Mesenchymal stromal cells induce a permissive state in the bone marrow that enhances G-CSF-induced hematopoietic stem cell mobilization in mice

Experimental Hematology
Evert-Jan F M de KruijfMelissa van Pel

Abstract

Mesenchymal stromal cells (MSCs) support hematopoietic stem cells (HSCs) in vivo and enhance HSC engraftment and hematopoietic recovery upon cotransplantation with HSCs. These data have led to the hypothesis that MSCs may affect the HSC niche, leading to changes in HSC retention and trafficking. We studied the effect of MSC administration on the HSC compartment in the bone marrow (BM) in mice. After injection of MSCs, HSC numbers in the BM were decreased coinciding with an increased cell cycle activity compared with phosphate-buffered saline (PBS)-injected controls. Furthermore, the frequency of macrophages was significantly reduced and niche factors including Cxcl12, Scf, and Vcam were downregulated in endosteal cells. These BM changes are reminiscent of events associated with granulocyte colony-stimulating factor (G-CSF)-induced hematopoietic stem and progenitor cell (HSPC) mobilization. Interestingly, coadministration of MSCs and G-CSF resulted in a twofold increase in peripheral blood HSPC release compared with injection of G-CSF alone, whereas injection of MSCs alone did not induce HSPC mobilization. After intravenous administration, MSCs were only observed in the lungs, suggesting that they exert their effect on the HSC n...Continue Reading

Citations

Apr 23, 2019·Annals of the New York Academy of Sciences·Evert-Jan F M de KruijfMelissa van Pel
Dec 17, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Chunling XuGuanfang Su
Jan 4, 2020·Cell Biology and Toxicology·Dabin LeeJe-Yoel Cho
Aug 6, 2020·Frontiers in Cell and Developmental Biology·Rohan Kulkarni, Vaijayanti Kale
Jun 4, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Laura R Goldberg

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