Orthopedic injury therapy in rodents may soon be headed to the clinic

An interdisciplinary team of researchers at the University of Wisconsin–Madison has developed a promising new cell therapy with potential to improve tissue healing after orthopedic injuries.

The new cell therapy, recently described in the journal Stem Cells, accelerated the recovery of ruptured Achilles tendons in a rodent model, and may similarly aid other healing tissues, shortening the time until these structures regain functional strength.

The research team is now working to obtain FDA approval for a first human clinical trial to treat devastating injuries in musculoskeletal tissues.

The therapy works, says Ray Vanderby, professor of biomedical engineering and orthopedics and rehabilitation at UW–Madison, by using a particular cell type, called a macrophage, to orchestrate an improved wound-healing cascade. Macrophages have been implicated in the body’s inflammatory response, in limiting tissue damage, in promoting tissue repair and more.

To make these therapeutic macrophages, researchers expose a patient’s own macrophages to signaling factors from mesenchymal stromal cells, a cell type that exhibits stem cell-like qualities in that they give rise to several other types of cells, such as bone and muscle cells.

In the study, adding these specialized “exosome-educated macrophages” to healing Achilles tendons in rodents reduced scar tissue formation and accelerated functional recovery.

“In pre-clinical models our new approach is more consistent and significantly better than normal healing or surgical repair with mesenchymal stromal cells added,” Vanderby, a principal investigator on the study, explains.

Though not tested in the study, the method could improve outcomes for many problematic clinical issues, such as rotator cuff and anterior cruciate ligament (ACL) reconstructions. These surgeries restrict normal activity and often keep patients out of sports for roughly a year.

Faster healing may shorten rehabilitation and hasten a return to normal activities and sports, and a shorter recovery could help reduce overall health care costs, though the study does not address this.

Because this technology uses a patient’s own cells, the researchers say they expect the first clinical trials to begin in the near future.

The research team includes Connie S. Chamberlain, from the Department of Orthopedics and Rehabilitation; Peiman Hematti, from the Department of Medicine, Division of Hematology/Oncology; John A. Kink, from the UW Carbone Cancer Center, and others at the UW–Madison School of Medicine and Public Health.

Chamberlain, a research scientist, recently won an award for presenting this work at the 2019 Orthopaedic Research Society Conference, and the team has submitted a patent application based on the technology, filed by the Wisconsin Alumni Research Foundation.

“Use of these specialized macrophages has attracted interest at national conventions and has shown great promise as a new cell-based therapy for musculoskeletal healing,” Chamberlain says.