Written by Mie, Southern Medical University
Review expert of this article: Professor Li Jing from the Affiliated Hospital of Jiangsu University
introduction
Recently, researchers from Rush University in Chicago published research results in the journal Arthroscopy, systematically evaluating the research on the treatment of knee osteoarthritis and cartilage defects by mesenchymal stem cells in the past 20 years. The results showed that mesenchymal stem cell therapy could significantly improve cartilage volume and improve patient function. Based on this meta-analysis, this article counted five clinical conclusions of mesenchymal stem cell therapy for osteoarthritis: mesenchymal stem cell therapy improves knee joint pain, mesenchymal stem cells can improve physical function, mesenchymal stem cells can improve cartilage volume, intra-articular injection of mesenchymal stem cells is a common clinical regimen, and the clinical effect depends on the concentration and dose of mesenchymal stem cells.
Osteoarthritis (OA) is a chronic degenerative disease related to aging, mainly due to articular cartilage damage, which can cause joint pain and decreased joint function in the affected population, and in severe cases, it will lead to physical disability and reduced quality of life. According to statistics, more than 500 million people worldwide suffer from osteoarthritis.
Currently, common treatments include:
(1) Drug treatment: non-steroidal anti-inflammatory drugs, opioids, recombinant human fibroblast growth factor, sodium hyaluronate, etc.;
(2) Surgical treatment: knee osteotomy, knee arthroplasty, etc.;
(3) TCM treatment;
(4) exercise therapy;
(5) Physical therapy, etc.
However, these treatment options can only alleviate the disease, but cannot reverse and restore the normal cartilage structure and function, and the disease will progress further, so it is necessary to constantly find new treatments.
In recent years, stem cells have shown great potential in the repair of articular cartilage damage, and there are also related mesenchymal stem cell (MSC) products on the market internationally, which are highly expected.
Mesenchymal stem cells have the potential for self-renewal, multidirectional differentiation and immune regulation, and are one of the potential therapies for the treatment of osteoarthritis. With the deepening of research, it has been found that mesenchymal stem cells mainly achieve the purpose of treating osteoarthritis through the following mechanisms:
Mechanism of mesenchymal stem cell therapy for osteoarthritis:
(1) Directed differentiation directly repairs damaged tissues. MSCs can differentiate into chondrocytes for cartilage repair.
(2) Paracrine factors regulate inflammatory responses, thereby promoting the self-repair ability of locally damaged tissues.
(3) Stem cells have homing characteristics, which can actively migrate to damaged joints under the action of the microenvironment in vivo and play a repair function.
Recently, researchers from Rush University in Chicago published research results in the journal Arthroscopy [1], systematically evaluating the research on the treatment of knee osteoarthritis and cartilage defects by MSC in the past 20 years. The results showed that MSC treatment could significantly improve cartilage volume and improve patient function.
A total of 25 clinical studies were included in this study, of which three studies (12%) had a single-arm prospective design, nine studies (36%) had a non-randomized controlled design, and 13 studies (52%) had a randomized controlled trial.
In the included studies, a total of 489 participants were treated with MSCs for osteoarthritis or knee cartilage defects. The total duration of final follow-up ranged from 1 week to 100 months, with an average of 8.3 years.
Conclusion 1: Mesenchymal stem cell therapy improves knee pain
A total of nine studies assessed the effect of MSC treatment on knee pain via a visual analogue scale (VAS). Further evaluation of the pain improvement in the MSC group and the MSC+ surgery group showed that MSC+ surgery had a more significant effect on improving knee pain than in the MSC group.
Differences in knee pain before and after treatment
Conclusion 2: Mesenchymal stem cells can improve physical function
Twenty-two studies reported functional outcome scores, of which seven studies and eight datasets compared functional improvement in the MSC treatment group (n = 161) and the control group (n = 164).
The results of the meta-analysis showed that MSC treatment improved the physical function and quality of life of patients. Further evaluation of the improvement of physical function in the MSC injection and MSC+ surgery group showed that the improvement of physical function in the MSC+ surgery group was better.
Differences in physical function before and after treatment
Conclusion 3: Mesenchymal stem cells can improve cartilage volume
Five studies reported changes in cartilage volume after MSC treatment. Meta-analysis found that cartilage volume was significantly improved in the MSC-treated group compared with the control group, but the changes in cartilage quality need to be further explored.
Conclusion 4: Intra-articular injection of mesenchymal stem cells is a common clinical regimen
MSC treatment methods mainly include autologous and allogeneic intra-articular MSC injection, cartilage injection MSC, tibial high osteotomy injection MSC, etc., the most common is autologous and allogeneic intra-articular MSC injection, with a total of 18 items.
Screenshot of MSC treatment protocol section
Conclusion 5: The clinical effect depends on the concentration and dose of mesenchymal stem cells
Further, the authors concluded that differences in pain response depended on the concentration and dose of mesenchymal stem cells. Meta-analyses found that infusions of 25 million MSCs improved patients' pain measurement scores, but cell infusions above this dose did not improve patients' pain measurement scores, so the dose of 25 million cells may be optimal. Analysis of the cause may be the limited space in the knee joint, too many cells will cause cells to clump and die due to insufficient space.
However, in this meta-analysis, there are great differences in the composition and delivery of MSCs in the included studies, and there is no unified treatment regimen for MSCs, so it still needs to be explored and summarized in the future.
brief summary
A review of the literature shows that mesenchymal stem cells are effective and safe in the treatment of osteoarthritis. After mesenchymal stem cell intervention, the patient's joint pain and physical function were improved, and mesenchymal stem cell therapy could significantly improve cartilage volume. However, clinically, the clinical results obtained by different research teams and different treatment regimens may vary due to the lack of uniformity in treatment factors (e.g., type of mesenchymal stem cells, site of origin), administration technique, concomitant procedure (i.e., HTO or microfracture) and concomitant injection (i.e., hyaluronic acid, PRP). In the future, when using mesenchymal stem cells in the treatment of osteoarthritis in clinical practice, a professional team is still needed to further specialize in finding the best treatment plan to help patients achieve better clinical outcomes.
Bibliography:
[1] Maheshwer B, Polce EM, Paul K, et al. Regenerative Potential of Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis and Chondral Defects: A Systematic Review and Meta-analysis. Arthroscopy. 2021; 37(1):362-378. doi:10.1016/j.arthro.2020.05.037