Purinergic signaling in bone marrow stem cell mobilization
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Purinergic signaling in bone marrow stem cell mobilization Pranela Rameshwar 1 Received: 23 August 2020 / Accepted: 26 August 2020 # Springer Nature B.V. 2020
The paper by Cymer et al., “Pannexin-1 channel fuels by releasing ATP from bone marrow cells, a state of sterile inflammation required for optimal mobilization and homing of hematopoietic stem cells,” which is published in this issue of Purinergic Signalling, describes a novel method of sterile inflammation in stem cell mobilization. Interestingly, this study describes a dual role for pannexin-1, namely stem cell egress from bone marrow and homing into this organ. This double role for pannexin-1 channel makes this study novel because in general, a mobilizing agent moves cells from bone marrow into the periphery, but not the opposite. The authors used two known mobilizing agents, granulocyte-colony stimulating factor (G-CSF) and a CXCR4 inhibitor (AMD3100), to prove their main findings as the basis for their model system. Pannexin -1 forms small channels and is mostly linked to neurones, allowing for passage of ions and metabolites (1). Pannexin-1, through the release of ATP from bone marrow innate immune cells, establishes a sterile inflammatory environment to regulate the mobilization of HSC and other resident stem cells, including Mesenchymal stem cells (MSCs), endothelial progenitors, and very small embryonic-like (VSEL) stem cells. Pannexin-1 releases extracellular ATP (eATP) to induce a sterile inflammatory environment. Sterile inflammation, although carrying hallmarks of an infection, occurs independently of an infection, which may occur via the induction of danger-associated molecular patterns (DAMPs). This study also showed the release of mitochondrial DNA, which could also lead to sterile infection. Together, the findings underscore a complex mechanism of pannexin-1 function in stem cell mobilization. The dual roles for pannexin-1 are mediated by eATP. Interestingly, the two HSC mobilization agents, G-CSF and AMD3100, induce eATP, strongly suggesting that this could be an unknown mechanism of these agents, not previously reported. The role * Pranela Rameshwar [email protected] 1
Department of Medicine, Hematology/Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
for pannexin-1 was demonstrated indirectly with a small molecule inhibitor that inhibits the release of eATP. Ideally, this study requires molecular knockdown of pannexin-1 to determine if its mechanisms is redundant to related channels. Nonetheless, these findings, combined with the identification of inflammasome mediators, underscore the importance of sterile inflammation in harvesting bone marrow cells as well as to during transplant. The clinical relevance for this study is the contribution to the future of stem cell transplantation. HSC transplantation, has for many decades, utilized G-CSF to mobilize hematopoietic cell into the periphery, termed mobilized peripheral blood stem cells (MPB). Several days after injection of G-CSF, the stem cells are
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