An Australian review has found “consistent evidence” for a beneficial effect of intra-articular stem cell injections on articular cartilage and subchondral bone, but not enough to recommend its use in the management of osteoarthritis.
The systematic review led by a team from Monash University found 13 mostly high-quality RCTs of mesenchymal stem cell (MSC) therapy but the heterogeneity across study populations, stem cell products, dose and frequency, control arms and outcome measures meant a meta-analysis was not possible.
Interventions included both allogeneic and autologous sources of cells – from bone marrow, umbilical cord, placenta, adipose tissue and peripheral blood. Most studies involved a single intra-articular injection but some protocols involved two or more injections at varying intervals.
Similarly there were many different structural outcome measures in the trials including cartilage volume/thickness, cartilage defects, quality and repair, meniscal volume and pathology, tibial bone area, bone marrow lesions, subchondral bone sclerosis and osteophyte formation, composite MRI scores and joint space width.
“There was consistent evidence that MSC treatment improved cartilage outcomes assessed from MRI, arthroscopy, or histology, and consistent evidence for beneficial effects on subchondral bone in populations at risk of OA,” said study authors, including Professor Flavia Cicuttini, Head of Rheumatology, Alfred Hospital.
“However, there were significant heterogeneity in injected MSCs, modest sample sizes, methodological limitations, and potential for publication bias.”
The review concluded more research was needed before mesenchymal stem cell therapy could be recommended.
TGA consumer advice is that the only proven safe and effective stem cell treatment is haematopoietic stem cell transplantation for the treatment of haematological disorders.
“Currently, no other stem cell treatment has been demonstrated to be safe and effective. However, some clinics located both in Australia and overseas offer unproven stem cell treatments,” it notes.
Rheumatologist Professor David Hunter – who was not involved in the study – agreed that while it was an area of promise, more rigorous research was required.
“The current evidence – both for trial quality and for heterogeneity of populations and outcomes – makes it impossible to draw meaningful conclusions and to recommend this therapy,” said Professor Hunter, who is chair of the Institute of Bone and Joint Research at the University of Sydney.
“My understanding is that stem cells are still widely used in the community. It is very difficult to know by how many people because this is so poorly regulated and it is largely out-of-pocket.”
He noted that a sizeable phase 3 clinical trial looking at the use of intra-articular stem cells in symptomatic knee osteoarthritis was about to commence recruitment in Sydney and Tasmania.
Dr Julien Freitag, a sports medicine physician and head of clinical research at the Melbourne Stem Cell Centre, told the limbic there was more evidence for the benefit of mesenchymal stem cells on OA pain and functional improvement.
“This paper has specifically said we are going to look at evidence of structural modification which is another big question. And despite the variability, the different source of cells, the dosing differences, the consistency of outcome is encouraging,” he said.
He noted the review included patients who were at risk of osteoarthritis.
“What we are looking to do is find an answer not just to symptomatic osteoarthritis but for the prevention of osteoarthritis.”
Dr Freitag, lead author of one of the clinical trials included in the review, said there was going to be an exponential increase in the need for total knee replacements.
“And even if TKR was a perfect operation, we don’t have the workforce to cover that type of exponential increase in surgery. ”
“People under 65 years are an enormous concern as they are 2.5 times more likely to need a revision knee replacement which has a far higher failure rate and complication rate. So we do need to find alternative options.”