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Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model.

Santiago-Osorio E, Ledesma-Martínez E, Aguiñiga-Sánchez I, Poblano-Pérez I, Weiss-Steider B, Montesinos-Montesinos JJ, Mora-García Mde L - Med Sci Monit Basic Res (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.

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.

No MeSH data available.


Related in: MedlinePlus

Survival analysis of lethally irradiated BALB/c mice receiving peripheral mononuclear cells mobilized by vehicle (PB-MNC of BALB/c-PBS), 0.1 g/mL of CasNa (PB-MNC of BALB/c-CasNa), or 5 mg/kg Plerixafor (PB-MNC of BALB/c-Plerixafor). Each group contains 5 mice. Kaplan-Meier analysis was performed over 22 weeks. * P<0.05 compared with BALB/c-PBS.
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f4-medscimonitbasicres-21-206: Survival analysis of lethally irradiated BALB/c mice receiving peripheral mononuclear cells mobilized by vehicle (PB-MNC of BALB/c-PBS), 0.1 g/mL of CasNa (PB-MNC of BALB/c-CasNa), or 5 mg/kg Plerixafor (PB-MNC of BALB/c-Plerixafor). Each group contains 5 mice. Kaplan-Meier analysis was performed over 22 weeks. * P<0.05 compared with BALB/c-PBS.

Mentions: The results show that CasNa and Plerixafor induced increase in the numbers of LSK cells and that they produce CFUs, which shows the presence of HSCs/HPCs. However, considering that the ultimate test of HSC functionality is their ability to rescue lethally irradiated individuals from death, MNCs mobilized to PB with CasNa, Plerixafor, or PBS alone were transplanted to lethally irradiated syngeneic mice (Figure 4). Of mice receiving grafts mobilized by CasNa, 40% survived to 20 weeks after transplantation. Interestingly, the engraftment of the cells mobilized by AMD3100 was significantly inferior to that of the cells mobilized by CasNa, with a survival rate of only 10% at 19 weeks, although the number of CFUs and LSK cells is comparable between treatments, even though Plerixafor mobilized more CFUs than CasNa. In contrast, mice receiving grafts mobilized by PBS alone died within 2 weeks, probably due to failure to reconstitute hematopoietic cells, as suggested by the much lower frequencies of CFUs and LSK cells then in the CasNa or AMD3100 treatments.


Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model.

Santiago-Osorio E, Ledesma-Martínez E, Aguiñiga-Sánchez I, Poblano-Pérez I, Weiss-Steider B, Montesinos-Montesinos JJ, Mora-García Mde L - Med Sci Monit Basic Res (2015)

Survival analysis of lethally irradiated BALB/c mice receiving peripheral mononuclear cells mobilized by vehicle (PB-MNC of BALB/c-PBS), 0.1 g/mL of CasNa (PB-MNC of BALB/c-CasNa), or 5 mg/kg Plerixafor (PB-MNC of BALB/c-Plerixafor). Each group contains 5 mice. Kaplan-Meier analysis was performed over 22 weeks. * P<0.05 compared with BALB/c-PBS.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590580&req=5

f4-medscimonitbasicres-21-206: Survival analysis of lethally irradiated BALB/c mice receiving peripheral mononuclear cells mobilized by vehicle (PB-MNC of BALB/c-PBS), 0.1 g/mL of CasNa (PB-MNC of BALB/c-CasNa), or 5 mg/kg Plerixafor (PB-MNC of BALB/c-Plerixafor). Each group contains 5 mice. Kaplan-Meier analysis was performed over 22 weeks. * P<0.05 compared with BALB/c-PBS.
Mentions: The results show that CasNa and Plerixafor induced increase in the numbers of LSK cells and that they produce CFUs, which shows the presence of HSCs/HPCs. However, considering that the ultimate test of HSC functionality is their ability to rescue lethally irradiated individuals from death, MNCs mobilized to PB with CasNa, Plerixafor, or PBS alone were transplanted to lethally irradiated syngeneic mice (Figure 4). Of mice receiving grafts mobilized by CasNa, 40% survived to 20 weeks after transplantation. Interestingly, the engraftment of the cells mobilized by AMD3100 was significantly inferior to that of the cells mobilized by CasNa, with a survival rate of only 10% at 19 weeks, although the number of CFUs and LSK cells is comparable between treatments, even though Plerixafor mobilized more CFUs than CasNa. In contrast, mice receiving grafts mobilized by PBS alone died within 2 weeks, probably due to failure to reconstitute hematopoietic cells, as suggested by the much lower frequencies of CFUs and LSK cells then in the CasNa or AMD3100 treatments.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES-Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.

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.

No MeSH data available.


Related in: MedlinePlus