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ASC Therapy Promotes Bone Regeneration After Bacterial Infection

Review of “Adipose-Derived Stromal Cells Are Capable of Restoring Bone Regeneration After Post-Traumatic Osteomyelitis and Modulate B-Cell Response” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Decreased bone regeneration due to inflammatory processes after severe bacterial infections remains a common problem in orthopedic surgery and previous studies from researchers led by Björn Behr (Ruhr-Universität Bochum, Germany) found that dysregulated inflammatory responses hindered bone regeneration after debridement following bacterial infection [1, 2]. Specifically, the authors observed reduced levels of osteoblastogenesis and increased levels of osteoclastogenesis and elevated B‐cell activity. 

Now the team returns with a STEM CELLS Translational Medicine study that investigates the potential of adipose-derived mesenchymal stem cell (ASC) therapy to restore the regenerative capacity of bone defects post-infection [3]. The authors chose ASCs given their relative success in enhancing regenerative processes in the clinic [4], their ease of isolation, their ease of use [5], and their osteogenic differentiation capacity [6].

Wagner et al. locally applied ASCs following debridement of infected bones of a murine animal model and analyzed the results using a raft of complementary techniques. Encouragingly, ASC therapy induced a ten‐fold increase in new bone formation due to increase osteoblast proliferation, subsequently enhanced osteoblastogenesis, and increased angiogenesis. Furthermore, ASC therapy also decreased osteoclast activity, and therefore bone resorption, in a RANKL-dependent manner. Interestingly, the authors also discovered that ASC therapy also modulated adaptive immune responses through a reduction in B‐cell activity mediated by galectin‐9 (GAL9) and B‐cell activating factor (BAFF); however, T-cell and granulocyte number was not affected. 

Overall, this data proposes ASC therapy as an effective means to boost bone regeneration and healing after bacterial infection and provides further insight into the activity of stem cells within the inflamed bone. 

For more on ASC therapy and bone regeneration, stay tuned to the Stem Cells Portal!

References

  1. Wagner JM, Zöllner H, Wallner C, et al., Surgical Debridement Is Superior to Sole Antibiotic Therapy in a Novel Murine Posttraumatic Osteomyelitis Model. PLOS ONE 2016;11:e0149389.
  2. Wagner JM, Jaurich H, Wallner C, et al., Diminished bone regeneration after debridement of posttraumatic osteomyelitis is accompanied by altered cytokine levels, elevated B cell activity, and increased osteoclast activity. Journal of Orthopaedic Research 2017;35:2425-2434.
  3. Wagner JM, Reinkemeier F, Wallner C, et al., Adipose-Derived Stromal Cells Are Capable of Restoring Bone Regeneration After Post-Traumatic Osteomyelitis and Modulate B-Cell Response. STEM CELLS Translational Medicine 2019;8:1084-1091.
  4. Gimble JM, Adipose tissue-derived therapeutics. Expert Opinion on Biological Therapy 2003;3:705-713.
  5. Lin K, Matsubara Y, Masuda Y, et al., Characterization of adipose tissue-derived cells isolated with the Celution system. Cytotherapy 2008;10:417-426.
  6. Behr B, Tang C, Germann G, et al., Locally Applied Vascular Endothelial Growth Factor A Increases the Osteogenic Healing Capacity of Human Adipose-Derived Stem Cells by Promoting Osteogenic and Endothelial Differentiation. STEM CELLS 2011;29:286-296.