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Commonly Used Orthopaedic Clinical Therapeutics Affect the Cytokine Activity of Culture-Expanded Mesenchymal Stem Cells

Commonly Used Orthopaedic Clinical Therapeutics Affect the Cytokine Activity of Culture-Expanded Mesenchymal Stem Cells

Jacob Giovanni Calcei, MD, UNITED STATES Tracey L Bonfield, PhD, UNITED STATES Ryan James Furdock, MD, UNITED STATES David Richard Fletcher, BS, UNITED STATES Evan Rudo, BS, UNITED STATES James E. Voos, MD

University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, UNITED STATES


2023 Congress   ePoster Presentation   2023 Congress   Not yet rated

 

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Summary: Exposure of human, bone marrow derived mesenchymal stem cells to commonly used orthopedic injectable therapies changes their cytokine profile.


Introduction

Hyaluronic acid (HA), platelet-rich plasma (PRP), and methylprednisolone are widely used to manage osteoarthritis (OA). More recently, human bone marrow derived mesenchymal stem cells (BM-MSCs) have garnered interest as a non-operative means for OA symptom modification. Anti-inflammatory cytokine secretion is a major component of BM-MSC action. We sought to describe the effect of HA, PRP, and methylprednisolone on the cytokine profile of BM-MSCs at multiple stages of culture expansion.

Methods

Nine BM-MSC cell lines from 4 human donors underwent three stages of culture expansion: passage 2 (P2), passage 3 (P3), and passage 4 (P4). Levels of OA-related cytokines (IL-1ß, IL-6, IL-8, IL-10, Stem cell Factor [SCF], Stem Cell Derived Factor-alpha [SDF-a]) were measured using Luminex multiplexing technology. The BM-MSC preparations were evaluated at each passage, 24 hours following exposure to HA, PRP, or methylprednisolone.

Results

Culture expansion altered cytokine production, however treatment with OA therapeutics further altered these responses implicating the potential of combined treatment of culture expanded hMSCs and OA therapeutics. Figure 1 demonstrates the behavior of cytokines after exposure to HA, PRP or methylprednisolone. Further, we tested different concentrations of the therapeutics to determine optimal dosing.

Exposure to increasing doses of HA reduced BM-MSC expression of SCF, SDF-a, VEGF, CCL20, and adiponectin (p<0.05 for all). PRP increased IL-1 levels in P2 and P3 (p<0.05 for both), IL-6 in P2 (100 pg/mL vs 5500 pg/mL, p<0.001), and IL-8 in P3 (900 pg/mL vs 3900 pg/mL, p<0.001). PRP did not affect IL-10 expression (p>0.05). Aside from an increase in IL-6 production for P2 (200 pg/mL vs 1500 pg/mL, p<0.05), methylprednisolone did not affect cytokine expression.

Conclusion

Orthopaedic adjuvants influence the inflammatory cytokine profile of BM-MSCs at multiple stages of culture expansion. These therapeutics have potential to be used with BM-MSCs to create an optimal cytokine environment for treatment of degenerative joint disease.


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