Mesenchymal Stromal Cells for Sepsis in Horses

hock joint injection
hock injected with mesenchymal stromal cells (MSCs)
Intra-articular injection with activated MSCs such as vancomycin is a promising treatment for horses with joint sepsis. Amy Dragoo

At the 2022 Equine Regenerative Medicine and Orthobiologics Summit (ERMOS), Laurie Goodrich, DVM, PhD, DACVS, Director of the Orthopedic Research Center at Colorado State University, reported on the value of mesenchymal stromal cells (MSCs) in managing septic arthritis. Many studies have demonstrated that MSCs are immunomodulating, with autologous and allogenic cells having equivalent actions on inflammation and immune modulation. She added that an increased concentration of MSCs has a greater effect on decreasing inflammation.  

MSCs also exert antimicrobial actions through the secretion of peptides and paracrine recruitment of immune cells. Activation of MSCs with TLR agonists stimulates antimicrobial peptides. This leads to improved immune responses, such as increased bacterial phagocytosis by neutrophils and decreased lipopolysaccharide expression. Goodrich noted that several different inflammatory activators of MSCs can logarithmically reduce bacterial counts and biofilm formation.  

In a study on treating septic arthritis from Staphylococcus aureus, TLR-activated MSCs were administered intraarticularly (IA) into the tibiotarsal joint. There were two objectives: a) Evaluate if this can improve the clinical outcome, and b) determine if activated MSCs can decrease the bacterial bioburden and inflammatory biomarkers. 

Eight healthy horses were used in the study in which Staphylococcal aureus was injected into the tibiotarsal joint. Four horses served as controls and were injected IA with vancomycin. The four treated horses were injected IA with vancomycin plus TLR-MSCs. All horses also received intravenous gentamycin and phenylbutazone. The control horses were euthanized on Day 7 and the treated horses on Day 14. 

The control horses experienced higher pain scores and non-weight-bearing lameness compared to the treated horses, which were able to walk on the affected leg. 

Synovial fluid bacterial counts of the control horses were markedly elevated compared to the absence of bacteria within the MSC-treated synovial fluid. Synovial fluid of the control horses was cloudy compared to the clearer fluid of the treated horses. 

There were also differences in total protein, nucleated cells, glucose and lactate in the synovial fluid, with values from the treated horses much improved over the controls. 

Markers of inflammation—IL-6 and IL-18—were elevated in the control horses and not significantly in the treated horses. 

Gross pathology of the joints appeared quite different. More cartilage damage and inflammation were visible in the control group compared to the treated group. The control horses had more normal-appearing joint surfaces. 

Besides the significant and effective treatment of septic arthritis with TLR-activated MSCs in conjunction with an antibiotic, this combination treatment also eliminated multi-resistant Staph aureus in the septic joints. 

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