title: Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model.
abstract: BACKGROUND Hematopoietic stem cells transplantation has high clinical potential against a wide variety of hematologic, metabolic, and autoimmune diseases and solid tumors. Clinically, hematopoietic stem cells derived from peripheral blood are currently used more than those obtained from sources such as bone marrow. However, mobilizing agents used in the clinic tend to fail in high rates, making the number of mobilized cells insufficient for transplantation. We investigated whether sodium caseinate induces functional mobilization of hematopoietic stem cells into peripheral blood of Balb/c mice. MATERIAL AND METHODS Using a mouse model, we administrated sodium caseinate or Plerixafor, a commercial mobilizing agent, and analyzed counts of hematopoietic stem cells in peripheral blood, and then cells were transplanted into lethally irradiated mice to restore hematopoiesis. All assays were performed at least twice. RESULTS We found that sodium caseinate increases the number of mononuclear cells in peripheral blood with the immunophenotype of hematopoietic stem cells (0.2 to 0.5% LSK cells), allowing them to form colonies of various cell lineages in semisolid medium (p<0.05). This effect is similar to that of Plerixafor, and cells transplanted into lethally irradiated mice can restore hematopoiesis at higher percentages than mononuclear cells mobilized by Plerixafor (40% vs. 20%, respectively). Further, a secondary transplant rescued a separate group of irradiated mice from death, proving definitive evidence of hematopoietic reconstitution after hematopoietic stem cells transplantation. Data are presented as mean ± standard deviation. To determine significant differences between the data, one-way ANOVA and the Tukey test were used. CONCLUSIONS Collectively these results show the utility of sodium caseinate as a mobilizer of hematopoietic stem cells and its potential clinical application in transplantation settings.
authors.affiliation: Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: Edelmiro
authors.initials: E
authors.lastname: Santiago-Osorio
authors.affiliation: Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: Edgar
authors.initials: E
authors.lastname: Ledesma-Martínez
authors.affiliation: Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: Itzen
authors.initials: I
authors.lastname: Aguiñiga-Sánchez
authors.affiliation: Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Poblano-Pérez
authors.affiliation: Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: Benny
authors.initials: B
authors.lastname: Weiss-Steider
authors.affiliation: Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City, Mexico.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Montesinos-Montesinos
authors.affiliation: Immunobiology Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: María de Lourdes
authors.initials: Mde L
authors.lastname: Mora-García
mesh_terms: D000818:Animals; D001596:Benzylamines; D002364:Caseins / Q000494:pharmacology*; D000080027:Cyclams; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal
chemical_list: D001596:Benzylamines; D002364:Caseins; D000080027:Cyclams; D006571:Heterocyclic Compounds; C088327:plerixafor