TY - JOUR
T1 - Insulin-like growth factor-binding protein 2 secreted by a tumorigenic cell line supports ex vivo expansion of mouse hematopoietic stem cells
AU - Huynh, HoangDinh
AU - Iizuka, Satoru
AU - Kaba, Megan
AU - Kirak, Oktay
AU - Zheng, Junke
AU - Lodish, Harvey F.
AU - Zhang, Chengcheng
PY - 2008/6
Y1 - 2008/6
N2 - Successful hematopoietic stem cell (HSC) transplantation is often limited by the numbers of HSCs, and robust methods to expand HSCs ex vivo are needed. We previously showed that angiopoietin-like proteins (Angptls), a group of growth factors isolated from a fetal liver HSC-supportive cell population, improved ex vivo expansion of HSCs. Here, we demonstrate that insulin-like growth factor-binding protein 2 (IGFBP2), secreted by a tumorigenic cell line, also enhanced ex vivo expansion of mouse HSCs. On the basis of these findings, we established a completely defined, serum-free culture system for mouse HSCs, containing SCF, thrombopoietin, fibroblast growth factor 1, Angptl3, and IGFBP2. As measured by competitive repopulation analyses, there was a 48-fold increase in numbers of long-term repopulating mouse HSCs after 21 days of culture. This is the first demonstration that IGFBP2 stimulates expansion or proliferation of murine stem cells. Our finding also suggests that certain cancer cells synthesize proteins that can stimulate HSC expansion.
AB - Successful hematopoietic stem cell (HSC) transplantation is often limited by the numbers of HSCs, and robust methods to expand HSCs ex vivo are needed. We previously showed that angiopoietin-like proteins (Angptls), a group of growth factors isolated from a fetal liver HSC-supportive cell population, improved ex vivo expansion of HSCs. Here, we demonstrate that insulin-like growth factor-binding protein 2 (IGFBP2), secreted by a tumorigenic cell line, also enhanced ex vivo expansion of mouse HSCs. On the basis of these findings, we established a completely defined, serum-free culture system for mouse HSCs, containing SCF, thrombopoietin, fibroblast growth factor 1, Angptl3, and IGFBP2. As measured by competitive repopulation analyses, there was a 48-fold increase in numbers of long-term repopulating mouse HSCs after 21 days of culture. This is the first demonstration that IGFBP2 stimulates expansion or proliferation of murine stem cells. Our finding also suggests that certain cancer cells synthesize proteins that can stimulate HSC expansion.
KW - Cell culture
KW - Cytokines
KW - Ex vivo expansion
KW - Flow cytometry
KW - Growth factors
KW - Hematopoietic stem cell transplantation
KW - Hematopoietic stem cells
UR - http://www.scopus.com/inward/record.url?scp=48649090483&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48649090483&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2008-0064
DO - 10.1634/stemcells.2008-0064
M3 - Article
C2 - 18369099
AN - SCOPUS:48649090483
SN - 1066-5099
VL - 26
SP - 1628
EP - 1635
JO - STEM CELLS
JF - STEM CELLS
IS - 6
ER -