AUTHOR=Salem Mohamed L. , El-Bakry Kadry A. , Moubark Eman H. , Sobh Ashraf , Khalil Sohaila M. 

TITLE=Beneficial Modulatory Effects of Treatment With Bone Marrow Lysate on Hematopoietic Stem Cells and Myeloid Cells in Tumor-Bearing Mice

JOURNAL=British Journal of Biomedical Science

VOLUME=Volume 79 - 2022

YEAR=2022

URL=https://www.frontierspartnerships.org/journals/british-journal-of-biomedical-science/articles/10.3389/bjbs.2022.10328

DOI=10.3389/bjbs.2022.10328

ISSN=2474-0896

ABSTRACT=Leukopenia is one of the major side effects of myelosuppressive chemotherapy such as CTX. We and others have used CTX either alone or in combination with G-CSF for mobilization of HSCs. This mobilization, however, can induce expansion of myeloid cells with immunosuppressive phenotype. This as a pilot study aimed to test whether BML, a rich source of growth factors, in particular after CTX treatment, can lower the expansion of myeloid cells with immunosuppressive phenotypes in tumor bearing mice without interfering with anti-tumor effects or mobilization of stem cells. CD1 mice were treated on day 0 with i.p. injection of EAC.  On day 7, the mice were i.p. injected with CTX followed by s.c. injection of G-CSF for 5 consecutive days, single s.c. injection of BM lysate or single i.v. injection of BM cells prepared from either naïve or CTX. On day 13, peripheral blood samples, tumor cells, BM cells and splenocytes were harvested and myeloid and stem cells were analyzed by flow cytometry. Treatment of EAC bearing mice with BML/PBS or BML/CTX did not interfere with the anti-tumor effect of CTX. EAC tumor per se increased the numbers of iPMN cells in both blood and spleen. Treatment with CTX further increased the number of these cells, which were decreased upon treatment with BML, in particular BML/CTX. Treatment with BML/PBS or BML/CTX increased the numbers of stem cells (C.Kit+Sca-1+) in BM; the effect of BML/CTX was higher, with no significant effect on the numbers of HSCs. The results of this pilot study proof the concept of the beneficial effects of BM lysate in increasing the numbers of stem cells, while decreasing the numbers of myeloid cells with immunosuppressive phenotype. Further studies are going to analyze the molecular components of these growth factors in BM lysate.