title: Immunological characterization of the early human fracture hematoma.
abstract: The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma. The early human fracture hematoma is characterized by maturation of granulocytes and migration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. Humoral immunity characteristics comprise high concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα, but also elevated concentration of anti-inflammatory cytokines, e.g., IL-1 receptor antagonist and IL-10. Furthermore, we found that cells of the fracture hematoma represent a source for key chemokines. Even under the bioenergetically restricted conditions that exist in the initial fracture hematoma, immune cells are not only present, but also survive, mature, function and migrate. They secrete a cytokine/chemokine cocktail that contributes to the onset of regeneration. We hypothesize that this specific microenvironment of the initial fracture hematoma is among the crucial factors that determine fracture healing.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany. paula.hoff@charite.de.|German Arthritis Research Center (DRFZ), 10117, Berlin, Germany. paula.hoff@charite.de.|Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353, Berlin, Germany. paula.hoff@charite.de.
authors.forename: Paula
authors.identifier: 0000-0001-7494-0845
authors.initials: P
authors.lastname: Hoff
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.|German Arthritis Research Center (DRFZ), 10117, Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gaber
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.|German Arthritis Research Center (DRFZ), 10117, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Strehl
authors.affiliation: Julius Wolff Institute, Charité University Hospital, 13353, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schmidt-Bleek
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.|German Arthritis Research Center (DRFZ), 10117, Berlin, Germany.|Berlin-Brandenburg School for Regenerative Therapies (BSRT), 13353, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.|German Arthritis Research Center (DRFZ), 10117, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Huscher
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.|German Arthritis Research Center (DRFZ), 10117, Berlin, Germany.
authors.forename: G R
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Department of Orthopedics, University Hospital Heidelberg, 69118, Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schmidmaier
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353, Berlin, Germany.|Center for Musculoskeletal Surgery, Charité University Hospital, 10117, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Perka
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353, Berlin, Germany.|Julius Wolff Institute, Charité University Hospital, 13353, Berlin, Germany.
authors.forename: G N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany.|German Arthritis Research Center (DRFZ), 10117, Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Buttgereit
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001842:Bone and Bones / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D050723:Fractures, Bone / Q000276:immunology*; D006098:Granulocytes; D006406:Hematoma / Q000276:immunology*; D006801:Humans; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: Bone healing; Cytokines; Fracture healing; Fracture hematoma; Immune function; Inflammation