Granulocyte-colony stimulating factor-mobilized mesenchymal stem cells: A new resource for rapid engraftment in hematopoietic stem cell transplantation

Abstract

The bone marrow (BM) microenvironment plays an important role in regulating hematopoietic stem cell self-renewal and differentiation. Mesenchymal stem cells (MSCs), which constitute approximately 0.01-0.0001% of the nucleated cells in the adult human BM, are an important component of the BM stroma that supports hematopoiesis. The BM stroma system is often damaged in patients who have undergone high-dose chemotherapy and/or radiation treatment. Thus, the BM stroma should be reconstructed during hematopoietic stem cell transplantation (HSCT). Granulocyte-colony stimulating factor (G-CSF) is a potent hematopoietic cytokine that regulates neutrophil generation within the BM by modulating the mobility, proliferation and maturation of neutrophil progenitor cells. The results from our study here show that G-CSF markedly increased the number of donor-derived MSCs in the BM and the peripheral blood. Engraftment was faster in HSCTs with bone marrow that was treated with G-CSF (G-BM) or with G-BM- and G-CSF-treated peripheral blood stem cells compared to stead-state bone marrow (SS-BM). Based on these findings, we hypothesize that G-CSF-mobilized treatment of MSCs may accelerate engraftment in HSCT.