. Recently we showed that increasing telomerase reverse transcriptase (TERT)
expression by novel compound confers resistance from apoptosis induced by oxidative stress. Here we
investigated the possibility that a controlled induction of human TERT (hTERT) levels by chemical compounds
(AGS-499 and AGS-500) might improve the functionality of hMSC derived from healthy and neurodegenerative
diseased individuals. We demonstrate that AGS treatments of hMSC increased telomerase activity and hTERT
levels in a time and dose dependent manner. Prolonged treatments with the compounds increased the
average telomeres length, without altering population doublings (PD) or inducing chromosomal aberrations.
AGS treatments of hMSC protected the cells from apoptosis and DNA damages induced by H2O2, and from the
toxicity induced by long term exposure to DMSO. These AGS effects were shown to be mediated by
telomerase since they were not observed when TERT was depleted from hMSC or in mouse embryonic stem
cells derived from TERT knockout mice. Furthermore, AGS compounds did not alter the functionality of hMSC
as examined by their ability to differentiate into various lineages in the presence of the compounds. These
results suggest that pharmaceutical increase of telomerase may confer a beneficial therapeutic advantage in
regenerative medicine when hMSC therapy is applied.