Stem cell knee injection shown to regenerate meniscus, reduce pain

Luciano Rodriguez, PhD

We read with great interest the manuscript from C. Thomas Vangsness Jr., MD, and colleagues. The randomized, double-blind controlled study was carried out at the appropriately high standard. They should methodologically add a reference with respect to cell count and product viability protocols pre-injection, as the use of cryopreserved cells involves thawing prior to injection. The post-thaw cell viability may be altered and it is always desirable to test viability and cell count prior to injection.

Human mesenchymal stem cells (MSCs) were delivered by intra-articular injection into the human knee in the 7-day to 10-day post-meniscectomy period. It might be interesting to discuss whether the injection of cells during the same surgical procedure, where the exposure of the remaining tissue in the joint is more recent, would favor implantation in the target area and thus the remedial effect.

The results demonstrate:

1. Safety of the treatment;
2. Reduction in the incidence of complications associated with meniscectomy in the groups treated with the investigational agent;
3. The therapeutic effect of MSCs seems to be multi-target; and
4. Immunological safety of intra-articular injection of allogeneic MSCs.

 

Ramon Cugat, MD, PhD
Orthopaedics Today Europe Editorial Board member
Fundación García Cugat for Biomedical Research
Instituto de Traumatología
Hospital Quirón Barcelona
Barcelona 

Thomas A. Einhorn, MD

Physicians and surgeons around the globe have expressed great hope that the use of stem cells will be the answer to many of the most challenging medical problems. In orthopaedics, it has been suggested that stem cells may be able to reverse osteoarthritis (OA) and degenerative disc disease, and treat fracture nonunion, avascular necrosis, articular cartilage injury and other conditions. However, while animal studies have produced preclinical data to support the use of stem cells in models of these conditions, few clinical reports provide the necessary evidence to fulfill the promise of stem cells in orthopaedics.

In the January 15, 2014 issue of the Journal of Bone and Joint Surgery, Vangsness and colleagues report their results of a randomized, double-blind, controlled study of the safety and efficacy of a simple intra-articular injection of human mesenchymal stem cells into the knee to promote meniscal regeneration following partial meniscectomy, and to modify existing osteoarthritic changes in the articular cartilage. Using two different doses of stem cells and a vehicle (hyaluronic acid) control, the authors demonstrated a statistically significant increase in meniscal volume as determined by MRI in 24% of patients in the low dose group and 6% in the high dose group. What was even more exciting was the finding that patients with osteoarthritic changes who received stem cell injections experienced a significant reduction in pain as measured on a visual analog scale. Since these are off-the-shelf allogeneic cells, if this effect can be shown to be reproducible, it could have a major impact in orthopaedics.

A few caveats must be mentioned to place the results of this study in its proper perspective. First, the study was funded by a commercial entity as opposed to a peer-reviewed federal agency or foundation. Second, while the study was effectively powered, the effects were still rather small (15% threshold) and there is no explanation given as to why results were better in the low dose as opposed to the high dose group. Finally, a major limitation of this study is that the distribution of the presence of OA across the groups was not controlled during enrollment. Since the effects on arthritic symptoms may be more important than the effects on meniscal regeneration, a follow-up study in which this issue is controlled would be beneficial.

One thing that is clear is that the field of stem cell biology and its impact on orthopaedics is now upon us. Additional studies are required to answer key questions, but the fact that high quality data now exist to support greater attention regarding the use of these cells is exciting.

Alberto Gobbi, MD

This randomized, double-blind, prospective study provided evidence on the ability of adult mesenchymal stem cells (MSCs) to promote meniscus regeneration following a subtotal meniscectomy and improve knee pain in patients presenting with concurrent osteoarthritis (OA). Additionally, there no adverse events or evidence of ectopic tissue formation were reported.

However, we should note that there are a few concerns on the possibly introduced bias by the small number of patients, meniscus regeneration measurements and the viability of the method. Although meniscus regeneration was significant, according to the performed statistical analysis, actually only 5 patients of 35 patients treated with the MSC injections presented with an increase of greater than 15% in meniscus volume in MRI controls at 1-year follow-up, while the number of these patients was reduced to 3 at 2-year follow-up (all 3 patients were from the subgroup that received injections of low-MSC-concentration).

Further level 1 studies are needed at medium-term follow-up, in larger series of patients, utilizing standardized MRI protocols on the quantification of the volume of meniscus regeneration and providing histological proof, if possible, to confirm the viability of the current treatment in meniscus regeneration. A dose response phenomenon should be also investigated, as patients treated with low-MSC-concentration injections presented better MRI findings.

The reported improvement in OA symptoms should be also investigated in larger level 1 studies, including homogeneous subgroups and objective data.