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Vol. 44. Núm. S2.
Páginas S299 (outubro 2022)
Vol. 44. Núm. S2.
Páginas S299 (outubro 2022)
Open Access
GRANULOCYTE-COLONY STIMULATING FACTOR (G-CSF) ENHANCES THE MOBILIZATION OF BONE MARROW-DERIVED MESENCHYMAL STEM CELLS IN THE PERIPHERAL BLOOD OF BALB/C MICE
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FS Silvaa,b, F Magalhães-Gamab,c, WLL Nevesb, NP Garciab, HNS Ibiapinab, AM Tarragôb,d, EB Leona, AG Costaa,b,d, A Malheiroa,b,d, ND Araújoa,b
a Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil
b Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, AM, Brazil
c Instituto René Rachou, Fundação Oswaldo Cruz (Fiocruz), Belo Horizonte, MG, Brazil
d Universidade do Estado do Amazonas (UEA), Manaus, Brazil
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Introduction

Mesenchymal stem cells (MSCs) have emerged in recent years as beneficial tools for cell therapy and autologous/allogeneic transplantation and their clinical harnessing considers the bone marrow (BM) and peripheral blood (PB). However, this requires a process of endogenous mobilization that offers a non-invasive alternative. Thus, granulocyte colony-stimulating factor (G-CSF) and AMD3100 (Plerixafor®) are well known and clinically approved to stimulate MSCs mobilization, but data on their potential activity in MSCs mobilization are still scarce.

Objective

Evaluate the influence of G-CSF and AMD3100 stimulation on MSCs mobilization from BM to PB in BALB/c mice.

Material and methods

For this study, 45 male BALB/c mice aged 3-4 weeks were used. They were divided into 5 groups: PBS+PBS control group (CG, n = 9), PBS+GCSF group (n = 9), PBS+AMD3100 group (n = 9), G-CSF+PBS group (n = 9) and G-CSF+AMD3100 group (n = 9). Pre-treatment was performed with intraperitoneal (i.p.) injections of phosphate-buffered saline (PBS, 160 μl/i.p.) or G-CSF (200 μg/kg/i.p.) for 4 consecutive days. On day 5 (D5), 24 hours after the last injection of PBS or G-CSF, mice were also injected with PBS or AMD3100 (5 mg/kg/i.p.). After 1 hour, BM and PB samples were subsequently collected. The mobilized CD14+CD73+CD90+CD105+ MSCs were then evaluated ex vivo using Flow Cytometry. Statistical analyzes were performed through GraphPad Prism (v.5) using One-way ANOVA test with Tukey's post-test.

Results and discussion

Based on this study, it was found that there were no statistically significant differences for MSCs mobilization in the BM in any of the studied groups; however, the PBS+AMD3100 group had the highest rate of MSCs enrichment within the BM. Notably, mice of the G-CSF+PBS group exhibited the highest rate of MSCs mobilization in the PB when compared to the CG (p < 0.0001), while the G-CSF+AMD3100 group showed no statistically significant difference for MSCs mobilization in PB. Furthermore, the mice of the PBS+G-CSF group and the PBS+AMD3100 group did not exhibit a significant increase in MSCs mobilization in the PB.

Conclusion

With these results, it is verified that the pre-treatment with G-CSF is the most suitable to induce the MSCs mobilization to PB in a dose-dependent manner. Our data demonstrated that AMD3100 proved not to be suitable for MSCs mobilization in both BM and PB.

Funding

FAPEAM, CAPES and CNPq.

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Hematology, Transfusion and Cell Therapy
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