title: Identification of the chemokine CCL28 as a growth and survival factor for human hematopoietic stem and progenitor cells.
abstract: In an attempt to discover novel growth factors for hematopoietic stem and progenitor cells (HSPCs), we have assessed cytokine responses of cord blood (CB)-derived CD34(+) cells in a high-content growth factor screen. We identify the immunoregulatory chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor that directly stimulates proliferation of primitive hematopoietic cells from different ontogenetic origins. CCL28 enhances the functional progenitor cell content of cultured cells by stimulating cell cycling and induces gene expression changes associated with survival. Importantly, addition of CCL28 to cultures of purified putative hematopoietic stem cells (HSCs) significantly increases the ability of the cells to long-term repopulate immunodeficient mice compared with equivalent input numbers of fresh cells. Together, our findings identify CCL28 as a potent growth-promoting factor with the ability to support the in vitro and in vivo functional properties of cultured human hematopoietic cells.
authors.affiliation: Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Christine
authors.initials: C
authors.lastname: Karlsson
authors.forename: Aurélie
authors.initials: A
authors.lastname: Baudet
authors.forename: Natsumi
authors.initials: N
authors.lastname: Miharada
authors.forename: Shamit
authors.initials: S
authors.lastname: Soneji
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gupta
authors.forename: Mattias
authors.initials: M
authors.lastname: Magnusson
authors.forename: Tariq
authors.initials: T
authors.lastname: Enver
authors.forename: Göran
authors.initials: G
authors.lastname: Karlsson
authors.forename: Jonas
authors.initials: J
authors.lastname: Larsson
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: C414047:CCL28 protein, human; D019742:Chemokines, CC; D036341:Intercellular Signaling Peptides and Proteins