Characterization of a GSK-3 inhibitor in culture of human cord blood primitive hematopoietic cells.

Wnt signaling pathway plays important roles in the biology of stem cells in maintaining their self-renewal property. Glycogen synthase kinase-3 (GSK-3) inhibitors, the Wnt signaling agonists, maintain the pluripotency of embryonic stem cells. We report here that a synthetic GSK-3 inhibitor, 6-bromoindirubin-3'-oxime (BIO), showed opposite effects on the expansion of human primitive hematopoietic cells isolated from umbilical cord blood (UCB). In combination with human c-kit ligand (KL), BIO at low concentration (0.2 μM) enhanced the expansion of UCB CD34+ cells, which was BIO structure and exposure time dependent; however, at high concentration (2 μM) it inhibited the expansion of the cells. Furthermore, hematopoietic stem cells (HSCs) were exhausted when the UCB CD34+ cells were exposed to 0.2 μM BIO and KL longer than 2 days. In conclusion, the use of BIO in expansion of UCB HSCs remains a significant challenge.