“Without a better understanding of what drives the initiation and progression of osteoarthritis, effective treatment has been limited,” said WFIRM lead author Johanna Bolander. “First, we learned what goes wrong in osteoarthritic joints, compared these processes to functional environments, and from this information
Osteoarthritis is a disease of the joint system. The joint synovial membrane – includes the connective tissue that covers the inner surface of the joint. The membrane functions to protect the joint and secretes a lubricating fluid filled with cellular elements necessary to maintain a healthy environment and ensure frictionless movement.
Stem Cell Therapy for Osteoarthritis
When injury occurs in healthy joints, the body recruits an army of inflammatory cells and sends them to the site of injury to help clean up the damaged tissue. In an arthrosis joint, traumatic injury leads to inflammation of the synovial membrane and cartilage damage.
“Inflammation worsens over time, leading to degradation of the cartilage that surrounds the bones of the joints and chronic inflammation in the surrounding tissues. For patients, this causes severe pain, swelling, and often limits daily activities,” said co-author Gary Poehling, MD. , an orthopedic surgeon at Atrium Health Wake Forest Baptist.
For this study, ed Advances in science, Journal of the American Association for the Advancement of Science, a research team set out to investigate what happens in the osteoarthritis joint environment that prevents the healing process from occurring.
“We assessed whether the cell population present in the joint fluid environment lacks the ability to contribute to functional tissue repair or whether there is something in the environment that impairs its ability to do so,” said WFIRM researcher Gustavo Moviglia, PhD.
The team isolated cells from the joint fluid of patients with osteoarthritis, separated the cells from the fluid, and examined them alone as well as in the presence of autologous fluid. Separated from the liquid, they found that the cells had the ability to undergo the processes necessary for functional tissue repair. When they added a small portion of the fluid to a cell culture assay, the cells’ abilities were compromised—they couldn’t do their job—suggesting that the specific osteoarthritis environment stopped them.
Based on these findings and what is known about functional tissue repair, cell therapies have been developed that can address the inflammatory environment and repair cartilage.
“Cartilage-activated immune cells that target inflammation, together with progenitor cells, promote tissue regeneration,” said Anthony Atala, MD, senior author and director of WFIRM. “It’s really a dynamic relationship between these two cell populations that’s so important for treatment efficacy.”
Cell fusion leads to the simultaneous treatment of several aspects involved in osteoarthritis: synovial inflammation, cartilage degradation, subchondral bone sclerosis and innervation of pain sensory neurons.
A compassionate use study was conducted in nine patients with established osteoarthritis who each received one or two injections to assess clinical efficacy. Efficacy was assessed by assessing pain and functional quality of life, MRI scans before and after treatment, and biopsies were obtained from one patient.
In addition, MRI studies confirmed cartilage regeneration. Further clinical studies are required to evaluate the outcome in a larger patient population, as well as to assess potential differences in patients in specific subgroups.
Additional co-authors: Maria Teresita Moviglia Brandolina, Olivia Jochl, Emma Parsons, and William Vaughan, all of WFIRM.
The study was partially funded by the Research Foundation – Flanders through research grant 1518618N, postdoctoral grant 12S6817N and the BAEF Henri Benedictus Fellowship. None of the authors have any competing interests to declare.