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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 mononuclear cells of bone marrow of health BALB/c mice (BM-MNC of BALB/c) or bone marrow of surviving Balb/c mice transplanted with peripheral MNC mobilized by CasNa. (Figure 4). Each group contains 5 mice. Kaplan-Meier analysis.
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f6-medscimonitbasicres-21-206: Survival analysis of lethally irradiated Balb/c mice receiving mononuclear cells of bone marrow of health BALB/c mice (BM-MNC of BALB/c) or bone marrow of surviving Balb/c mice transplanted with peripheral MNC mobilized by CasNa. (Figure 4). Each group contains 5 mice. Kaplan-Meier analysis.

Mentions: The enhanced survival at 20 weeks suggested HSC engraftment and hematopoietic reconstitution. To verify the latter, we analyzed whether the BM of the survivors (22 weeks after being irradiated and transplanted with MNCs mobilized to PB with CasNa) contained HPCs, as a criterion for hematopoietic reconstitution following the transplant. Notably, MNCs of BM from survivors of first transplant have the ability to form colonies of all lineages (granulocytes, macrophages, erythroid, granulocyte-macrophage, and mixed), which indicates repopulation of the bone marrow in irradiated mice. Indeed, we found a greater number of CFUs in surviving mice when compared with the number of CFUs from healthy mice of the same age (Figure 5). Next, we analyzed whether MNCs from BM of surviving mice had the ability to rescue a new group of lethally irradiated mice from death, and we found that 20% of mice receiving grafts of MNCs from surviving mice were still alive after 25 weeks, but mice transfused with MNCs from the BM of untreated mice of the same aged died at 2 weeks (Figure 6). This suggests that CasNa effectively induces functional HSC mobilization into PB.


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 mononuclear cells of bone marrow of health BALB/c mice (BM-MNC of BALB/c) or bone marrow of surviving Balb/c mice transplanted with peripheral MNC mobilized by CasNa. (Figure 4). Each group contains 5 mice. Kaplan-Meier analysis.
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Related In: Results  -  Collection

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

f6-medscimonitbasicres-21-206: Survival analysis of lethally irradiated Balb/c mice receiving mononuclear cells of bone marrow of health BALB/c mice (BM-MNC of BALB/c) or bone marrow of surviving Balb/c mice transplanted with peripheral MNC mobilized by CasNa. (Figure 4). Each group contains 5 mice. Kaplan-Meier analysis.
Mentions: The enhanced survival at 20 weeks suggested HSC engraftment and hematopoietic reconstitution. To verify the latter, we analyzed whether the BM of the survivors (22 weeks after being irradiated and transplanted with MNCs mobilized to PB with CasNa) contained HPCs, as a criterion for hematopoietic reconstitution following the transplant. Notably, MNCs of BM from survivors of first transplant have the ability to form colonies of all lineages (granulocytes, macrophages, erythroid, granulocyte-macrophage, and mixed), which indicates repopulation of the bone marrow in irradiated mice. Indeed, we found a greater number of CFUs in surviving mice when compared with the number of CFUs from healthy mice of the same age (Figure 5). Next, we analyzed whether MNCs from BM of surviving mice had the ability to rescue a new group of lethally irradiated mice from death, and we found that 20% of mice receiving grafts of MNCs from surviving mice were still alive after 25 weeks, but mice transfused with MNCs from the BM of untreated mice of the same aged died at 2 weeks (Figure 6). This suggests that CasNa effectively induces functional HSC mobilization into PB.

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