According to Sohu, CCTV's "approaching Science" once reported that a Ms. Qin, who had suffered from rheumatoid arthritis for 11 years, tried stem cell therapy with the mentality of trying stem cell therapy after failing to use various methods. Unexpectedly, the symptoms were significantly improved, and two years after the end of stem cell therapy, she got rid of the shackles of long-term use of hormone drugs and became a mother. 

According to the relevant survey data, rheumatoid arthritis can occur at any age. The average prevalence rate of rheumatoid arthritis in the world is about 0.2%-1.0%, and that in China (mainland) is about 0.42%.

What is rheumatoid arthritis?

Rheumatoid arthritis (RA) is a common chronic and autoimmune disease, which is mainly characterized by synovitis, progressive joint and bone destruction, resulting in joint swelling and pain, morning stiffness, joint bone damage, joint deformity and so on. If there is no timely and effective treatment, there is even a risk of disability in the later stage of the disease, which will have a great impact on the work and life of the patients. 

In addition to bone loss, inflammation and autoimmune response are also potential causes of rheumatoid arthritis progression. Mesenchymal stem cells have broad prospects in the clinical research and application of rheumatoid arthritis in the past decade because of their anti-inflammatory, immunomodulatory and regenerative properties.

How does rheumatoid arthritis occur? 

The occurrence of rheumatoid arthritis may be related to heredity, sex hormones, environmental factors and immune disorders. This disease is a Th17-driven disease, and the imbalance of Th17/Treg is the key factor of RA. At the same time, the ratio of M1/M2 macrophages in RA is greater than 1, which is related to higher erythrocyte sedimentation rate (ESR), CRP and more osteoclasts, which play a key role in bone resorption and joint destruction.

What are the traditional treatments for rheumatoid arthritis? 

At present, rheumatoid arthritis is mainly treated with drugs, and can also be treated with traditional Chinese medicine under the guidance of doctors, including antirheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and so on. However, at present, these methods can not cure the disease, but can only alleviate the symptoms, reduce the activity of the disease and improve the quality of life to a certain extent.

How do stem cells treat rheumatoid arthritis?

Mesenchymal stem cells (MSC) are a kind of pluripotent stem cells with extensive immunomodulatory properties, which can be isolated from bone marrow, adipose tissue, umbilical cord blood, umbilical cord, placenta, dental pulp and so on. At present, there are relatively many mesenchymal stem cell therapies approved in Asian countries, of which South Korea has approved four MSC therapies, while Japan and India have each approved one MSC therapy.

01、Why can mesenchymal stem cells treat rheumatoid arthritis?

（1）Mesenchymal stem cells have strong immunomodulatory and anti-inflammatory effects. Mesenchymal stem cells can regulate the local environment and activate endogenous progenitor cells by intercellular interaction and secretion of a variety of factors, thus repairing damaged tissue. 

Due to the functional changes of regulatory T cells (Tregs) in patients with rheumatoid arthritis, mesenchymal stem cells can not only increase the production of Treg cells, but also produce interleukin-10 (IL-10) or transforming growth factor-β 1 (TGF-β 1), thus enhance their immunosuppressive ability and maintain their phenotype and function. 

In addition, mesenchymal stem cells reduce the acute or chronic activation of these cells in rheumatoid arthritis by inhibiting effector memory Th17 cells and secreting IL17-A. 

Therefore, MSC can not only inhibit the production of IL-17, but also induce immunopathogenic memory Th17 cells, which can be reprogrammed into T cells with regulatory phenotype and function, which plays an important role in tissue repair and remodeling.

（2）Mesenchymal stem cells have the characteristic of regeneration and can be used to repair solid tissues and organs by differentiating into mesenchymal tissue lineages (including mesenchymal stem cells-osteoblasts-osteocytes and mesenchymal stem cells-chondroblasts-chondrocytes). 

Studies have shown that mesenchymal stem cells can indirectly promote bone regeneration and enhance bone healing by inhibiting the function of osteoclasts. Extracellular vesicles derived from mesenchymal stem cells (MSC-EV) have been proved to enhance bone formation such as type I collagen (COLI) alkaline phosphatase (ALP) osteocalcin (OCN) and osteopontin (OPN). It can also inhibit osteoclast formation through osteoprotegerin (OPG)-RANKL-RANK signal pathway and indirectly promote bone tissue formation.

02、Clinical research

The main results were as follows: (1) in 2019, 9 patients with refractory rheumatoid arthritis received intravenous injection of autologous bone marrow mesenchymal stem cells and were followed up for 12 months. The range of motion score (DAS28), visual analogue scale (VAS) and erythrocyte sedimentation rate (ESR) of 28 joints decreased significantly after transplantation, and no adverse events were observed. These results show that autologous bone marrow mesenchymal stem cell transplantation can alleviate the disease activity of refractory rheumatoid arthritis. 

(2) 136patients received intravenous injection of umbilical cord mesenchymal stem cells (UC MSCs) combined with traditional DMARDs therapy. Within 12 hours of treatment, some patients' clinical symptoms such as joint pain, swelling and stiffness were relieved, and there were no serious side effects during and after infusion. These results show that umbilical cord mesenchymal stem cells have safety and rapid clinical response in the treatment of active rheumatoid arthritis.

Summary.

Mesenchymal stem cells are expected to become a new choice for the treatment of rheumatoid arthritis in the future because of their advantages of anti-inflammation, self-repair and immune regulation, which can significantly improve the clinical symptoms, improve the quality of life and prevent the progression of rheumatoid arthritis.