Sphingosine 1-Phosphate Signaling and Its Pharmacological Modulation in Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Allogeneic haemopoietic stem cell transplantation (HSCT) is increasingly used to treat haematological malignant diseases via the graft-versus-leukaemia (GvL) or graft-versus-tumour effects. Although improvements in infectious disease prophylaxis, immunosuppressive treatments, supportive care, and molecular based tissue typing have contributed to enhanced outcomes, acute graft-versus-host disease and other transplant related complications still contribute to high mortality and significantly limit the more widespread use of HSCT. Sphingosine 1-phosphate (S1P) is a zwitterionic lysophospholipid that has been implicated as a crucial signaling regulator in many physiological and pathophysiological processes including multiple cell types such as macrophages, dendritic cells, T cells, T regulatory cells and endothelial cells. Recent data suggested important roles for S1P signaling in engraftment, graft-versus-host disease (GvHD), GvL and other processes that occur during and after HSCT. Based on such data, pharmacological intervention via S1P modulation may have the potential to improve patient outcome by regulating GvHD and enhancing engraftment while permitting effective GvL.

Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation

“…To the best of our knowledge, this is the first report documenting the role of the neutrophil S1PR2/3 axis in organ transplantation. Others have shown that treatment with FTY720 (fingolimod) targeting S1PR1 prevented T cell egress from lymph nodes in cardiac, kidney, and hematopoietic cell transplant models ( 37 – 39 ). In addition, the function of S1PRs may be cell type specific.…”

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

“…In a human phase II trial, cannabidiol was also able to prevent aGvHD [239]#. The broad S1P 1 agonist, fingolimod, is approved for the treatment of multiple sclerosis and works by sequestering lymphocytes in secondary lymphoid organs [240]#. A more specific agonist (CYM-5442) was shown to reduce the severity of murine aGvHD by inhibiting macrophage recruitment via a reduction of CCL2 and CCL7 expression on endothelial cells [241].…”

The Efficacy of Stem Cells in Wound Healing: A Systematic Review

“…Numerous chemical and natural compounds have been identified for their potential to enhance the migratory capabilities of cells while maintaining their regenerative potential and differentiation capacity [ 40 , 86 ]. Chemical compounds like sphingosine-1-phosphate (S1P) and stromal cell-derived factor-1 (SDF-1) have shown promise in promoting cell migration by activating specific signaling pathways involved in cell movement, such as the PI3K/Akt and MAPK pathways [ 87 ]. Additionally, natural compounds such as epigallocatechin-3-gallate (EGCG) found in green tea and curcumin derived from turmeric have demonstrated the ability to modulate cell migration through their anti-inflammatory and antioxidant properties without compromising stem cell identity [ 88 ].…”