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.
Jiang
Junfen
J
Laboratory of Regeneromics, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Zhao
Mei
M
Zhang
Aiying
A
Yu
Mingfeng
M
Lin
Xiaojuan
X
Wu
Mingyuan
M
Wang
Xiaonong
X
Lu
Huili
H
Zhu
Shunying
S
Yu
Yan
Y
Mao
Zhenmin
Z
Han
Wei
W
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology
C483321:6-bromoindirubin-3'-oxime; D018952:Antigens, CD34; D007211:Indoles; D010091:Oximes; D019089:Stem Cell Factor; D038362:Glycogen Synthase Kinase 3