title: Recombinant IL-7/HGFβ efficiently induces transplantable murine hematopoietic stem cells.
abstract: Difficulty obtaining sufficient hematopoietic stem cells (HSCs) directly from the donor has limited the clinical use of HSC transplantation. Numerous attempts to stimulate the ex vivo growth of purified HSCs with cytokines and growth factors generally have induced only modest increases in HSC numbers while decreasing their in vivo reconstituting ability. We previously developed a recombinant single-chain form of a naturally occurring murine hybrid cytokine of IL-7 and the β chain of hepatocyte growth factor (rIL-7/HGFβ) that stimulates the in vitro proliferation and/or differentiation of common lymphoid progenitors, pre-pro-B cells, and hematopoietic progenitor cells (day 12 spleen colony-forming units) in cultures of mouse BM. Here we used the rIL-7/HGFβ in culture to induce large numbers of HSCs from multiple cell sources, including unseparated BM cells, purified HSCs, CD45- BM cells, and embryonic stem cells. In each instance, most of the HSCs were in the G0 phase of the cell cycle and exhibited reduced oxidative stress, decreased apoptosis, and increased CXCR4 expression. Furthermore, when injected i.v., these HSCs migrated to BM, self-replicated, provided radioprotection, and established long-term hematopoietic reconstitution. These properties were amplified by injection of rIL-7/HGFβ directly into the BM cavity but not by treatment with rIL-7, rHGF, and/or rHGFβ.
authors.affiliation: Department of Immunology, University of Connecticut, Stem Cell Institute, School of Medicine, Health Center, Storrs, CT 06269, USA. laijun.lai@uconn.edu
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Irving
authors.initials: I
authors.lastname: Goldschneider
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005269:Femur; D006085:Graft Survival; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology*; D007267:Injections; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology; D016131:Lymphocyte Subsets / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D022423:Myeloid Cells / Q000166:cytology; D021122:Protein Subunits; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology
chemical_list: D016207:Cytokines; C553307:HGF protein, mouse; D015851:Interleukin-7; D021122:Protein Subunits; D011994:Recombinant Proteins; C576410:interleukin-7, mouse; D017228:Hepatocyte Growth Factor