Stem Cells Show Promise for Meniscal Tears

By John Gever, Senior Editor, MedPage Today

Published: February 10, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

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Action Points

• This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• This study suggests that patients receiving single injections of allographic mesenchymal stem cells one week after meniscectomy experienced reduced pain and less progression of knee osteoarthritis compared with patients receiving control injections.

SAN FRANCISCO -- Allogeneic mesenchymal stem cells (MSCs), injected into knee joints following surgery, appeared safe and showed signs of speeding the healing process in a two-year pilot trial, a researcher said here.

Patients receiving a single injection of 50 or 100 million MSCs one week after meniscectomy reported significantly less pain two years later, on average, compared with those receiving a placebo, according to C. Thomas Vangsness, MD, of the University of Southern California in Los Angeles.

A few patients in the low-dose MSC group also had evidence of meniscal regeneration in MRI scans after one year, although this effect was not seen with the higher dosage, he told attendees at the American Academy of Orthopaedic Surgeons' annual meeting.

Mesenchymal stem cells have become a hot topic in orthopedic repair, with some clinics already offering them to patients as a therapy. However, virtually all the published reports on these therapies have been uncontrolled case series.

Darren Johnson, MD, of the University of Kentucky in Lexington, told MedPage Today that the evidence base at this point is too scant to recommend such therapies to patients.

The therapy tested in the current trial involved a product called Chondrogen that consists of allogeneic MSCs, expanded in cell culture and injected along with hyaluronic acid.

Chondrogen is produced by Baltimore-based Osiris Therapeutics, which obtains the cells from young adults who donate bone marrow aspirates.

The multicenter study involved 55 adult patients with medial meniscal tears scheduled for surgical resection. Patients with grade III or IV osteoarthritis were excluded.

Participants were randomized to the two MSC doses mixed with a hyaluronic acid vehicle or to the vehicle alone. They were examined for pain response and had MRI scans of the resected knee periodically for up to two years afterward. All but three patients stayed in the study for the full two years.

As a phase I/II trial, it was primarily intended to demonstrate safety, and in that respect it was a big success, Vangsness said.

"That's the most important message," he said. "We've looked closely at injecting stem cells into the human joint and I think we can feel comfortable."

No ectopic or other unwanted tissue formation was seen in the study, alleviating one concern with the stem cell therapy. There also were no abnormalities on lab tests and no adverse events rated as serious or leading to study withdrawal.

Vangsness said the pain endpoint could become the primary efficacy outcome in future trials, which also should examine the effects of multiple injections.

Improvements from baseline in pain scores were seen in all three treatment arms, but the effect was larger in both MSC groups starting at six weeks. The difference grew as time went on.

At the two-year evaluation, the control group reported an approximately 20-mm improvement from baseline in a standard visual analog scale, compared with nearly 50 mm in the low-dose MSC group and about 45 mm with the higher dose.

Effects visualized with MRI were less impressive, however.

At the 12-month mark, 23.5% of patients receiving the low-dose MSC injection had an increase in meniscal volume of more than 15% from baseline, indicating significant regeneration. But only 5.6% of the high-dose group met this endpoint. None of the control group met it.

Only 18.2% of the low-dose group still met this endpoint at two years. No one in the high-dose or control groups met it.

On the other hand, Vangsness said, MRI evidence of osteoarthritis at the two-year evaluation was far more common in the control group than in the two MSC arms combined (21% versus 6%).

He also noted that the MRI knee scans proved to be "technically challenging" to perform and interpret.

One limitation to the study was that it did not include arthroscopic examinations.

"It was certainly impressive that there weren't any adverse events," said session co-moderator Diane Dahm, MD, of the Mayo Clinic in Rochester, Minn.

The other co-moderator, Keith Lawhorn, MD, of Fairfax, Va., said the study was important for moving the field of stem cell therapies forward.

"We're entering an exciting time for biologic therapies" in orthopedics, he said.

The trial was sponsored by Osiris.

Study authors and Dahm declared they had no relevant financial interests. Johnson reported relationships with Smith & Nephew. Lawhorn reported a relationship with Biomet.

Primary source: American Academy of Orthopaedic Surgeons
Source reference:
Vangsness C, et al "A randomized clinical trial using mesenchymal stem cells for meniscus regeneration and osteoarthritis" AAOS 2012; Abstract 552.