Adipose‐Derived Stromal Cells Are Capable of Restoring Bone Regeneration After Post‐Traumatic Osteomyelitis and Modulate B‐Cell Response

• Published in: Stem cells translational medicine 2019-10, Vol.8 (10), p.1084-1091
• Main Authors: Wagner, Johannes Maximilian, Reinkemeier, Felix, Wallner, Christoph, Dadras, Mehran, Huber, Julika, Schmidt, Sonja Verena, Drysch, Marius, Dittfeld, Stephanie, Jaurich, Henriette, Becerikli, Mustafa, Becker, Kathrin, Rauch, Nicole, Duhan, Vikas, Lehnhardt, Marcus, Behr, Björn
• Format: Article
• Language: English
• Subjects: Adipose tissue; Administrative support; Animal models; Animals; Antibiotics; Bacterial infections; Bone growth; Bone healing; Bone marrow; Bone regeneration; Bone resorption; B‐cells; Computed tomography; Cytokines; Data analysis; Data collection; Defects; Flow cytometry; Fractures; Immune system; Immunohistochemistry; Immunomodulation; Infections; Inflammation; Innate immunity; Investigations; Lymphocytes B; Mesenchyme; Osteoblastogenesis; Osteoclastogenesis; Osteoclasts; Osteoimmunology; Osteomyelitis; Post‐traumatic osteomyelitis; Proteins; Regeneration; Rheumatoid arthritis; Stem cell transplantation; Stem cells; Stromal cells; Tissue Engineering and Regenerative Medicine
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.18-0266

Bone infections are a frequent cause for large bony defects with a reduced healing capacity. In previous findings, we could already show diminished healing capacity after bone infections, despite the absence of the causing agent, Staphylococcus aureus. Moreover, these bony defects showed reduced osteoblastogenesis and increased osteoclastogenesis, meaning elevated bone resorption ongoing with an elevated B‐cell activity. To overcome the negative effects of this postinfectious inflammatory state, we tried to use the regenerative capacity of mesenchymal stem cells derived from adipose tissue (adipose‐derived stem cells [ASCs]) to improve bone regeneration and moreover were curious about immunomodulation of applicated stem cells in this setting. Therefore, we used our established murine animal model and applicated ASCs locally after sufficient debridement of infected bones. Bone regeneration and resorption as well as immunological markers were investigated via histology, immunohistochemistry, Western blot, and fluorescence‐activated cell scanning (FACS) analysis and μ‐computed tomography (CT) analysis. Interestingly, ASCs were able to restore bone healing via elevation of osteoblastogenesis and downregulation of osteoclasts. Surprisingly, stem cells showed an impact on the innate immune system, downregulating B‐cell population. In summary, these data provide a fascinating new and innovative approach, supporting bone healing after bacterial infections and moreover gain insights into the complex ceremony of stem cell interaction in terms of bone infection and regeneration. Stem Cells Translational Medicine 2019;8:1084–1091 Adipose‐derived stem cells were capable of diminishing bone resorption and enhancing bone formation. Bone resorption was affected via downregulation of receptor activator of NF‐κB ligand and thereby osteoclast activity. Moreover, osteoblastogenesis was increased via upregulation of runt‐related transcription factor 2 levels. Besides bone regeneration, stem cells showed immunomodular abilities affecting innate immune system. More specifically, B‐cells were decreased via B‐cell activating factor and galectin‐9.