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TISSUE-SPECIFIC STEM CELLS

Insulin-Like Growth Factor-Binding Protein 2 Secreted by a Tumorigenic Cell Line Supports Ex Vivo Expansion of Mouse Hematopoietic Stem Cells

Departments of ^aPhysiology and
^bDevelopmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA;
^dWhitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA;
^cDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

Key Words. Ex vivo expansion • Hematopoietic stem cells • Cell culture • Cytokines • Flow cytometry • Growth factors • Hematopoietic stem cell transplantation

Correspondence: Cheng Cheng Zhang, Ph.D., Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA. Telephone: 214-645-6320; Fax: 214-648-1960; e-mail: Alec.Zhang{at}UTSouthwestern.edu

Received January 20, 2008; accepted for publication March 19, 2008.
First published online in STEM CELLS EXPRESS   March 27, 2008.

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.