Early systemic immune biomarkers predict bone regeneration after trauma

• Type of Material: Article
• Authors: Albert Cheng, Georgia Institute of Technology; Casey E Vantucci, Georgia Institute of Technology; Laxminarayanan Krishnan, Georgia Institute of Technology; Marissa A Ruehle, Georgia Institute of Technology; Theresa Kotanchek, Evolved Analyt LLC; Levi B Wood, Georgia Institute of Technology; Krishnendu Roy, Emory University; Robert Guldberg, Emory University
• Language: English
• Date: 2021-02-23
• Publisher: NATL ACAD SCIENCES
• Publication Version: Final Published Version
• Copyright Statement: © 2021. Published under the PNAS license.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.2017889118
• Title of Journal or Parent Work: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• Volume: 118
• Issue: 8
• Keywords: PERSISTENT INFLAMMATION; immune dysregulation; ENHANCE; Science & Technology - Other Topics; DELIVERY; trauma; IMMUNOSUPPRESSION; CALLUS; L-ARGININE; INJURED PATIENTS; METABOLISM; SUPPRESSOR-CELLS; myeloid-derived suppressor cell; Science & Technology; Multidisciplinary Sciences; MECHANISMS; bone regeneration

Abstract

Severe traumatic injuries are a widespread and challenging clinical problem, and yet the factors that drive successful healing and restoration of function are still not well understood. One recently identified risk factor for poor healing outcomes is a dysregulated immune response following injury. In a preclinical model of orthopedic trauma, we demonstrate that distinct systemic immune profiles are correlated with impaired bone regeneration. Most notably, elevated blood levels of myeloid-derived suppressor cells (MDSCs) and the immunosuppressive cytokine interleukin-10 (IL-10) are negatively correlated with functional bone regeneration as early as 1 wk posttreatment. Nonlinear multivariate regression also implicated these two factors as the most influential in predictive computational models. These results support a significant relationship between early systemic immune responses to trauma and subsequent local bone regeneration and indicate that elevated circulating levels of MDSCs and IL-10 may be predictive of poor functional healing outcomes and represent novel targets for immunotherapeutic intervention.