Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity
Within an aging population, fracture incidences will rise and with the augmented risks of impaired healing the overall risk of delayed bone regeneration will substantially increase in elderly patients. Thus, new strategies to rescue fracture healing in the elderly are highly warranted. Modulating th...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00713/full |
| _version_ | 1818027518585733120 |
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| author | Sebastian Wendler Sebastian Wendler Claudia Schlundt Claudia Schlundt Christian H. Bucher Christian H. Bucher Jan Birkigt Christian J. Schipp Hans-Dieter Volk Hans-Dieter Volk Georg N. Duda Georg N. Duda Georg N. Duda Katharina Schmidt-Bleek Katharina Schmidt-Bleek |
| author_facet | Sebastian Wendler Sebastian Wendler Claudia Schlundt Claudia Schlundt Christian H. Bucher Christian H. Bucher Jan Birkigt Christian J. Schipp Hans-Dieter Volk Hans-Dieter Volk Georg N. Duda Georg N. Duda Georg N. Duda Katharina Schmidt-Bleek Katharina Schmidt-Bleek |
| author_sort | Sebastian Wendler |
| collection | DOAJ |
| description | Within an aging population, fracture incidences will rise and with the augmented risks of impaired healing the overall risk of delayed bone regeneration will substantially increase in elderly patients. Thus, new strategies to rescue fracture healing in the elderly are highly warranted. Modulating the initial inflammatory phase toward a reduced pro-inflammation launches new treatment options for delayed or impaired healing specifically in the elderly. Here, we evaluated the capacity of the prostacyclin analog Iloprost to modulate the inflammatory phase toward a pro-regenerative milieu using in vitro as well as in vivo model systems. In vitro, Iloprost administration led to a downregulation of potential unfavorable CD8+ cytotoxic T cells as well as their pro-inflammatory cytokine secretion profile. Furthermore, Iloprost increased the mineralization capacity of osteogenic induced mesenchymal stromal cells through both direct as well as indirect cues. In an in vivo approach, Iloprost, embedded in a biphasic fibrin scaffold, decreased the pro-inflammatory and simultaneously enhanced the anti-inflammatory phase thereby improving bone healing outcome. Overall, our presented data confirms a possible strategy to modulate the early inflammatory phase in aged individuals toward a physiological healing by a downregulation of an excessive pro-inflammation that otherwise would impair healing. Further confirmation in phase I/II trials, however, is needed to validate the concept in a broader clinical evaluation. |
| first_indexed | 2024-12-10T04:49:10Z |
| format | Article |
| id | doaj.art-b69c8494f4c04433879052283cfee976 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T04:49:10Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b69c8494f4c04433879052283cfee9762022-12-22T02:01:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00713440179Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate ImmunitySebastian Wendler0Sebastian Wendler1Claudia Schlundt2Claudia Schlundt3Christian H. Bucher4Christian H. Bucher5Jan Birkigt6Christian J. Schipp7Hans-Dieter Volk8Hans-Dieter Volk9Georg N. Duda10Georg N. Duda11Georg N. Duda12Katharina Schmidt-Bleek13Katharina Schmidt-Bleek14Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité–Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité–Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité–Universitätsmedizin Berlin, Berlin, GermanyDepartment of Isotope Biogeochemistry, Helmholtz Centre for Environmental Research–UFZ, Leipzig, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité–Universitätsmedizin Berlin, Berlin, GermanyInstitute of Medical Immunology, Charité–Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité–Universitätsmedizin Berlin, Berlin, GermanyBerlin Institute of Health Center for Regenerative Therapies, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité–Universitätsmedizin Berlin, Berlin, GermanyWithin an aging population, fracture incidences will rise and with the augmented risks of impaired healing the overall risk of delayed bone regeneration will substantially increase in elderly patients. Thus, new strategies to rescue fracture healing in the elderly are highly warranted. Modulating the initial inflammatory phase toward a reduced pro-inflammation launches new treatment options for delayed or impaired healing specifically in the elderly. Here, we evaluated the capacity of the prostacyclin analog Iloprost to modulate the inflammatory phase toward a pro-regenerative milieu using in vitro as well as in vivo model systems. In vitro, Iloprost administration led to a downregulation of potential unfavorable CD8+ cytotoxic T cells as well as their pro-inflammatory cytokine secretion profile. Furthermore, Iloprost increased the mineralization capacity of osteogenic induced mesenchymal stromal cells through both direct as well as indirect cues. In an in vivo approach, Iloprost, embedded in a biphasic fibrin scaffold, decreased the pro-inflammatory and simultaneously enhanced the anti-inflammatory phase thereby improving bone healing outcome. Overall, our presented data confirms a possible strategy to modulate the early inflammatory phase in aged individuals toward a physiological healing by a downregulation of an excessive pro-inflammation that otherwise would impair healing. Further confirmation in phase I/II trials, however, is needed to validate the concept in a broader clinical evaluation.https://www.frontiersin.org/article/10.3389/fimmu.2019.00713/fullbone healingimmune modulationprostacyclin analogT cellmacrophageimmune cell |
| spellingShingle | Sebastian Wendler Sebastian Wendler Claudia Schlundt Claudia Schlundt Christian H. Bucher Christian H. Bucher Jan Birkigt Christian J. Schipp Hans-Dieter Volk Hans-Dieter Volk Georg N. Duda Georg N. Duda Georg N. Duda Katharina Schmidt-Bleek Katharina Schmidt-Bleek Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity Frontiers in Immunology bone healing immune modulation prostacyclin analog T cell macrophage immune cell |
| title | Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity |
| title_full | Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity |
| title_fullStr | Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity |
| title_full_unstemmed | Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity |
| title_short | Immune Modulation to Enhance Bone Healing—A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity |
| title_sort | immune modulation to enhance bone healing a new concept to induce bone using prostacyclin to locally modulate immunity |
| topic | bone healing immune modulation prostacyclin analog T cell macrophage immune cell |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00713/full |
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