Insulin-like growth factor-binding protein 2 secreted by a tumorigenic cell line supports ex vivo expansion of mouse hematopoietic stem cells.
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. Disclosure of potential conflicts of interest is found at the end of this article.
Huynh
Hoangdinh
H
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Iizuka
Satoru
S
Kaba
Megan
M
Kirak
Oktay
O
Zheng
Junke
J
Lodish
Harvey F
HF
Zhang
Cheng Cheng
CC
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015626:Tissue Expansion / Q000379:methods*; D014162:Transfection
D017077:Culture Media, Conditioned; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1