Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation
| Autor: | Sid Ganguly, Soumen Paul, Joseph McGuirk, Jonathan D. Mahnken, Brea Lipe, Maegan L. Capitano, Dennis Allin, Hal E. Broxmeyer, Amanda L. Wise, Leyla Shune, Anurag K. Singh, Sunil Abhyankar, Abigale Berry, George A. Vielhauer, Mary J. Laughlin, Omar S. Aljitawi, Christopher Lominska, Tara L. Lin, Avishek Ganguly, Amy Cantilena |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
education.field_of_study Umbilical Cord Blood Transplantation business.industry Immunology Population Cell Biology Hematology Cord Blood Stem Cell Transplantation Biochemistry Erythropoietin receptor 03 medical and health sciences Haematopoiesis fluids and secretions 030104 developmental biology Erythropoietin embryonic structures medicine Cancer research Progenitor cell education business medicine.drug Homing (hematopoietic) |
| Zdroj: | Blood. 128:3000-3010 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34+ cells. A significant population of UCB CD34+ HSPC expresses cell surface EPOR. Exposure of UCB CD34+ HSPC to EPO inhibits their migration and enhances erythroid differentiation. This migratory inhibitory effect was reversed by depleting EPOR expression on HSPC. Moreover, systemic reduction in EPO levels by hyperbaric oxygen (HBO) used in a preclinical mouse model and in a pilot clinical trial promoted homing of transplanted UCB CD34+ HSPC to BM. Such a systemic reduction of EPO in the host enhanced myeloid differentiation and improved BM homing of UCB CD34+ cells, an effect that was overcome with exogenous EPO administration. Of clinical relevance, HBO therapy before human UCB transplantation was well-tolerated and resulted in transient reduction in EPO with encouraging engraftment rates and kinetics. Our studies indicate that systemic reduction of EPO levels in the host or blocking EPO-EPOR signaling may be an effective strategy to improve BM homing and engraftment after allogeneic UCB transplantation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT02099266). |
| Databáze: | OpenAIRE |
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