Ions modulate self-renewal and differentiation of cultured hematopoietic (blood) progenitor cells (HPC). Copper deficiency delays differentiation and prolongs proliferation while increasing the cellular copper level, accelerating differentiation and substantially reducing proliferation potential. (Exp Hematol. 2005; 33:1092). Of note, copper deficiency in patients was shown to mimic refractory anemia manifested by excess of immature cells and to reduce the proportion of differentiated cells in the bone marrow. Oral copper replacement completely normalized the bone marrow findings (Leuk Res. 2008; 32(3):495). As such, this mechanism is used to modify the balance between self renewal and differentiation in vitro and in vivo (inside a living body).
The lead molecule of the copper-based technology is the high affinity copper chelator Tetraethylpentamine (TEPA). TEPA reduces the intracellular copper level, delays differentiation, and enables robust expansion of a populations of HPC during the first few weeks in culture. Pre-clinical in vivo data show that the resulting cell population contains increased proportions and absolute numbers of HPC displaying increased self-renewal potential, and shows high levels of engraftment as well as multi-lineage differentiation potential. (Exp Hematol. 2004 Jun;32(6):547-55.)
Gamida Cell applied TEPA to create StemEx®, its flagship product to treat blood cancers. | 
