Induction of endogenous G-CSF for mobilization of hematopoietic stem cells for
DKMS Foundation (2019-2022).
Mobilization of cells from the bone marrow into the blood is currently the most commonly used strategy for obtaining hematopoietic stem cells (HSCs) for transplantation, but more efficient methods for obtaining HSC are still needed.
In previous mouse studies, we observed that cobalt protoporphyrin IX (CoPP) induces the mobilization of cells from the bone marrow into the blood by increasing the concentration of endogenous G-CSF in the blood. We have shown that CoPP mobilizes higher number of mature granulocytes and HSC and provides faster hematopoietic reconstitution after transplantation into irradiated mice compared to cells mobilized with recombinant G-CSF. At the same time, CoPP mobilizes fewer T lymphocytes than G-CSF. However, the question remains whether CoPP could be used for therapeutic purposes in humans and whether it could work better than recombinant G-CSF. Therefore, the project aims to characterize the clinically relevant properties of cells mobilized by CoPP. We will evaluate whether the administration of CoPP to humanized mice with a human hematopoietic system will allow effective mobilization of human granulocytes and HSC cells. We also plan to investigate whether a smaller number of T lymphocytes mobilized by CoPP will translate into a reduction of the GvHD.
This project will provide critical preclinical validation of CoPP as a potential new agent for HSC mobilization for subsequent transplantation. We hope to show that CoPP will be more effective than G-CSF in mobilizing human HSC, and that after a CoPP mobilized blood transplant, we will observe a lower frequency of GvHD.