Platelet-derived circulating soluble P-selectin is sufficient to induce hematopoietic stem cell mobilization

• Published in: Stem cell research & therapy 2023-10, Vol.14 (1), p.300-300, Article 300
• Main Authors: Wang, Tso-Fu, Liou, Yu-Shan, Yang, Shang-Hsien, Lin, Guan-Ling, Chiang, Ya-Wen, Lien, Te-Sheng, Li, Chi-Cheng, Wang, Jen-Hung, Chang, Hsin-Hou, Sun, Der-Shan
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Anticoagulants; Antigens; Blood platelets; Cell adhesion; Cell adhesion & migration; Cell lineage; Colony-stimulating factor; Consciousness; Enzyme-linked immunosorbent assay; Enzymes; Ethylenediaminetetraacetic acid; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - metabolism; Granulocyte Colony-Stimulating Factor - pharmacology; Hematology; Hematopoietic stem cell mobilization; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Humans; Laboratory animals; Leukocytes (granulocytic); Ligands; Male; Mice; Mice, Inbred C57BL; Neutrophils; P-selectin; P-Selectin - genetics; P-Selectin - metabolism; P-selectin glycoprotein ligand 1; Plasma; Plasma levels; Platelets; Proteins; Recombinant Proteins - pharmacology; Retention; Soluble P-selectin; Stem cell transplantation; Stem cells; Stromal cells; Transplantation
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-023-03527-w

Granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of hematopoietic stem cells (HSCs) is a well-established method to prepare HSCs for transplantation nowadays. A sufficient number of HSCs is critical for successful HSC transplantation. However, approximately 2-6% of healthy stem cell donors are G-CSF-poor mobilizers for unknown reasons; thus increasing the uncertainties of HSC transplantation. The mechanism underlining G-CSF-mediated HSC mobilization remains elusive, so detailed mechanisms and an enhanced HSC mobilization strategy are urgently needed. Evidence suggests that P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are one of the cell-cell adhesion ligand-receptor pairs for HSCs to keep contacting bone marrow (BM) stromal cells before being mobilized into circulation. This study hypothesized that blockage of PSGL-1 and P-selectin may disrupt HSC-stromal cell interaction and facilitate HSC mobilization. The plasma levels of soluble P-selectin (sP-sel) before and after G-CSF administration in humans and male C57BL/6J mice were analyzed using enzyme-linked immunosorbent assay. Male mice with P-selectin deficiency (Selp ) were further employed to investigate whether P-selectin is essential for G-CSF-induced HSC mobilization and determine which cell lineage is sP-sel derived from. Finally, wild-type mice were injected with either G-CSF or recombinant sP-sel to investigate whether sP-sel alone is sufficient for inducing HSC mobilization and whether it accomplishes this by binding to HSCs and disrupting their interaction with stromal cells in the BM. A significant increase in plasma sP-sel levels was observed in humans and mice following G-CSF administration. Treatments of G-CSF induced a decrease in the level of HSC mobilization in Selp mice compared with the wild-type (Selp ) controls. Additionally, the transfer of platelets derived from wild-type mice can ameliorate the defected HSC mobilization in the Selp recipients. G-CSF induces the release of sP-sel from platelets, which is sufficient to mobilize BM HSCs into the circulation of mice by disrupting the PSGL-1 and P-selectin interaction between HSCs and stromal cells. These results collectively suggested that P-selectin is a critical factor for G-CSF-induced HSC mobilization. sP-sel was identified as a novel endogenous HSC-mobilizing agent. sP-sel injections achieved a relatively faster and more convenient regimen to mobilize HSCs in mice than G-CSF. These findings may serve