Stem Cell Therapy for Osteoarthritis

Osteoarthritis is a highly prevalent pain disorder involving erosion of articular cartilage and damage to subchondral bone and surrounding cell tissue. The avascularity of articular cartilage and limited regeneration of chondrocytes create limitations in self-healing. Current therapies include pharmacologic agents such as NSAIDs and opioids as well as surgical procedures such as joint replacements, none of which serve to reverse the damage to articular cartilage despite the complications they carry. Emerging evidence for the use of stem cell therapy for chondrogenesis has led to great interest and the opening of stem cell centers nationwide for the treatment of osteoarthritis. It is prudent to review the evidence thus far of the efficacy of these treatments to better inform our patients of their options.

The first generation of stem cell therapy involved bone marrow-derived mesenchymal stem cells (MSC), which were associated with donor site morbidity and pain and low cell number on harvest. These issues led to the investigation into alternative sources for MSCs, including periosteum, muscle, synovial membrane and adipose tissue. Since MSCs have the ability to differentiate into chondrocytes, osteoblasts, myoblasts, adipocytes and fibroblasts depending on the conditions under which they are stimulated, they offer great potential for tissue regeneration of various kinds.

Stromal vascular fraction (SVF) of adipose tissue has become the most popular substrate for the study of stem cell therapy for osteoarthritis, given that the stem cells contained within are abundant in number and easy to harvest. Despite concern that adipose derived mesenchymal stem cells (ADSCs) have limited chondrogenic potential, recent evidence demonstrate their ability to be induced along chondrocyte pathways under specific conditions, and animal models confirmed their chondrogenesis effect in vivo.

A metanalysis of human clinical studies on the effects of ADSCs on osteoarthritis was published earlier this year. All studies prepared ADSCs in the form of stromal vascular fraction (SVF), the component of lipoaspirate that contains ADSCs, pericytes, vascular adventitia cells, fibroblasts, preadipocytes, monocytes, macrophages and red blood cells. The 16 studies varied regarding site and time of SVF collection via liposuction, site of treatment (e.g. knees vs ankles), and whether the SVF was used with biologics such as platelet rich plasma (PRP) and fibrin.

All 16 studies reported favorable clinical outcomes, i.e. pain and function scores. 5 studies reported patient satisfaction rate, all of which were above 90%. 8 studies also reported radiological outcomes via MRI or X-ray, with mixed outcome measures showing an overall promising trend. MRI findings included improved cartilage thickness in most of the studies. Complication rates were reported in 7 studies, which were minor and included swelling at the procedural site.

The favorable clinical and radiographical outcomes shown in the metanalysis should be taken with a grain of salt, as there was high variability in all studies regarding data collected and use of biological adjuvants. This makes cross-study comparison difficult and leads to possible confounding of the actual weight of ADSCs’ effect. Biologics such as platelet rich plasma (PRP) have been shown to contain growth factors which potentially increase chondrocyte viability and differentiation, and may improve the synthetic capacity of MSCs. There was also significant variability in the methods used to prepare the ADSCs, as well as the methods for assessing chondrogenic potential of the harvested SVF. In the studies which reported it, the average percentage of ADSC in the SVF was only 9.2%, with the majority of the injectate being comprised of the other aforementioned SVF components. There was also great intra-study variability in the percentage of ADSC in SVF, with little analysis of possible factors contributing to this such as patient age or methods of preparation.

In summary, stem cell therapy in the treatment of osteoarthritis pain has shown promising results in early clinical trials, however these trials are limited by their lack of procedural standardization and potential biases. It will be worth following further investigations of this treatment modality as procedures are refined to introduce less variability.

References

Dubey NK, Mishra VK, Dubey R, Syed-Abdul S, Wang JR, Wang PD, Deng WP. Combating Osteoarthritis through Stem Cell Therapies by Rejuvenating Cartilage: A Review. Stem Cells Int. 2018 Mar 22;2018:5421019.

Hurley ET, Yasui Y, Gianakos AL, Seow D, Shimozono Y1, Kerkhoffs GMMJ, Kennedy JG. Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018 Apr 30.