Effect of insulin-like growth factor 1 on PHA-stimulated cord blood mononuclear cell telomerase activity.

Abstract

Telomerase may contribute to the capacity for cell replication by compensating for the loss of telomere length. Exploring the use of biological modifiers in increasing cellular replicative potential through telomerase activity may be useful for in vitro expansion of haemopoietic stem cells for transplantation or lymphoid cells for adoptive immunotherapy. In this study we showed for the first time that insulin-like growth factor 1 (IGF-1) modulated telomerase activity in human cord blood mononuclear cells (MNC) and some of the known functional determinants of telomerase activity. We found that cord blood MNC expressed constitutively a low level of telomerase activity and human telomerase reverse transcriptase (hTRT) mRNA, and a high level of human telomerase RNA component (hTR) and telomerase-associated protein-1 (TP1) mRNA. Interestingly, IGF-I alone did not increase the telomerase activity of cord blood MNC but could enhance the PHA-induced increase in telomerase activity. These alterations in telomerase activity were not completely in phase with those of proliferation response. On the other hand, IGF-I did not alter hTRT mRNA expression but enhanced the PHA-induced increase in hTRT whereas TP1 mRNA expression was stimulated by either IGF-I or PHA but showed no additive increase when stimulated by both IGF-1 and PHA. Neither IGF-1 nor PHA altered hTR expression. Finally, the temporal dynamics of hTRT mRNA expression and telomerase activity in cord blood MNC over 5 d in culture were not totally concordant. suggesting that key factors other than hTRT were involved in regulating telomerase activity in cord blood MNC. The modulatory effect of IGF-1 on telomerase activity supports its potential role in increasing replicative potential of cord blood lymphoid cells or haemopoietic stem cells.