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Patients undergoing anterior cruciate ligament (ACL) reconstruction with allografts appeared to heal more quickly when injections of bone marrow aspirate were included, according to a randomized trial.

Magnetic resonance imaging (MRI) scans at 3 months showed significantly higher signal intensity in the inferior third of the allograft for patients who received the stem cell-rich injections, relative to patients receiving sham injections with the allograft, reported Ophelie Lavoie-Gagné, a medical student at the University of California, San Diego.

Use of bone marrow aspirate was also associated with improved patient-reported outcomes and increased range of motion on physical exam, she said in a presentation at the Radiological Society of North America virtual meeting.

An allograft signal intensity score at 3 months was 17.67 in the bone marrow group vs 11.83 in the allograft-only control cohort (P=0.013), and signal intensity ratios were 2.73 and 1.88, respectively (P=0.04).

Lavoie-Gagné noted that the secondary outcome of range of motion also favored treatment with the bone marrow aspirate: at 9 months, flexion was 138° in that group vs 128° in the controls (P=0.02).

The patients receiving the bone marrow-aspirate also felt better, Lavoie-Gagné reported. On the Veterans Rand 12-item Mental Health survey, patients receiving bone marrow aspirate had a score of 57 compared with 54.7 among the controls (P=0.002) and on the International Knee Documentation Committee survey, patients on bone marrow aspirate had an average score of 64.2 vs 61.7 among the controls (P=0.04).

"Given the high incidence of ACL tears, management of this condition has significant consequences for athletes' return to play," she said. "ACL tears are common and devastating injuries among young athletes, and re-injury poses a significant threat to both successful return to play and long-term outcomes. Graft healing during ACL reconstruction is a slow process."

A total of 43 patients were enrolled in the study, with no significant differences in gender, age, or time to injury. Bone marrow aspirate was harvested from the anterior-superior iliac crest, concentrated via centrifuge, and injected into the allograft, and MRI was performed at 3 and 9 months postoperatively, Lavoie-Gagné said.

"A sham procedure was performed on the 23 control subjects," she told MedPage Today. "Both treatment and control groups received a small incision on the hip below the underwear line. In the treatment group, bone marrow was harvested from the iliac crest, and the blood was processed to concentrate the stem cells. The treatment group received stem cell injection into the ACL graft before it was placed into the knee, while the control group received a standard ACL graft without any stem cell injections."

"Our main finding was that patients receiving stem cell injection into the ACL graft demonstrated significantly more robust healing on MRI 3 months after surgery," Lavoie-Gagné said, noting that this is the first study to assess stem cell augmentation in ACL reconstruction.

"Given these results, it may have significantly positive influence on patients' clinical outcomes after surgery and ability to return to an active lifestyle," she said.

Asked for his perspective, Thomas Link, MD, PhD, of the University of California San Francisco School of Medicine, who was not involved with the study, explained: "It is known that ACL bone-patellar-bone allografts have worse outcome compared to autografts, so injection of bone marrow aspirate containing mesenchymal stem cells to improve ligamentization makes sense. The increased signal in the ACL that the authors found after bone marrow aspirate was injected could be related to increased vascularity and granulation tissue, indicating ligamentization, but gadolinium contrast was not injected to prove this."

"So overall this is an interesting study documenting a potential role of MRI to assess improved ligamentization after injection of bone marrow aspirate containing mesenchymal stem cells," he told MedPage Today. "Studies with longer follow-up, however, are required to also demonstrate better long-term outcomes and lower failure rates."