Regenerative orthopaedic has gained its popularity in the last 15-20 years. But it was 1990 when Dr Philippe Hernigou started his research which would last until 2013, when the results were published. Dr Hernigou is a French orthopaedic surgeon, a true pioneer in regenerative orthopaedics. He investigated almost 2,000 patients who had their own stem cells injected and were followed up for 12.5 years on average. And the results were ground-breaking, showing that injecting stem cells was safe and did not cause increased risk of cancer.
This publication allowed an advent of clinical regenerative orthopaedic. Stem cells clinics started appearing like mushrooms, particularly in the United States. Regenerative treatments found themselves in the middle of media frenzy with celebrities getting treatments in the spotlight.
In the meantime, many credible providers along with academic researchers have been conducting clinical and laboratory research and gathering evidence. Over last 15 years the technique, its clinical applications and guidelines have evolved, based on new research and new evidence.
Today we have enough evidence to say with confidence that regenerative orthopaedic should be a part of treatment algorithm in many musculoskeletal conditions.
Platelet Rich Plasma (PRP)
PRP is the best researched orthobiologic. The evidence has reached the highest level, i.e., meta-analysis. One of the most recent ones was published in 2021 in The Orthopaedic Journal of Sports Medicine. The authors included 21 randomised controlled studies (RCT) concerning knee osteoarthritis (OA). In conclusion they stated that “we found that the benefit of intra-articular PRP in the treatment of knee OA was clinically important when compared with intra-articular saline or corticosteroid solution injections”.
Another meta-analysis published in 2020 in the Clinical Rheumatology looked at 21 RCTs concerning knee OA and three RCTs concerning hip OA. The analysis confirmed beneficial effect in knee OA but less so in hip OA which accords clinical experience. Another interesting meta-analysis, published in 2020 in the Journal of Orthopaedic Surgery and Research looked into the RCTs comparing PRP and hyaluronic acid (HA). Twenty RCTs were analysed. The authors concluded that PRP was more efficacious and with less risk of adverse events. Meta-analysis concern not only knee OA.
The one published in 2021 analysed eight RCTs concerning rotator cuff tendinopathy. The authors concluded that “PRP is safe and more effective for long-term shoulder pain symptoms and shoulder function associated with injury to rotator cuff”. They also called for more robust studies better reporting the PRP preparations and injection technique. Other meta-analysis looked at PRP in the treatment of Carpal Tunnel Syndrome and discogenic lower back pain.
Both showed clinically relevant benefit of PRP injections. Randomised Controlled Trials concerning PRP treatments are numerous. As for 2021, 28 RCTs concerning knee OA were published, all of them showing the benefit of PRP injections. There were three RCTs concerning hip OA (two showing benefit), nine concerning shoulder (eight showing benefit), 13 concerning epicondylitis of which 12 showed benefit of PRP therapy. There was one concerning degenerative disc disease, one for facet joints and one for sacroiliac joint.
Mesenchymal Stem Cells
Let’s move on to the mesenchymal stem cells (MSC) research. The mesenchymal stem cells are derived in clinical orthopaedic practice either from bone marrow or from adipose (fat) tissue. In case of the former, stem cells are injected either as a bone marrow aspirate (BMA) or a bone marrow aspirate concentrate (BMAC). In case of the latter, in order to extract stem cells from the adipose tissue, an enzymatic reaction is required. Such advanced processing makes the stem cells a medicinal product and falls under different (and stricter) FDA and European regulations. The legal regulations and subsequent technical requirements make the whole process practically unavailable for clinics and remains the domain of academic and clinical research. The adipose tissue can be processed in much simpler way, allowed by FDA and European regulators but it is questionable whether such processed product contains any substantial number of stem cells. On the other hand, adipose tissue contains plenty of regeneratively potent cells and growth factors which make the product applicable in the regenerative orthopaedics. Most of the past research applies to mesenchymal stem cells derived from bone marrow (BMA or BMAC), however, there is a growing number of research focused on adipose tissue derived stem cells. The future will show which product will demonstrate better clinical features. It is also hoped and cautiously expected that the regulators such as FDA will change their stance on adipose derived stem cells and will ease their current regulations applied to the enzymatic processing of the fat tissue.
One of the first RCTs concerning bone marrow concentrate used for symptomatic knee OA was published by Dr Chris Centeno and collaborators in 2018 in the Journal of Translational Medicine. The study included 48 patients with grade II and III OA, who were followed up for two years. The study showed beneficial effect of BMA. The same author published a mid-term analysis of the RCT of the treatment of rotator cuff tears with BMAC. Fifty patients were included with two years follow up. The mid-term analysis showed that BMAC could be a useful alternative to other treatments. Dr Hernigou and his collaborators published a very interesting study in 2021. In a prospective RCT on 120 knees in 60 patients they compared subchondral (into the bone) and intra-articular injection of BMAC. The follow up time was 15 years. The results indicated the superiority of the subchondral injection over the intra-articular one. Twenty per cent of patients in the subchondral group required a knee replacement within 15 years compared to 70 per cent in the intra-articular group.
In 2020, American Society of Interventional Pain Physicians (ASIPP) published in the Pain Physician Journal their Position Statement regarding bone marrow concentrate (BMC) therapy in musculoskeletal disorders. The statement 2 states: “Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions”. In their statement 3, the author’s state: “Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by train physician with the appropriate precautions under image guidance utilising a sterile technique”.
In summary, orthobiologics have gained a well-deserved position in the musculoskeletal medicine as a new and promising non-invasive treatment applicable to many spine and musculoskeletal conditions. Every month witnesses new publications bringing more evidence, changing the practice and opening new perspectives for the future. There are excellent training opportunities across the world which hopefully will popularise the regenerative orthopaedics further. Thousands of satisfied patients are the best testimonial for the regenerative treatments provided by credible physicians.
Dr Zbigniew M Kirkor
This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.