Conclusions
Pharmacological inhibition of GSK-3β provided a novel approach to improve early engraftment of ex vivo-expanded haematopoietic progenitor cells.
Methods
Immunocompromised mice were employed in transplantation studies to determine stem-cell engraftment. Flow cytometry was used to phenotype the engrafted human cells. Retroviral gene transfer was used to examine the role of Myc gene up-regulated by GSK-3β inhibition, in ex vivo-expanded stem cells.
Results
Treatment with GSK-3β inhibitor, 6-bromoindirubin 3'-oxime (BIO) improved early human cell engraftment in the mice and elevated the numbers of myeloid progenitor cells in cytokine-stimulated culture. BIO up-regulated β-catenin and c-myc in ex vivo-expanded stem cells. Ectopic expression of Myc acted to increase clonogenic potential and to delay differentiation of haematopoietic progenitor cells, suggesting the potential mechanism to improve regenerative potential of ex vivo-expanded grafts. Conclusions: Pharmacological inhibition of GSK-3β provided a novel approach to improve early engraftment of ex vivo-expanded haematopoietic progenitor cells.