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Soluble factors differ in platelets derived from separate niches: a pilot study comparing the secretome of peripheral blood and bone marrow platelets
Institution:1. Elite Regenerative Stem Cell Specialists, LLC, Johnstown, Colorado, USA;2. R&D Regenerative Laboratory Resources, LLC, Johnstown, Colorado, USA;3. Colorado Spine Institute, PLLC, Johnstown, Colorado, USA;1. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA;2. Department of Pathology and Microbiology, Nebraska Medical Center, Omaha, Nebraska, USA;3. Division of Pathology and Laboratory Medicine, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio, USA;4. Masonic Cancer Center Biostatistics Core, University of Minnesota, Minneapolis, Minnesota, USA;5. Fate Therapeutics, San Diego, California, USA;6. Department of Medicine, Division of Hematology, Oncology, and Transplantation, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA;1. Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA;2. Ben Towne Center for Childhood Cancer Research, Seattle Children''s Research Institute, Seattle, Washington, USA;3. Department of Pediatrics, University of Washington, Seattle, Washington, USA;4. Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, UK;5. Translational Oncology, Allogene Therapeutics, San Francisco, California, USA;6. Department of Medicine, Division of Hematology/Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA;7. Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA;8. Division of Pediatric Hematology/Oncology, Boston Children''s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA;1. Liver Group, Institute for Liver and Digestive Health, Royal Free Campus, University College London, London, UK;2. Department of Biochemical Engineering, Advanced Centre for Biochemical Engineering, University College London, London, UK
Abstract:Background aimsPlatelet-rich plasma (PRP) and bone marrow aspirate are commonly used in orthobiologics for their anti-inflammatory, anabolic/regenerative and immunomodulatory characteristics via platelet degranulation and cell secretions. Although platelets are derived from megakaryocytes in the bone marrow, no attention has been paid to the potential benefits of bone marrow platelets and whether their contents differ from aging platelets in peripheral blood.MethodsIn the present study, leukocyte-poor peripheral blood-derived platelets in plasma (LPP) and leukocyte-poor bone marrow platelets in plasma (BMP) were prepared from six donors, activated with calcium chloride, incubated and sampled at day 0, day 3 and day 6. LPP and BMP are platelet preparations intended to evaluate the respective platelet secretomes but are not classified as conventional PRPs, as they are not concentrated to the extent necessary to meet the qualifying criteria. At each time point, 15 growth and immunomodulatory factors were quantitated in LPP and BMP: platelet-derived growth factor AA, basic fibroblast growth factor/fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, hepatocyte growth factor, macrophage colony-stimulating factor, stem cell factor, vascular endothelial growth factor, tumor necrosis factor alpha, IL-1β, interferon gamma, IL-4, IL-10, IL-1 receptor antagonist protein, IL-12p40 and arginase-1.ResultsThe results illustrate that platelets derived from bone marrow have a unique secretome profile compared with those derived from peripheral blood, with significant differences in anti-inflammatory cytokines, which are associated with monocyte polarization.ConclusionsUltimately, bone marrow-derived platelets may be useful as a stand-alone orthobiologic or as an effective adjuvant to autologous cell therapies where anti-inflammatory and anabolic processes are desired, especially with respect to monocyte function.
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