Bone-Marrow-Derived Macrophages Promising for Preventing OA

Osteoarthritis (OA) commonly affects horses, yet available therapies have only limited effect on clinical signs and disease progression. In fact, some even block healing mechanisms. Bone-marrow-derived macrophages, a type of white blood cell that produce the anti-inflammatory mediator interleukin-10 (IL-10), however, show promise as a novel OA treatment approach, said Bruno Menarim, DVM, PhD, during his presentation at the 2020 American Association of Equine Practitioners’ Convention, held virtually.

Menarim, currently at the University of Kentucky’s Gluck Equine Research Center, in Lexington, reminded his audience that inflammation of the joint’s inner lining, or synovitis, is a hallmark of OA. In the face of acute inflammation, macrophages residing in the joint proliferate and recruit more macrophages from marrow of the long bones nearby to respond to injury. Among other activities, these macrophages (especially the bone marrow macrophages) produce IL-10, resolve joint inflammation, and restore joint homeostasis by helping rebuild damaged tissues.

“If damage leading to this acute joint inflammation overwhelms the macrophages’ capacity to resolve it, then chronic inflammation and OA ensue,” said Menarim.

To help the “natural” population of macrophages that plays an integral role in acute inflammatory response to joint trauma, Menarim and colleagues from the Virginia-Maryland College of Veterinary Medicine looked at whether injecting macrophages from bone marrow aspirates could help resolve acute inflammation so it doesn’t become chronic, favoring OA development. To do this, the researchers studied six Thoroughbreds, inducing synovitis in both radiocarpal (upper knee) joints. Eight hours later they injected one of the radiocarpal joints and a hock joint (without synovitis) with 20 million nucleated cells isolated from an autologous (patient-specific) bone marrow aspirate. The bulk of those nucleated cells were macrophages.

The team collected synovial fluid from the treated and untreated knee joints as well as the treated hock joint on Days 1, 4, and 6 of the study.

“We found significantly lower levels of inflammation in synovial fluid and the joint lining in joints treated with the bone-marrow-derived mononuclear cells,” said Menarim. “We also found significantly higher concentrations of specific macrophages that produced high concentrations of IL-10 in the joint fluid.”

In addition to resolving acute joint inflammation, bone marrow mononuclear cells can serve as a practical point-of-care treatment for joint trauma, said Menarim. Veterinarians can collect and process the patient’s own bone marrow to isolate the macrophages/mononucleated cells in about three hours and freeze excess cells for further use.

“Since BMNCs do not interfere with healing mechanisms but actually promote them, BMNC therapy can provide long-lasting effects, extending the career and well-being of equine athletes as (it has been) observed in people,” said Menarim.