Abstract
The capacity of the polyamine copper chelator tetraethylenepentamine (TEPA) to induce a marked expansion of human cord blood-derived CD34+ cells was previously demonstrated (Peled T. et al 2002, Br. J. of Haematology 116:655–661). To examine the effect of TEPA also on the ex-vivo expansion of bone marrow (BM)-derived stem cells, we have isolated AC133+ cells from fresh human BM at purities greater than 90% as measured by FACS. Cell cultures (1×104/ml) were expanded in Teflon bags, in the presence of IL-6, TPO, Flt3 ligand and SCF with or without TEPA (5 uM) for 3 weeks and further incubated with cytokines only. Cell types were analyzed by FACS. Total mononuclear cell (TMC) expansion was 1216 ± 176-fold after 5 weeks in TEPA-treated cultures, representing a 2.5- fold higher expansion level as compared to a cytokines-treated control population. 3-weeks old cultures displayed similar amounts of CD34+ and AC133+ cells, irrelevant of treatment. However, following 5 weeks of ex-vivo expansion, TEPA-treated cultures exhibited a significant increase (16.5-fold) in AC133+ cells and in CD34+ cells (105-fold) expansion, as compared to a cytokines-treated control population. In addition, CFU following 5 weeks ex-vivo expansion was 21.4 higher in TEPA-treated cultures, as compared to a cytokines-treated control population. Significantly, the number of AC133+/CD38- cells following 3 weeks ex-vivo expansion was 26-fold, as compared to a cytokines-treated control population. The data presented here strengthen the usefulness of copper chelators to induce proliferation of early progenitors that influence the long term survival and proliferation of early subset populations which are especially reduced in bone marrow as compared to cord blood. The potential of TEPA for increased ex-vivo expansion of long term capacity stem cells derived from sources other than cord blood can provide stem cell-based therapies platform for the autologous treatment of vascular, cardiovascular, diabetes, hepatic, neurodegenerative, skeletal, and other clinical indications.
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